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Article in Chinese | WPRIM | ID: wpr-927891


Objective: To uncover the time-dependent expression pattern of ptk2b gene and ptk2b-encoded protein, protein tyrosine kinase 2 beta(PTK2B), in the brain tissues of transgenic animal models of Alzheimer's disease (AD) and its relationship with the levels of Aβ1-42, phosphorylation of Tau (p-Tau) and low density lipoprotein receptor-related protein-1(LRP-1) in blood and brain tissues. Methods: In this study, 5-, 10- and 15-month-old APPswe/PS1dE9 double-transgenic mice harboring the genotype of AD confirmed by the gene test were divided into the 5-, 10- and 15-month-old experiment groups, and simultaneously, age-matched C57BL/6J mice were placed into the corresponding control groups, with 8 mice in each group. All mice were subjected to the Morris Water Maze for test of cognitive and behavioral ability. Expression profiles of PTK2B, Aβ1-42, p-Tau/Tau and LRP-1 in the hippocampus or blood of mice were quantified by using the immunohistochemistry staining, Western blot or enzyme-linked immunosorbent assay (ELISA), while the mRNA expression of ptk2b in the hippocampus was quantified by using the real-time quantitative polymerase chain reaction (qRT-PCR). Results: Results of experiment groups demonstrated that as mice aged, the expression levels of PTK2B, ptk2b mRNA, Aβ1-42 and p-Tau/Tau in the hippocampus were increased, and the expression of LRP-1 was decreased gradually. While in the blood, the level of Aβ1-42 was decreased, and the cognitive and behavioral ability was decreased in an age-dependent manner (all P< 0.05). However, comparisons among the control groups, only the age-dependent downregulation of LRP-1 were observed in hippocampus(P<0.05), but other indicators had no significant differences (P>0.05). Conclusion: In the hippocampus of APP/PS1 double-transgenic mice, the expressions of PTK2B, Aβ1-42 and p-Tau/Tau are upregulated, LRP-1 is downregulated, while cognitive and behavioral ability is decreased, and such changes are presented in a time-dependent manner.

Alzheimer Disease/metabolism , Amyloid beta-Peptides , Amyloid beta-Protein Precursor/genetics , Animals , Focal Adhesion Kinase 2/metabolism , Hippocampus/metabolism , Low Density Lipoprotein Receptor-Related Protein-1 , Maze Learning , Mice , Mice, Inbred C57BL , Mice, Transgenic , RNA, Messenger
Article in Chinese | WPRIM | ID: wpr-921714


This study intended to explore the effect and mechanism of total flavonoids of Drynariae Rhizoma in improving scopola-mine-induced learning and memory impairments in model mice. Ninety four-month-old Kunming(KM) mice were randomly divided into six groups. The ones in the model group and blank group were treated with intragastric administration of normal saline, while those in the medication groups separately received the total flavonoids of Drynariae Rhizoma, Kangnaoshuai Capsules, donepezil, as well as total flavonoids of Rhizoma Drynariae plus estrogen receptor(ER) blocker by gavage. The mouse model of learning and memory impairments was established via intraperitoneal injection of scopolamine. Following the measurement of mouse learning and memory abilities in Morris water maze test, the hippocampal ERβ expression was detected by immunohistochemistry, and the expression levels of ERβ and phosphorylated p38(p-p38) in the hippocampus and B-cell lymphoma 2(Bcl-2), Bcl-2-associated death promoter(Bad), and cysteinyl aspartate-specific protease-3(caspase-3) in the apoptotic system were assayed by Western blot. The contents of malondia-ldehyde(MDA), superoxide dismutase(SOD), and nitric oxide(NO) in the hippocampus were then determined using corresponding kits. Compared with the control group, the model group exhibited significantly prolonged incubation period, reduced frequency of cros-sing the platform, shortened residence time in the target quadrant, lowered ERβ, Bcl-2 and SOD activity in the hippocampus, and increased p-p38/p38, Bad, caspase-3, MDA, and NO. Compared with the model group, the total flavonoids of Rhizoma Drynariae increased the expression of ERβ and SOD in the hippocampus, down-regulated the expression of neuronal pro-apoptotic proteins, up-re-gulated the expression of anti-apoptotic proteins, and reduced p-p38/p38, MDA, and NO. The effects of total flavonoids of Drynariae Rhizoma on the above indexes were reversed by ER blocker. It has been proved that the total flavonoids of Drynariae Rhizoma obviously alleviate scopolamine-induced learning and memory impairments in mice, which may be achieved by regulating the neuronal apoptotic system and oxidative stress via the ER-p38 mitogen-activated protein kinase(ER-p38 MAPK) signaling pathway.

Animals , Flavonoids , Hippocampus , Maze Learning , Mice , Polypodiaceae , Receptors, Estrogen , Scopolamine/toxicity , Signal Transduction , p38 Mitogen-Activated Protein Kinases/genetics
Braz. arch. biol. technol ; 64: e21200428, 2021. graf
Article in English | LILACS | ID: biblio-1153297


HIGHLIGHTS: Tumor progression and anxiety and depression behaviors under evaluation during propranolol use in murine melanoma. Evaluation of anxiety and depression through forced swimming behavior tests, elevated plus maze, open field and marble-burying test.

