8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

We describe the development of quinolylnitrones (QNs) as multifunctional ligands inhibiting cholinesterases (ChEs: acetylcholinesterase and butyrylcholinesterase-hBChE) and monoamine oxidases (hMAO-A/B) for the therapy of neurodegenerative diseases. We identified QN 19, a simple, low molecular weight nitrone, that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde. Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition, yet unexpectedly showed potent inhibition of hBChE (IC50 = 1.06 ± 0.31 nmol/L) and hMAO-B (IC50 = 4.46 ± 0.18 μmol/L). The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding, which was further studied by enzyme kinetics. Compound 19 acted as a free radical scavenger and biometal chelator, crossed the blood-brain barrier, was not cytotoxic, and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease. In addition, in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination. Importantly, chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice, underscoring the disease-modifying effect of QN 19.

Effect of amitriptyline on learning and memory consolidation in the male Wistar rats with an experimental model of pentylenetetrazole-induced seizure

Abstract Amitriptyline (AMT) was developed for the treatment of chronic and neuropathic pain. There is also evidence it may be useful in the treatment of neurodegenerative disorders. In this regard, the effect of on the experimental model of seizures and memory impairment caused by seizures in rats is investigated in the present study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)). The anticonvulsant effect of AMT (10 and 20 mg/kg, i.p.) was evaluated in the seizure model. The effect on memory was assessed using passive avoidance (PA) learning and memory test. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for oxidant/antioxidant assays (malondialdehyde (MDA), and glutathione peroxidase (GPx)). Intraperitoneal injection of AMT decreased the mean number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, AMT caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that AMT was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of the AMT drug in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Effects of Beta; 1-adrenoceptors in the Basolateral Amygdala on Spatial Memory, Passive Avoidance, Long-term Potentiation and Neuronal Arborization in the Hippocampal CA1 Region in Response to Unavoidable Stress

Abstract Norepinephrine in the basolateral amygdala (BLA) plays a pivotal role in mediating the effects of stress on memory functions in the hippocampus, however, the functional contribution of β1-adrenergic receptors on the BLA inputs to the CA1 region of hippocampus and memory function are not well understood. In the present study the role of β1-adrenoreceptor in the BLA on memory, neuronal arborization and long-term potentiation (LTP) in the CA1 region of hippocampus was examined by infusion the β1-adrenoreceptor agonist (Dobutamine; 0.5µl/side) or antagonist (Atenolol; 0.25µL/side) bilaterally into the BLA before foot-shock stress. Passive avoidance test results showed that Step-through latency time was significantly decreased in the stress group rats one, four and seven days after the stress, which intra-BLA injection of Atenolol or Dobutamine before stress couldn't attenuate this reduction. Barnes-maze results revealed that infusion of Dobutamine and Atenolol significantly reduced spatial memory indicators such as increased latency time, the number of errors and the distance traveling to achieve the target hole in the stress group. These learning impairments in stress rats correlated with a reduction of LTP in hippocampal CA1 synapses in-vivo, which infusion of Dobutamine and Atenolol couldn't attenuate the population spike amplitude and mean-field excitatory postsynaptic potentials (fEPSP) slope reduction induced by stress. Also, the Golgi-Cox staining demonstrated that infusion of Atenolol attenuated stress decreased CA1 region dendritic and axonal arborization. These results suggest that β1-adrenergic receptors activation or block seem to exacerbate stress-induced hippocampal memory deficits and this effect is independent of CA1 LTP modulation.

Evaluation of Acute and Chronic Effects of D-Galactose on Memory and Learning in Wistar Rats

OBJECTIVE: D-galactose has been commonly used in rodent models to induce accelerated effects of aging, including those on learning, memory, and muscular tone and coordination. This is normally seen on chronic administration of D-galactose. However, there is minimal suggestive evidence on the short-term effects of the same. The aim of the study was to study the acute and chronic effects of D-galactose on learning and memory in Wistar rats. METHODS: Twenty four male Wistar rats were randomly assigned to the control, standard (rivastigmine), oral D-galactose (200 mg/kg/day) and subcutaneous D-galactose (200 mg/kg/day) for a total duration of 8 weeks. Effects on learning and memory were assessed at 2 weeks, 4 weeks and 8 weeks by Morris water maze model and passive avoidance testing. RESULTS: Both oral and subcutaneous D-galactose showed positive effects on learning and memory on acute dosing, whereas this beneficial effect was lost during chronic dosing. CONCLUSION: Short-term administration of D-galactose showed positive effects, while long-term administration nullified these effects.

Transient forebrain ischemia induces impairment in cognitive performance prior to extensive neuronal cell death in Mongolian gerbil (Meriones unguiculatus)

In Mongolian gerbils, bilateral common carotid artery occlusion (BCCAO) for several minutes induces ischemia, due to an incomplete circle of Willis, resulting in delayed neuronal cell death in the Cornet d'Ammon 1 (CA1) region of the hippocampus. Neuronal cell death in the hippocampus and changes in behavior were examined after BCCAO was performed for 5 min in the gerbils. One day after BCCAO, the pyramidal neurons of the CA1 region of the hippocampus showed degenerative changes (clumped chromatin in nuclei). At 5 and 10 days after BCCAO, extensive neuronal cell death was observed in the hippocampal CA1 region. Cognitive performance was evaluated by using the radial maze and passive avoidance tests. In the radial maze test, which examines win-stay performance, the number of errors was significantly higher in ischemic gerbils than in sham-operated gerbils on days 1 and 2 post-operation. In the passive avoidance test, the latency and freezing times were significantly shorter in ischemic gerbils than in sham-operated gerbils on the days 1, 2, and 4–6 post-operation. These results indicate that transient forebrain ischemia impairs cognitive performance, even immediately after the ischemic insult when there are only subtle signs of neuronal cell death.

Anchusa italica extract: phytochemical and neuroprotective evaluation on global cerebral ischemia and reperfusion

Abstract Stroke is the third leading cause of mortality and disability in industrial countries. Treatment with herbs with antioxidant properties has been reported to be an alternative to the conventional treatments. This study was conducted to investigate the effect of Anchusa italica extract on hippocampal injury induced by transient global cerebral ischemia and reperfusion in the rat. To do so, 50 rats were randomly assigned to five groups; control, sham, ischemia, and 50 or 100 mg/kg of Anchusa italica treated animals. Ischemia was induced by occlusion of carotid artery for 30 minutes. Afterward, behavioral tests and biochemical analyses were conducted. Induction of ischemia/reperfusion caused a decline in learning and passive avoidance memory in rats. Moreover, Anchusa italica caused an increase in learning and improved the passive avoidance memory. Induction of ischemia/reperfusion caused a decrease in the antioxidant capacity of the brain and serum as well as an increase in the malondialdehyde of the brain and serum. Anchusa italica led to an increase in the antioxidant capacity of the brain and serum and decrease in the malondialdehyde of the brain and serum. Overall, because of its protective effects on spatial memory, passive avoidance learning, antioxidant capacity, and lipid peroxidation during ischemia/reperfusion, Anchusa italica might be beneficial in ischemic patients.

The effects of regular exercise on capsaicin-induced pulpal pain and pain-induced changes in passive avoidance learning and memory in rats

BACKGROUND: Pulpal pain is one of the most common and severe orofacial pain conditions with considerable adverse effects on physiological processes including learning and memory. Regular exercise is known to be effective on cognitive function as well as pain processing in the central nervous system. Here, the possible effects of regular exercise on pulpal pain response as well as pain-induced changes in learning and memory efficiency in rats were investigated. METHODS: Twenty-four male Wistar rats were randomly assigned to the control, capsaicin, exercise, and exercise plus capsaicin groups. Rats in exercise groups were forced to run on a treadmill with a moderate exercise protocol for 4 weeks. Capsaicin was used to induce dental pulp pain. Passive avoidance learning and memory performance was assessed by using a shuttle box apparatus. RESULTS: According to the results, regular exercise could decrease the time course of capsaicin-induced pulpal pain (P < 0.001). Moreover, in capsaicin-treated rats, passive avoidance acquisition was impaired as compared to the control (P < 0.05) and exercise (P < 0.001) groups. Additionally, regular exercise before capsaicin injection could attenuate capsaicin-induced memory impairments (P < 0.05). CONCLUSIONS: Taken together, the present data showed that regular exercise has inhibitory effects on capsaicin-induced pulpal pain as well as pain-induced cognitive dysfunction in rats.