Abstract Melanoma, a severe form of skin cancer, has rapid growth and has been prone to behavioral disorders that worsen the patient's prognosis and survival. Among these psychic disorders can occur anxiety and depression, in addition to cognitive deficit. In order to try to elucidate the neuropsychological disorders that occur in melanoma, the objective of this study was to evaluate propranolol in tumor progression and in anxious and depressive behaviors in an animal model with melanoma. B16F10 cells were injected into C57BL6/J mice subsequently treated with propranolol at doses of 1.43 mg/kg and 5.71 mg/kg and evaluated for tumor growth and in open field, forced swimming, elevated plus maze and marble-burying test at initial time and consolidated tumor. As a result, the group treated with propranolol at a dose of 5.71 mg/kg showed less tumor growth. In the initial behavioral tests, melanoma altered the animals' motility, but anxious behavior was not detected. Depressive behavior was detected in the forced swimming test in the two doses of the treatment used. When taking time with consolidated tumor, there was a reduction in the locomotor activity of the animals in the open field test, impairing the analysis of anxious and depressive behavior. The data suggest that there was a reduction in the progression of melanoma, there was no anxious behavior in the animals, only the depressive behavior and the use of propranolol did not improve the evaluated behavior.

Animals , Male , Mice , Anxiety/psychology , Propranolol/administration & dosage , Skin Neoplasms/psychology , Melanoma, Experimental/psychology , Depression/psychology , Swimming , Maze Learning , Disease Models, Animal , Mice, Inbred C57BL
Braz. arch. biol. technol ; 63: e20200206, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132262


Abstract The high prevalence of anxiety disorders associated with pharmacotherapy side effects have motivated the search for new pharmacological agents. Species from Citrus genus, such as Citrus limon (sicilian lemon), have been used in folk medicine as a potential therapy to minimize emotional disorders. In order to searching for new effective treatments with fewer side effects, the present study evaluated the anxiolytic mechanism of action and the hypnotic-sedative activity from the Citrus limon fruit's peels essential oil (CLEO). Adults male Swiss mice were submitted to barbiturate-induced sleep test; elevated plus-maze (EPM) and light-dark box (LDB) (evaluation of the mechanism of action); rotarod; and catalepsy tests. CLEO oral treatment decreased latency and increased the sleep total time; moreover it induced in animals an increased the number of entries and percentage of time spent into open arms of the EPM; an increased the number of transitions and the percentage of time into light compartment in the LDB; which were only antagonized by flumazenil pretreatment, with no injury at motor function. Thus, results suggest that CLEO treatment induced an anxiolytic behavior suggestively modulated by the benzodiazepine binding site of the GABAA receptor or by an increase of GABAergic neurotransmission, without cause impairment in the motor coordination.

Animals , Male , Mice , Anxiety/drug therapy , Anti-Anxiety Agents/therapeutic use , Oils, Volatile/therapeutic use , Citrus/chemistry , GABA Modulators/pharmacology , Hypnotics and Sedatives/therapeutic use , Anti-Anxiety Agents/isolation & purification , Maze Learning/drug effects , Hypnotics and Sedatives/isolation & purification
Braz. arch. biol. technol ; 63: e20180379, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132267


Abstract Hippocampus is a part of the brain that has a major role in spatial learning and memory which can be affected by herbal extracts. Incense resin (Styrax benzoin) has been used by local communities to improve intelligence. However, there is no scientific evidence of the functions of Styrax benzoin for regulating hippocampal function. The aim of this study was intended to analyze and investigate the effect of incense resin on learning, memory, and dendrite complexity of mice. Three months old male Deutch Democratic Yokohama (DDY) mice were injected orally with graded doses of 100, 150, and 200 mg/kg of incense resin aqueous extract daily for 30 days. Spatial learning and memory performance levels were tested with Y-maze alternation, novel object recognition, and Morris water maze. The branches and maximum dendritic span in the dentate gyrus were observed by the Golgi-Cox staining. Overall, our results showed that incense resin extract increased learning and memory ability, and the number of dendrite branching in the dentate gyrus.

Animals , Male , Mice , Dendritic Cells/drug effects , Plant Extracts/pharmacology , Styrax/chemistry , Spatial Learning/drug effects , Memory/drug effects , Administration, Oral , Maze Learning/drug effects
Acta Physiologica Sinica ; (6): 777-784, 2020.
Article in Chinese | WPRIM | ID: wpr-878225