HPLC analysis of Phenolic Substances and Anti-Alzheimer's Activity of Korean Quercus Species

This study aimed to establish the quantitative method to analyze the content of peroxynitrite-scavengers belonging to polyphenols in six Korean Quercus species (Quercus mongolica, Q. dentata, Q. acutissima, Q. alienta, Q. serrata, and Q. variabilis) by HPLC. The twelve peroxynitrite-scavengers, flavanols (catechins: (+)-catechin, (−)-epicatechin, and (−)-epigallocatechin), flavonols (kaempferol and quercetin), flavonol glycosides (astragalin, quercitrin, and isoquercitrin), flavonol acylated glycosides (astragalin 6″-gallate and isoquercitrin 6″-gallate), gallic acid and its dimer (ellagic acid) were analyzed by HPLC. Further, anti-Alzheimer's activity was assayed in a passive avoidance testusing mice by measuring the retention latency (sec), the concentration of acetylcholine (ACh), and acetylcholinesterase (AChE) activity. Simultaneous analysis of the extracts of the six Quercus leaves was achieved on a Capcell C18 column (5 µm, 250 mm × 4.6 mm i.d.) with a gradient elution of 0.05% HAc and 0.05% HAc in CH₃CN. In the extract of Q. mongolica leaves, the content of gallic acid (32.53 mg/g), (+)-catechin (28.78 mg/g), (−)-epicatehin (22.03 mg/g), astragalin 6″-gallate (20.94 mg/g), and isoquercitrin 6″-gallate (44.11 mg/g) and peroxynitrite-scavenging activity (IC₅₀, 0.831 µg/ml) were high. This extract delayed the retention latency and inhibited acetylcholinesterase activity in scopolamine-induced memory impairment of mice, suggesting that it has anti-Alzheimer's activity.

Effect of Alcohol Consumption in Pregnancy on Pup Quality, Exploratory Behaviour, Memory Retention in Wistar Rats.

Prenatal exposure to alcohol can affect both prenatal and postnatal neurogenesis in the developing brain and impair brain function in their early life. Aim: Our study was aimed to assess the effect of prenatal alcoholic exposure on memory retention and exploratory behavior in young adult rats. We also studied the effect of maternal alcohol intake on pup quality, mortality rate and post natal weight gain of the pups during their weaning period. Methods: Female rats were divided into control and alcohol fed group. Rats in alcoholic group were orally fed (force feeding) with 30% alcohol at a dose of 5g/kg /day. Treatment was started 14 days before mating, continued throughout their gestation period and weaning period. Control group was administrated with equivalent volume of water. Offspring from each group were divided into male and female group. Birth weight, crown-rump length, litter size were taken from the day of delivery, whereas cognitive function test were done from 75th day of post natal life. Statistics: Data obtained from the tests were analyzed by applying independent T test. Results: Single dose of 5g/kg/day maternal ethanol treatment decreased the memory retention (p=0.003), decreased the weight gain during weaning period (p=0.000), increased the locomotor activities (p=0.05) and increased the mortality rate of pups during weaning period. No significant change was observed in the pup quality between control mother and alcoholic mother. Conclusion: The present study showed that maternal alcohol consumption could affect mortality rate of the pups and their post natal weight gain during weaning period. It also affects their cognitive behaviour and locomotor activities in their later life.

Effects of Cholestasis on Learning and Locomotor Activity in Bile Duct Ligated Rats

Background: Cognitive functions are impaired in patients with liver disease. Bile duct ligation causes cholestasis that impairs liver function. This study investigated the impact of cholestasis progression on the acquisition and retention times in the passive avoidance test and on the locomotor activity of rats. Methods: Cholestasis was induced in male Wistar rats by ligating the main bile duct. Locomotor activity, learning and memory were assessed by the passive avoidance learning test at day 7, day 14, and day 21 post-bile duct ligation. The serum levels of bilirubin, alanine aminotransferase, and alkaline phosphatase were measured. Results: The results showed that acquisition time and locomotor activity were not affected at day 7 and day 14, but they were significantly (P < 0.05) impaired at day 21 post-bile duct ligation compared with the results for the control group. Additionally, memory was significantly impaired on day 7 (P < 0.01), day 14, and day 21 (P < 0.001) compared with the control groups. The levels of total bilirubin, direct bilirubin, indirect bilirubin, alanine aminotransferase, and alkaline phosphatase were significantly higher at day 7, day 14, and day 21 post-bile duct ligation compared with the levels in the sham group. Conclusion: Based on these findings, both liver and memory function were affected in the early stage of cholestasis (7 days after bile duct ligation), while learning and locomotor activity were impaired at 21 days after bile duct ligation following the progression of cholestasis.