The objective of this study was to elucidate the effect of chronic stress (CS) on dopamine (DA) level and synaptic efficiency in the hippocampal dentate gyrus (DG) during spatial learning and memory. Sprague Dawley (SD) male rats were randomly divided into control group and CS group (n = 10). CS group was treated with chronic mild unpredictable stress, and control group did not receive any treatments. The levels of epinephrine and corticosterone (CORT) in serum were measured by using enzyme-linked immunosorbent assay (ELISA); the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test. Meanwhile, the amplitude of field excitatory postsynaptic potential (fEPSP) and concentration of DA in the DG region were determined by in vivo electrophysiology, microdialysis and HPLC techniques during MWM test in rats. After that, the DA D1 receptor (D1R) and its key downstream members in DG were examined by immunohistochemistry or Western blot assay. The results showed that the levels of epinephrine and CORT in the serum of the rats in CS group were significantly increased compared with those in the control group (P < 0.05). In CS group rats, the escape latency was significantly prolonged and the number of platform crossing was markedly decreased during MWM test, compared with those in control group (P < 0.05). Furthermore, the amplitude of fEPSP in the DG was not changed during MWM test in CS rats, while it was significantly increased on the 3rd day of MWM test in control group (P < 0.05). Compared with baseline or control group, CS group showed significantly increased DA level from the 1st to 3rd days of MWM test in the DG (P < 0.05). In addition, the protein expression of D1R was markedly up-regulated in the DG in CS group, while the protein expression levels of p-PKA, p-CREB and BDNF were significantly reduced, compared with those in control group. These results suggest that CS may impair spatial learning and memory abilities in rats through the enhancement of the DA levels in the hippocampal DG.

Animals , Dentate Gyrus , Dopamine , Hippocampus , Male , Maze Learning , Rats , Rats, Sprague-Dawley , Spatial Learning , Spatial Memory
Acta Physiologica Sinica ; (6): 463-474, 2020.
Article in Chinese | WPRIM | ID: wpr-827040


Formaldehyde is one of the simplest organic small molecules containing C, H and O elements in the early stage of earth's evolution; however, it has been found to be existed in every eukaryotic cell and participate in "one carbon metabolism". Recent studies have shown that formaldehyde may act as a signal molecule to regulate memory formation. After electrical stimulation or learning activity, the levels of formaldehyde in rat brains were increased instantly, and N-methyl-D-aspartate (NMDA) receptor was activated to promote the formation of long-term potentiation (LTP) or spatial memory. On the contrary, after reducing the levels of formaldehyde in the brains, NMDA receptor could not be activated, which was accompanied by the deficits in both LTP and memory. Moreover, in the brains of normal aged rats and APP/PS1 transgenic mice, the concentrations of formaldehyde were abnormally increased, which directly inhibited NMDA receptor activity and impaired spatial memory. This article reviewed the physiological and pathophysiological functions of endogenous formaldehyde in learning and memory.

Animals , Formaldehyde , Hippocampus , Long-Term Potentiation , Maze Learning , Memory , Memory Disorders , Mice , Rats , Receptors, N-Methyl-D-Aspartate
Braz. j. med. biol. res ; 53(10): e9861, 2020. graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132476


Fetal exposure to sevoflurane induces long-term cognitive impairment. Histone acetylation regulates the transcription of genes involved in memory formation. We investigated whether sevoflurane exposure during late-pregnancy induces neurocognitive impairment in offspring, and if this is related to histone acetylation dysfunction. We determined whether the effects could be reversed by an enriched environment (EE). Pregnant rats were exposed to 2.5% sevoflurane or control for 1, 3, or 6 h on gestational day 18 (G18). Sevoflurane reduced brain-derived neurotrophic factor (BDNF), acetyl histone H3 (Ac-H3), and Ac-H4 levels and increased histone deacetylases-2 (HDAC2) and HDAC3 levels in the hippocampus of the offspring on postnatal day 1 (P1) and P35. Long-term potentiation was inhibited, and spatial learning and memory were impaired in the 6-h sevoflurane group at P35. EE alleviated sevoflurane-induced cognitive dysfunction and increased hippocampal BDNF, Ac-H3, and Ac-H4. Exposure to 2.5% sevoflurane for 3 h during late-pregnancy decreased hippocampal BDNF, Ac-H3, and Ac-H4 in the offspring but had no effect on cognitive function. However, when the exposure time was 6 h, impaired spatial learning and memory were linked to reduced BDNF, Ac-H3, and Ac-H4, which could be reversed by EE.

Animals , Female , Pregnancy , Rats , Cognitive Dysfunction , Acetylation , Histones , Maze Learning , Brain-Derived Neurotrophic Factor , Sevoflurane , Hippocampus
Braz. j. med. biol. res ; 52(11): e8899, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039258


Few behavioral tests allow measuring several characteristics and most require training, complex analyses, and/or are time-consuming. We present an apparatus based on rat exploratory behavior. Composed of three different environments, it allows the assessment of more than one behavioral characteristic in a short 3-min session. Factorial analyses have defined three behavioral dimensions, which we named Exploration, Impulsivity, and Self-protection. Behaviors composing the Exploration factor were increased by chlordiazepoxide and apomorphine and decreased by pentylenetetrazole. Behaviors composing the Impulsivity factor were increased by chlordiazepoxide, apomorphine, and both acute and chronic imipramine treatments. Behaviors composing the Self-protection factor were decreased by apomorphine. We submitted Wistar rats to the open-field test, the elevated-plus maze, and to the apparatus we are proposing. Measures related to exploratory behavior in all three tests were correlated. Measures composing the factors Impulsivity and Self-protection did not correlate with any measures from the two standard tests. Also, compared with existing impulsivity tests, the one we proposed did not require previous learning, training, or sophisticated analysis. Exploration measures from our test are as easy to obtain as the ones from other standard tests. Thus, we have proposed an apparatus that measured three different behavioral characteristics, was simple and fast, did not require subjects to be submitted to previous learning or training, was sensitive to drug treatments, and did not require sophisticated data analyses.

Animals , Male , Anxiety/psychology , Behavior, Animal/physiology , Behavioral Research/instrumentation , Exploratory Behavior/physiology , Fear/physiology , Impulsive Behavior/physiology , Time Factors , Anti-Anxiety Agents/pharmacology , Behavior, Animal/drug effects , Apomorphine/pharmacology , Chlordiazepoxide/pharmacology , Rats, Wistar , Maze Learning/drug effects , GABA Antagonists/pharmacology , Dopamine Agonists/pharmacology , Exploratory Behavior/drug effects , Fear/drug effects , Impulsive Behavior/drug effects , Antidepressive Agents, Tricyclic/pharmacology
Braz. j. med. biol. res ; 52(11): e8371, 2019. graf
Article in English | LILACS | ID: biblio-1039257


Oxiracetam (ORC) is a commonly used nootropic drug for improving cognition and memory impairments. The therapeutic effect and underlying mechanism of ORC in vascular dementia (VaD) treatment remain unknown. In this study, 3-month-old male Sprague-Dawley rats with permanent bilateral common carotid artery occlusion-induced VaD were treated orally with low (100 mg/kg) or high (200 mg/kg) dose ORC once a day for 4 weeks. The results of the Morris water maze test and Nissl staining showed that ORC treatment significantly alleviated learning and memory deficits and neuronal damage in rats with VaD. Mechanistically, the protein levels of a panel of genes associated with neuronal apoptosis (Bcl-2, Bax) and autophagy (microtubule-associated protein 1 chain 3, Beclin1, p62) were significantly altered by ORC treatment compared with VaD, suggesting a protective role of ORC against VaD-induced neuronal apoptosis and autophagy. Moreover, the Akt/mTOR pathway, which is known to be the upstream signaling governing apoptosis and autophagy, was found to be activated in ORC-treated rats, suggesting an involvement of Akt/mTOR activation in ORC-rendered protection in VaD rats. Taken together, this study demonstrated that ORC may alleviate learning and memory impairments and neuronal damage in VaD rats by altering the expression of apoptosis/autophagy-related genes and activation of the Akt/mTOR signaling pathway in neurons.

Animals , Male , Rats , Pyrrolidines/administration & dosage , Dementia, Vascular/drug therapy , Signal Transduction/physiology , Neuroprotective Agents/administration & dosage , Proto-Oncogene Proteins c-akt/metabolism , Cognitive Dysfunction/drug therapy , Autophagy/drug effects , Dementia, Vascular/physiopathology , Dementia, Vascular/metabolism , Rats, Sprague-Dawley , Apoptosis/drug effects , Maze Learning/drug effects , Disease Models, Animal , TOR Serine-Threonine Kinases/metabolism , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/metabolism
Acta cir. bras ; 34(12): e201901205, 2019. graf
Article in English | LILACS | ID: biblio-1054687


Abstract Purpose To investigate the effects of huperzine A (HupA) on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia. Methods Thirty-six Sprague Dawley rats (20-22 months old) were randomly divided into control, isofluran, and isoflurane+HupA groups; 12 rats in each group. The isoflurane+HupA group was intraperitoneally injected with 0.2 mg/kg of HupA. After 30 min, isoflurane inhalation anesthesia was performed in the isoflurane and isoflurane+HupA groups. After 24 h from anesthesia, Morris water maze experiment and open-field test were performed. Hippocampal inflammatory and neurotrophic factors were determined. Results Compared with isoflurane group, in isofluran+HupA group the escape latency of rats was significantly decreased (P < 0.05), the original platform quadrant residence time and traversing times were significantly increased (P < 0.05), the central area residence time was significantly increased (P < 0.05), the hippocampal tumor necrosis factor α, interleukin 6 and interleukin 1β levels were significantly decreased (P < 0.05), and the hippocampal nerve growth factor, brain derived neurotrophic factor and neurotrophin-3 levels were significantly increased (P < 0.05). Conclusion HupA may alleviate the cognitive impairment in rats after isoflurane anesthesia by decreasing inflammatory factors and increasing hippocampal neurotrophic factors in hippocampus tissue.