Ameliorating effect of new constituents from the hooks of Uncaria rhynchophylla on scopolamine-induced memory impairment / 中国天然药物

AIM@#To study the chemical constituents and their anti-amnesic effect from the hooks of Uncaria rhynchophylla.@*METHODS@#The isolation of compounds was performed by chromatographic techniques and their structures were identified on the basis of spectral analysis. Their ameliorating effects on scopolamine-induced memory impairment in vivo using a Morris water-maze task and passive avoidance task system were evaluated.@*RESULTS@#Activity-guided fractionation of the total extracts resulted in the isolation of four constituents, trans-anethole (1), p-anisaldehyde (2), estragole (3), and 3-oxo-olean-12-en-28-oic acid (4), which were found for the first time from this plant.@*CONCLUSION@#Compound 1 exhibited a better memory enhancing effect than tacrine, a positive agent, at the same dose in the passive avoidance test and a similar property in the water-maze test, and its action may be mediated, in part, by the acetylcholine enhancing cholinergic nervous system.

Effects of proteasome inhibitor MG132 on memory acquisition and retrieval in one-trial passive avoidance in mice / 中华行为医学与脑科学杂志

Objective To investigate the effects of proteasome inhibitor MG132 on memory acquisition and memory retrieval in one-trail passive avoidance for mice.Methods MG132 (25 mg/kg) was administrated at different time points to analyze the time-dependent effects of MG132 on hippocampus proteasome activity.MG132 (25 mg/kg) was administrated 3 hours before-training or 1.5 hours pre-test to investigate the effect on memory acquisition and retrieval.The interaction of low dose (12 mg/kg) of MG132 and novelty interference on memory retrieval to studied.Results Hippocampus proteasome activity was significantly blocked when MG132 (25 mg/kg) was administrated 0.5-1.5 hours before analysis.The inhibition recovered as time passing and backed to normal state 24 hours later.A significant difference was showed between vehicle and pre-training,pre-test group (pre-training vehicle (296.03 ± 3.97) s,pre-training (173.30 ± 47.51) s ; pre-test vehicle (199.23 ± 43.01) s,pre-test (44.10 ± 11.16) s).Proteasome inhibitor did not produce a significant effect on memory retrieval (vehicle (174.19 ± 30.54)s,lower dose (174.19± 30.54)s),then only together with a novelty task the retrieval was significantly altered(vehicle (164.02 ±35.26)s,MG132 +novelty group (84.70 ±23.92)s).Conclusion Proteasome inhibitor MG132 can inhibit memory acquisition and memory retrieval.Thereby the effect on memory retrieval is enhanced by novelty.Thus,a physiological proteasome activity is essential for learning abilities.

Pre-ischemia physical activity improved cognition and modified ascorbate change in medial prefrontal cortex after cerebral ischemia / 中华物理医学与康复杂志

Objective To investigate the effect of pre-ischemia physical activity on cognition and ascorbate content in medial prefrontal cortex (mPFC) after cerebral ischemia.Methods Twenty-four Sprague-Dowley rats were enrolled in this study and randomly divided into the following 4 groups:running-ischemia group,running group,ischemia group and shame operation group.Cerebral ischemia was brought about by permanent 2 vessels occlusion (2-VO) method.Treadmill running was used as physical activity training.Ascorbate in mPFC was monitored with in vivo microdialysis coupled with on-line electrochemical flow cell analysis.Passive avoidance was used to test cognitive function at 24 hours after 2-VO cerebral ischemia.Results Neurochemistry study showed that ascorbate level in mPFC increased within 3 hours after 2-VO ischemia and the increase was attenuated in the running-ischemia group.The baseline level of mPFC ascorbate in the four groups has no significant difference.Behavioral data indicated that 3 weeks pre-ischemia running promoted cognitive function recovery after 2-VO ischemia.Conclusion The pre-ischemia physical activity could increase the ascrobate storage in mPFC and enhance the antioxidant ability of this region.Therefore,it is one of the possible neurochemical mechanism underlying pre-ischemia physical activity for the improvement of cognitive function after cerebral ischemia.Thus pre-ischemia physical activity can be of benefit to cognition rehabilitation after stroke.