Humans , Animals , Male , Sesquiterpenes/pharmacology , Neuroprotective Agents/pharmacology , Anesthetics, Inhalation/adverse effects , Alkaloids/pharmacology , Hippocampus/drug effects , Nerve Growth Factors/drug effects , Enzyme-Linked Immunosorbent Assay , Random Allocation , Reproducibility of Results , Interleukin-6/analysis , Rats, Sprague-Dawley , Maze Learning , Interleukin-1beta/analysis , Hippocampus/metabolism , Isoflurane/adverse effects , Anesthesia/adverse effects , Nerve Growth Factors/analysis
Article in Chinese | WPRIM | ID: wpr-776546


OBJECTIVE@#To study the effects of prenatal cold stress on the behavior and mood of offspring in pregnant rats.@*METHODS@#Six SPF-class Wister pregnant rats were randomly divided into normal temperature control group and cold stress group with 3 rats in each group. The pregnant female rats in the normal temperature control group were kept in the environment of (22 ±2)℃, and the pregnant female rats in the cold stress group were placed in the artificial intelligence climate chamber at(4 ±0.1)℃ for 7 days before the birth, and the young rats were divided into normal temperature after the young rats were born. After the young rats were born, they were divided into normal temperature control group of male rats (MR, 22), normal temperature control group of mother rats (FR, 15), cold stress group of male rats (MC, 15), and cold stress group of female rats (FC, 15) .In the fourth generation of the offspring, the open field experiment and the elevated cross maze test were carried out.@*RESULTS@#In the open field experiment, there was no significant difference in spontaneous activity and exploration behavior between the normal temperature control group and the cold stress group (P>0.05). In the elevated plus maze experiment, the retention time of the open arms, the number of open arms and the distance of the male and female rats in the cold stress group were significantly higher than those in the normal temperature control group (P<0.05).@*CONCLUSION@#Prenatal maternal cold stress has no significant effect on spontaneous activity, exploration behavior and activity level of offspring, but the offspring have obvious abnormal behaviors with reduced anxiety behavior.

Animals , Anxiety , Behavior, Animal , Cold-Shock Response , Exploratory Behavior , Female , Male , Maze Learning , Pregnancy , Prenatal Exposure Delayed Effects , Random Allocation , Rats , Stress, Psychological
Article in Chinese | WPRIM | ID: wpr-776537


OBJECTIVE@#To investigate the effects of rutaecarpine on high glucose-induced Alzheimer's disease-like pathological and cognitive dysfunction and its mechanism in rats.@*METHODS@#Adult male SD rats were randomly divided into three groups (n=20): control group, high glucose group and rutaecarpine group. Rats in the control group were fed with conventional feed and tap water. The rats in the high glucose group were fed with conventional feed and 20% sucrose water. The rutaecarpine group was fed with fodder contain 0.01% rutaecarpine and 20% sucrose water. Morris water maze test was used to detect learning and memory and cognitive function of three groups rats after 24 weeks of feeding. Western blot analysis was used to detect tau protein at Thr205 and Ser214 sites in each group. Phosphorylation levels of GSK-3β in serine 9 site (S9-GSK-3β) and PP2A at cycline 307 site (Y307-PP2AC) were also detected. Immunohistochemistry further confirmed tau protein at Thr205 site in each group both in hippocampus and cortex.@*RESULTS@#Compared with the control group, Morris water maze results showed that the latency of finding the hidden platform of the rats in high glucose group was increased significantly and the number of crossing platforms and the target quadrant residence time were significantly decreased (all P<0.05). Immunohistochemistry showed that the phosphorylation level of tau protein at Thr205 site was significantly increased in the high glucose group compared with the control group, and the phosphorylation level of tau protein at Thr205 site in the rutaecarpine group was higher than that in the high glucose group. Western blot analysis showed that the phosphorylation level of tau protein in the high glucose group was significantly increased at Thr205 and Ser214 site compared with the control group, but the phosphorylation level of pS9-GSK-3β was significantly decreased (all P <0.05). Compared with the high glucose group, the latency of finding the hidden platform of the rats in rutaecarpine group was significantly decreased, and the number of crossing platforms and the target quadrant residence time were significantly increased (both P<0.05). Compared with the high glucose group, the phosphorylation levels of tau protein at Thr205 and Ser214 sites showed a significant decrease, but the phosphorylation level of pS9-GSK-3β was significantly increased (all P<0.05).@*CONCLUSION@#Rutaecarpine can alleviate AD-like cognitive dysfunction induced by high glucose, possibly by enhancing pS9-GSK-3β phosphorylation, down-regulating GSK-3β activity, and thus reducing hyperphosphorylation of tau-associated sites.

Alzheimer Disease , Drug Therapy , Animals , Cognitive Dysfunction , Drug Therapy , Glucose , Glycogen Synthase Kinase 3 beta , Chemistry , Indole Alkaloids , Pharmacology , Male , Maze Learning , Phosphorylation , Quinazolines , Pharmacology , Random Allocation , Rats , Rats, Sprague-Dawley , tau Proteins , Chemistry
Article in Chinese | WPRIM | ID: wpr-776497


OBJECTIVE@#To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats.@*METHODS@#Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1β), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected.@*RESULTS@#Compared to sham group, the escape latency in VCI group was significantly extended (P<0.01) and the times of passing through the platform were decreased remarkably (P<0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P<0.01), while the contents of MDA, TNF-α, IL-1β and MAO were increased remarkably (P<0.01). Compared with VCI group, the escape latency in berberine-treated groups was shortened significantly (P<0.01, P<0.05) and the times of passing through the platform were increased remarkably (P<0.01, P<0.05), the levels of SOD, GSH and 5-HT were increased significantly (P<0.01), while the contents of TNF-α, IL-1β and MAO were decreased remarkably (P<0.01).@*CONCLUSION@#Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.

Animals , Berberine , Pharmacology , Cognitive Dysfunction , Drug Therapy , Hippocampus , Inflammation , Maze Learning , Memory , Oxidative Stress , Random Allocation , Rats , Rats, Sprague-Dawley , Rats, Wistar
Article in Chinese | WPRIM | ID: wpr-776495


OBJECTIVE@#To investigate the effects of Acorus tatarinowii Schott and its active component 5- hydroxymethyl furfural (HMF) on learning and memory and ERK/CREB signal in hippocampus of rats with exercise-induced fatigue.@*METHODS@#SD rats were randomly divided into normal group (A), exercise group (B), exercise + HMF low, middle and high dose treatment group (C, D, E), exercise + acorus tatarinowii Schott low, middle and high dose treatment group (F, G, H), with ten rats in each group. The rats in group C, D and E were treated with HMF at the doses of 0.10, 1.00 and 3.00 mg. kg by ig. The rats in group F, G and H were treated with the extracts of Acorus tatarinowii Schott at the doses of 0.12, 1.20 and 4.80 g. kg by ig. Learning and memory of rats were tested by the method of water maze experiment, and the expression levels of p-ERK1/2 and p-CREB protein in hippocampus of rats were tested by the method of Western blot in the end of the experiment.@*RESULTS@#The escape latencies of E and H groups were lower than those of groups B, C, D, F and G; and the numbers of plateau crossing were more than those of groups B, C, D, F and G and the expression levels of p-ERK1/2, p-CREB protein were higher than those of groups B, C, D, F and G , respectively(P < 0.01). There was no significant difference in the above indexes among groups A, E and H(P>0.05) except that the expression levels of p-ERK2 protein in group E were lower than those in group A and H (P<0.05).@*CONCLUSION@#Acorus tatarinowii and its active component- HMF can improve the learning and memory of rats with exercise-induced fatigue, and the mechanism is related to the up-regulation of ERK / CREB signal in hippocampus of rats with exercise-induced fatigue.

Acorus , Chemistry , Animals , Cyclic AMP Response Element-Binding Protein , Metabolism , Fatigue , Drug Therapy , Furaldehyde , Pharmacology , Hippocampus , Metabolism , MAP Kinase Signaling System , Maze Learning , Memory , Physical Conditioning, Animal , Phytochemicals , Pharmacology , Random Allocation , Rats , Rats, Sprague-Dawley
Neuroscience Bulletin ; (6): 347-361, 2019.
Article in English | WPRIM | ID: wpr-775441


Occupational exposure to 1-bromopropane (1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors (NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BP-induced cognitive dysfunction. Male Wistar rats were administered with MK801 (0.1 mg/kg) prior to 1-BP intoxication (800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological, and immunological analyses. We found that the spatial learning and memory were significantly impaired in the 1-BP group, and this was associated with neurodegeneration in both the hippocampus (especially CA1 and CA3) and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex. Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.

Animals , Brain , Metabolism , Pathology , Cognitive Dysfunction , Drug Therapy , Metabolism , Pathology , Disease Models, Animal , Dizocilpine Maleate , Pharmacology , Excitatory Amino Acid Antagonists , Pharmacology , Hydrocarbons, Brominated , Inflammasomes , Metabolism , Male , Maze Learning , Physiology , Microglia , Metabolism , Pathology , NLR Family, Pyrin Domain-Containing 3 Protein , Metabolism , Neurons , Metabolism , Pathology , Nootropic Agents , Pharmacology , Random Allocation , Rats, Wistar , Receptors, N-Methyl-D-Aspartate , Metabolism , Spatial Memory , Physiology , Specific Pathogen-Free Organisms
Braz. j. biol ; 78(3): 501-504, Aug. 2018. tab
Article in English | LILACS | ID: biblio-951586


Abstract We evaluated the involvement of the serotonergic system on memory formation and learning processes in healthy adults Wistar rats. Fifty-seven rats of 5 groups had one serotonergic nuclei damaged by an electric current. Electrolytic lesion was carried out using a continuous current of 2mA during two seconds by stereotactic surgery. Animals were submitted to learning and memory tests. Rats presented different responses in the memory tests depending on the serotonergic nucleus involved. Both explicit and implicit memory may be affected after lesion although some groups showed significant difference and others did not. A damage in the serotonergic nucleus was able to cause impairment in the memory of Wistar. The formation of implicit and explicit memory is impaired after injury in some serotonergic nuclei.