Effect of Codonopsis lanceolata with Steamed and Fermented Process on Scopolamine-Induced Memory Impairment in Mice

Codonopsis lanceolata (Campanulaceae) traditionally have been used as a tonic and to treat patients with lung abscesses. Recently, it was proposed that the extract and some compounds isolated from C. lanceolata reversed scopolamine-induced memory and learning deficits. The purpose of this study was to evaluate the improvement of cognitive enhancing effect of C. lanceolata by steam and fermentation process in scopolamine-induced memory impairment mice models by passive avoidance test and Morris water maze test. The extract of C. lanceolata or the extract of steamed and fermented C. lanceolata (SFCE) was orally administered to male mice at the doses of 100 and 300 mg/kg body weight. As a result, mice treated with steamed and fermented C. lanceolata extract (SFCE) (300 mg/kg body weight, p.o.) showed shorter escape latencies than those with C. lanceolata extract or the scopolamine-administered group in Morris water maze test. Also, it exerted longer step-through latency time than scopolamine treated group in passive avoidance test. Furthermore, neuroprotective effect of SFCE on glutamate-induced cytotoxicity was assessed in HT22 cells. Only SFCE-treated cells showed significant protection at 500 microg/ml. Interestingly, steamed C. lanceolata with fermentation contained more phenolic acid including gallic acid and vanillic acid than original C. lanceolata. Collectively, these results suggest that steam and fermentation process of C. lanceolata increased cognitive enhancing activity related to the memory processes and neuroprotective effect than original C. lanceolata.

Resistance exercise improves hippocampus-dependent memory

It has been demonstrated that resistance exercise improves cognitive functions in humans. Thus, an animal model that mimics this phenomenon can be an important tool for studying the underlying neurophysiological mechanisms. Here, we tested if an animal model for resistance exercise was able to improve the performance in a hippocampus-dependent memory task. In addition, we also evaluated the level of insulin-like growth factor 1/insulin growth factor receptor (IGF-1/IGF-1R), which plays pleiotropic roles in the nervous system. Adult male Wistar rats were divided into three groups (N = 10 for each group): control, SHAM, and resistance exercise (RES). The RES group was submitted to 8 weeks of progressive resistance exercise in a vertical ladder apparatus, while the SHAM group was left in the same apparatus without exercising. Analysis of a cross-sectional area of the flexor digitorum longus muscle indicated that this training period was sufficient to cause muscle fiber hypertrophy. In a step-through passive avoidance task (PA), the RES group presented a longer latency than the other groups on the test day. We also observed an increase of 43 and 94% for systemic and hippocampal IGF-1 concentration, respectively, in the RES group compared to the others. A positive correlation was established between PA performance and systemic IGF-1 (r = 0.46, P < 0.05). Taken together, our data indicate that resistance exercise improves the hippocampus-dependent memory task with a concomitant increase of IGF-1 level in the rat model. This model can be further explored to better understand the effects of resistance exercise on brain functions.

Effects of Citicoline Acupuncture Point Injection on Learning and Memory Function of Rats with Traumatic Brain Injury / 中国康复理论与实践

@#Objective To explore the effects of citicoline injection into Zusanli point (ST36) on learning and memory function of rats after traumatic brain injury (TBI). Methods The model was induced with the improved Feeney method. The rats were randomly divided into 5 groups: sham-operation group, control group, acupuncture point saline injection group, intraperitoneal drug injection group and acupuncture point drug injection group with 8 rats in each group. The rats in the acupuncture point drug or saline injection group were treated with acupuncture injection of citicoline or saline daily. The rats in the intraperitoneal drug injection group and control group were treated with intraperitoneal injection of citicoline or saline daily. The treatment continued for 14 d. The learning and memory function was evaluated with the Morris water maze test and passive avoidance test. Results Acupuncture point injection of citicoline can significantly shorten the escape latent period of TBI rats in Morris water tests and extend the latent period of learning and memory of TBI rats (P<0.05). Conclusion Acupuncture point injection is effective on the recovery of learning and memory function of rats after TBI.

Effects of single, brief exposure to an 8 mT electromagnetic field on avoidance learning in male and female mice

The present study investigated the effect of extremely low frequency (8 mT, 50 Hz) electromagnetic fields (ELF-EMF) on avoidance learning in mice and compared the effect of an ELF-EMF in adult male and female mice. Learning was evaluated using a passive avoidance learning procedure in a standard wooden box, in which, despite their instinctive tendencies, mice learn to stay on a small platform to avoidant an electric shock. Before each learning session, the animals were exposed to an 8 mT, 50 Hz ELF created by a round coil. Immediately after 60 min exposure to the ELF-EMF, the mice were subjected to avoidance learning. The animals in the sham-exposed control group were placed in the coil for 60 min but were not exposed to the EMF and were subjected to the same behavioral procedures as the experimental group. The comparison of learned behaviors in the experimental and control groups showed that exposure to an 8 mT, 50 Hz ELF for 60 min significantly affected passive avoidance learning in both male (p < .023) and female (p < .015) mice.