Resumo Avaliar a participação do sistema serotoninérgico em processos de formação de memória e aprendizagem em ratos Wistar adultos saudáveis. Cinquenta e sete ratos de 5 grupos tinham um núcleo serotoninérgico danificado por uma corrente elétrica. A lesão eletrolítica foi realizada utilizando uma corrente contínua de 2 mA durante dois segundos por cirurgia estereotáxica. Os animais foram submetidos a testes de aprendizagem e memória. Os ratos apresentaram respostas diferentes nos testes de memória, dependendo do núcleo serotoninérgica envolvido. A memória explícita e implícita pode ser afetada após a lesão, embora alguns grupos apresentaram diferença significativa e outros não. A lesão no núcleo serotoninérgico foi capaz de causar danos na memória de Wistar. A formação da memória implícita e explícita é prejudicada após a lesão em alguns núcleos serotoninérgicos.

Animals , Male , Rats , Maze Learning , Serotonergic Neurons , Hippocampus/physiopathology , Learning , Memory Disorders/physiopathology , Neuronal Plasticity , Behavior, Animal , Rats, Wistar , Disease Models, Animal , Hippocampus/injuries , Memory
Int. j. morphol ; 36(3): 1108-1117, Sept. 2018. tab, graf
Article in English | LILACS | ID: biblio-954238


Unbalanced nutrition during perinatal period causes varying degrees of perturbations in the metabolism and cognitive functions of offspring. The aim of this study was to investigate effects of maternal and postweaning high-fat diet (HFD) exposure on the growth parameters, hippocampal functions and morphology of offspring in a sex-dependent manner. Spraque-Dawley rats were fed either standard (10 % fat) or saturated-fat (65 % fat) diet during their gestation and lactation period. After weaning, pups were sustained in same diet for 6 more weeks. Body mass index (BMI) of pups were monitored weekly, then spontaneous locomotor activities were recorded. Spatial learning and memory functions were analyzed by Morris Water Maze (MWM) test. Total volumetric changes of hippocampal subfields were estimated by Cavalieri method. HFD exposure produced sex-dependent alterations in BMI, serum lipid and activity levels. MWM results showed no significant difference among groups. However, retrieval indexes were higher in HFD-fed males. Total volumetric analysis of the dentate gyrus was comparable, but the pyramidal cell layer volume of HFD-fed males was lower than those of SD-fed males. Despite alterations in some growth and lipid parameters, maternal and perinatal exposure to HFD did not markedly affect cognitive functions and hippocampal morphology of offspring.

La nutrición desequilibrada durante el período perinatal causa diversos grados de perturbaciones en el metabolismo y las funciones cognitivas en neonatos. El objetivo de este estudio fue investigar los efectos de la exposición a una dieta alta en grasas (HFD) materna y posdestete en los parámetros de crecimiento, las funciones del hipocampo y la morfología de neonatos de una manera dependiente del sexo. Ratas SpragueDawley fueron alimentadas con dieta estándar (10 % grasa) o grasa saturada (65 % grasa) durante su período de gestación y lactancia. Después del destete, las crías se mantuvieron en la misma dieta durante 6 semanas. El índice de masa corporal (IMC) de las crías se controló semanalmente, luego se registraron las actividades locomotoras espontáneas. El aprendizaje espacial y las funciones de memoria se analizaron mediante la prueba Morris Water Maze (MWM). Los cambios volumétricos totales de los subcampos del hipocampo se estimaron mediante el método de Cavalieri. La exposición a HFD produjo alteraciones dependientes del sexo en el IMC, los niveles de lípidos séricos y los niveles de actividad. Los resultados de MWM no mostraron diferencias significativas entre los grupos. Sin embargo, los índices de recuperación fueron más altos en machos alimentados con HFD. El análisis volumétrico total del giro dentado fue comparable, pero el volumen de la capa de células piramidales de los machos alimentados con HFD fue menor que el de los machos alimentados con SD. A pesar de las alteraciones en algunos parámetros lipídicos y de crecimiento, la exposición materna y perinatal a HFD no afectó marcadamente las funciones cognitivas y la morfología del hipocampo de la descendencia.

Animals , Male , Female , Pregnancy , Rats , Prenatal Exposure Delayed Effects , Dietary Fats/adverse effects , Hippocampus/physiopathology , Hippocampus/pathology , Organ Size , Rats, Sprague-Dawley , Maze Learning , Prenatal Nutritional Physiological Phenomena , Animals, Newborn
Acta colomb. psicol ; 21(1): 70-94, Jan.-June 2018. tab, graf
Article in English | LILACS | ID: biblio-886320


Abstract In this study we evaluated the long-term spatial memory in humans. A quasiexperimental design was used in which three groups of undergraduate students were trained in a virtual water maze to locate a hidden platform whose location was indicated by a set of cues. A pre-test without platform was performed prior to the training, and a post-test was conducted immediately after this (Group 0h), or after a retention interval of two (Group 48h) or seven days (Group 168h). For the pre-test, there was no evidence of preference for any area of the maze. Throughout the training trials, the time to find the goal decreased without differences between groups. During the post-test, all groups showed a preference for the reinforced quadrant, although the spent time, swimming distance, and accuracy of the search behavior in that area was equivalent between Group 0 h and Group 48 h, but higher than that shown by the Group 168 h. These data indicate changes in long-term spatial memory in humans, occurring after an interval of 48 h after its acquisition. The results are discussed on the basis of general memory processes and specific processes proposed by particular spatial memory theories. The clinical and comparative psychology implications are also addressed.

Resumo Neste estudo, avaliou-se a memória espacial de longo prazo em humanos. Para isso, empregou-se um desenho quase-experimental no qual se treinou três grupos de estudantes de graduação num labirinto virtual de água para localizar uma plataforma oculta cuja posição era sinalizada por um conjunto de chaves. Realizou-se um pré-teste sem plataforma antes do treinamento, e imediatamente depois se conduziu um pós-teste (Grupo 0 h), assim como depois de um intervalo de retenção de dois dias (Grupo 48 h) e de sete dias (Grupo 168 h). No pré-teste, não se encontrou evidência de preferência por alguma área do labirinto. Ao longo dos ensaios de treinamento, o tempo para encontrar a meta diminuiu sem diferenças entre grupos. Durante o pós-teste, todos os grupos mostraram uma preferência pelo quadrante reforçado, contudo o tempo de permanência, a distância de nado e a precisão do comportamento de busca nessa área foi equivalente entre o Grupo 0 h e o Grupo 48 h, embora maior à amostragem pelo Grupo 168 h. Esses dados indicam mudanças ocorridas 48 h depois da aquisição na memória espacial de longo prazo em humanos. Discutem-se os resultados a partir de processos gerais de memória e de processos específicos propostos por teorias particulares de memória espacial; ao final, abordam-se as implicações clínicas e pertinentes ao campo da psicologia comparada.

Resumen En este estudio se evaluó la memoria espacial a largo plazo en humanos. Para ello, se empleó un diseño cuasiexperimental en el que se entrenó a tres grupos de estudiantes de pregrado en un laberinto virtual de agua para localizar una plataforma oculta cuya ubicación era señalada por un conjunto de claves. Se realizó un pretest sin plataforma antes del entrenamiento, e inmediatamente después se condujo un postest (Grupo 0 h), así como después de un intervalo de retención de dos días (Grupo 48 h) y siete días (Grupo 168 h). En el pretest no se encontró evidencia de preferencia por alguna zona del laberinto. A lo largo de los ensayos de entrenamiento, el tiempo para encontrar la meta disminuyó sin diferencias entre grupos. Durante el postest, todos los grupos mostraron una preferencia por el cuadrante reforzado, sin embargo, el tiempo de permanencia, la distancia de nado y la precisión de la conducta de búsqueda en dicha zona fue equivalente entre el Grupo 0 h y el Grupo 48 h, aunque mayor a la mostrada por el Grupo 168 h. Estos datos indican cambios ocurridos 48 h después de la adquisición en la memoria espacial a largo plazo en humanos. Se discuten los resultados a partir de procesos generales de memoria y procesos específicos propuestos por teorías particulares de memoria espacial; y al final se abordan las implicaciones clínicas y pertinentes al campo de la psicología comparada.

Humans , Male , Female , Young Adult , Retention, Psychology , Maze Learning , Spatial Memory
Arq. neuropsiquiatr ; 76(1): 32-40, Jan. 2018. graf
Article in English | LILACS | ID: biblio-888340


ABSTRACT In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.

RESUMO Neste estudo, foi investigado o efeito da timoquinona (TQ) contra deficiências de memória induzidas por propiltiouracilo (PTU) em ratos juvenis. Os ratos foram agrupados em grupos: controle, Hypo, Hypo-TQ5, e Hypo-TQ10. O PTU aumentou o tempo de latência no teste do labirinto aquático de Morris (MWM) e diminuiu o atraso para entrar no compartimento escuro no teste de evasão passiva (PA). Ambas as doses de TQ diminuíram o tempo de latência no teste de MWM e aumentaram o atraso para entrar no compartimento escuro no teste de PA. O PTU também aumentou os metabolitos de malondialdeído (MDA) e óxido nítrico (NO) no cérebro, enquanto reduziu o teor de tiol e as atividades de superóxido dismutasa (SOD) e catalasa (CAT) e o nível sérico de T4. Ambas as doses de TQ diminuíram os metabolitos de MDA e de NO no cérebro, aumentaram o conteúdo de tiol e as atividades de SOD e CAT e o nível de T4 no soro. Os resultados do presente estudo mostraram que a TQ protegeu contra deficiências de memória induzidas por PTU em ratos.

Animals , Male , Benzoquinones/pharmacology , Oxidative Stress/drug effects , Hypothyroidism/complications , Learning Disabilities/drug therapy , Memory Disorders/drug therapy , Antioxidants/pharmacology , Propylthiouracil , Avoidance Learning/drug effects , Superoxide Dismutase/analysis , Antithyroid Agents , Brain Injuries/metabolism , Catalase/analysis , Rats, Wistar , Maze Learning/drug effects , Disease Models, Animal , Hippocampus/drug effects , Hypothyroidism/chemically induced , Learning Disabilities/chemically induced , Malondialdehyde/analysis , Memory Disorders/chemically induced , Nitric Oxide/analysis