Enhancement of basolateral amygdaloid neuronal dendritic arborization following Bacopa monniera extract treatment in adult rats

OBJECTIVE: In the ancient Indian system of medicine, Ayurveda, Bacopa monniera is classified as Medhya rasayana, which includes medicinal plants that rejuvenate intellect and memory. Here, we investigated the effect of a standardized extract of Bacopa monniera on the dendritic morphology of neurons in the basolateral amygdala, a region that is concerned with learning and memory. METHODS: The present study was conducted on 2¹/2-month-old Wistar rats. The rats were divided into 2-, 4- and 6-week treatment groups. Rats in each of these groups were further divided into 20 mg/kg, 40 mg/kg and 80 mg/kg dose groups (n = 8 for each dose). After the treatment period, treated rats and age-matched control rats were subjected to spatial learning (T-maze) and passive avoidance tests. Subsequently, these rats were killed by decapitation, the brains were removed, and the amygdaloid neurons were impregnated with silver nitrate (Golgi staining). Basolateral amygdaloid neurons were traced using camera lucida, and dendritic branching points (a measure of dendritic arborization) and dendritic intersections (a measure of dendritic length) were quantified. These data were compared with the data from the age-matched control rats. RESULTS: The results showed an improvement in spatial learning performance and enhanced memory retention in rats treated with Bacopa monniera extract. Furthermore, a significant increase in dendritic length and the number of dendritic branching points was observed along the length of the dendrites of the basolateral amygdaloid neurons of rats treated with 40 mg/kg and 80 mg/kg of Bacopa monniera (BM) for longer periods of time (i.e., 4 and 6 weeks). CONCLUSION: We conclude that constituents present in Bacopa monniera extract have neuronal dendritic growth-stimulating properties.

Effects of Streptozotocin-Induced Type 1 Diabetes on Cell Proliferation and Neuronal Differentiation in the Dentate Gyrus; Correlation with Memory Impairment / 대한해부학회지

We examined the effects of steptozotocin (STZ)-induced type 1 diabetes on cell proliferation and neuroblasts in the subgranular zone of the hippocampal dentate gyrus (SZDG) of male Wistar rats. Change in memory function was also investigated using the passive avoidance test. In the SZDG, Ki67 (a marker for cell proliferation) positive nuclei were significantly decreased at 2 and 3 weeks and slightly decreased at 4 weeks after STZ treatment. Doublecortin (DCX, a marker for neuronal differentiation)-immunoreactive (+) neuroblasts with tertiary dendrites were significantly decreased in the STZ-treated group compared to those in the vehicle-treated group. However, DCX+ neuroblasts without tertiary dendrites were abundant at 4 weeks after STZ treatment. In addition, retention latency time in STZ-treated group was similar to that of vehicle-treated group at 2 and 3 weeks after STZ treatment. However, the retention latency time was significantly decreased at 4 weeks after STZ treatment. These results suggest that STZ significantly reduced cell proliferation and neuroblasts at 2~3 weeks after STZ treatment, but not at 4 weeks after STZ treatment although memory impairment was detected at 4 weeks after STZ treatment. The gradual reduction of DCX+ neuroblasts with tertiary dendrites may be associated with the impairment of hippocampus-related memory function.

Ascorbic acid protects against restraint stress-induced memory deficits in wistar rats

OBJECTIVE: Chronic stress has been shown to cause oxidative damage in the central nervous system. Although stress-induced impairments in learning and memory have been studied extensively, very few studies have investigated possible ways to prevent their ill effects. The present work was designed to study the protective effects of ascorbic acid in memory loss induced by chronic restraint stress. METHODS: Adult male Wistar rats were designated into the following groups: (i) Normal control, (ii) Ascorbic acid treatment, (iii) Vehicle control, (iv) Restraint stress, (v) Restraint stress + vehicle, and (vi) Restraint stress + ascorbic acid treatment. At the end of 21 days, animals of all groups were subjected to memory tests using Morris water maze and passive avoidance apparatus. Then, the results obtained were compared between the experimental groups. RESULTS: Rats exposed to restraint stress alone and those pretreated with vehicle solution before restrained stress showed deficits in learning and impaired memory retention in the memory tests when compared to animals in other experimental groups. Animals pretreated with ascorbic acid before restraining showed significant improvement in memory retention in the same memory tests. CONCLUSIONS: Results of this study suggest the possibility of using ascorbic acid as a dietary supplement to prevent stress-induced memory impairments.