Adherence to Epilepsy's Medical Recommendations.

The primary problem in the treatment of epilepsy is poor seizure control. Several studies have shown that non-adherence to doctors' recommendations regarding drug dosage, time of drug administration as well as lifestyle modifications are the most frequent causes of the persistence or reoccurrence of seizures, other than cases of misdiagnosis and poor drug selection. The aim of this study was to assess the prevalence of non-compliance with medical recommendations, both in relation to medicine dosage, regularity of administration and lifestyle, and also to determine the factors affecting patients with diagnosed epilepsy. This study was carried out on a total of 169 patients diagnosed with epilepsy who were under the care of an outpatient neurology clinic. The assessment of compliance was performed using the Patient Rating of Compliance Scale (PRCS), Clinician Rating Scale (CRS) and authors' scale. Depending on the scale used, varying degrees of non-compliance were noted. They were as follows-65.3% on the authors' scale, 10% on the PRCS and 9% on the CRS. The following factors influenced compliance with doctors' recommendations: type of epilepsy, consumption of alcoholic beverages, frequency of follow-up visits to the neurology clinic, type of pharmacotherapy and number of medicines taken.

Impact of treatment on blood-brain barrier impairment in Wilson's disease.

INTRODUCTION: Our study assessed changes in concentrations of serum markers for brain damage and blood-brain barrier (BBB) dysfunction in untreated and treated Wilson's disease (WD) patients, and examined correlations between these changes and neurological impairment. OBJECTIVE: These results hold the potential to determine BBB impairment and neurological advancement in WD to develop the most effective treatment for patients with severe neurological deterioration. MATERIAL AND METHODS: The study groups included 171 patients with WD (77 with hepatic and 94 with neurological manifestations), treated either for up to 5 or 15 years, and 88 healthy controls. Serum concentrations of intercellular adhesion molecule 1 (ICAM1), P-selectin, matrix metallopeptidase 9 (MMP9), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein B (S100B) were measured before and during anti-copper treatment. The Unified Wilson's disease Rating Scale (UWDRS) was used to assess neurological advancement. RESULTS: ICAM1 concentrations were elevated before and during anti-copper treatment compared to controls (p < 0.01), but therapy led to substantial decreases both in patients with hepatic (p < 0.01) and in patients with neurological manifestations (p < < 0.05). P-selectin concentrations remained elevated before and during treatment (p < 0.05) regardless of the treatment duration and disease form. MMP9 concentrations before treatment were lower (p < 0.05), but reached control levels during treatment. GFAP concentrations were significantly elevated only in untreated patients with neurological symptoms in the longer-treated group compared to controls (p < 0.05). A significant reduction during treatment was observed only in the shorter-treated neurological group (p < 0.05). No substantial changes were observed in S100B. Only ICAM1 concentrations positively correlated (r = 0.27, p < 0.001) with the UWDRS. CONCLUSIONS: Our results provide evidence of endothelial activation in WD. However, inconclusive GFAP results, and no increase in S100B, do not allow us to conclude whether the reactive gliosis is not prominent or alternatively whether the BBB is disrupted. Elevated ICAM1 concentrations and their correlation with neurological advancement indicate BBB impairment. A decrease in ICAM1 during treatment suggests that the inflammatory process is reduced, and the BBB partially repaired. Decreased MMP9 concentrations may be the result of active liver fibrosis and higher copper concentrations. Elevated P-selectin concentrations indicate a systemic inflammatory process.

Central nervous system disorders after use of dolutegravir: evidence from preclinical and clinical studies.

The evaluation of dolutegravir based on available preclinical and clinical studies reveals a risk of central nervous system (CNS) disorders associated with long-term use of the drug. The available literature on the pharmacokinetics of the drug, including its penetration of the blood-brain barrier, was reviewed, as well as clinical trials assessing the incidence of adverse effects in the CNS and the frequency of its discontinuation. This paper also summarizes the impact of factors affecting the occurrence of CNS disorders and indicates the key role of pharmacovigilance in the process of supplementing knowledge on the safety of drugs, especially those that are newly registered.

Olfactory dysfunction in patients with Wilson's Disease.

INTRODUCTION: Many neurodegenerative disorders are associated with olfactory dysfunction (OD), but little is known about OD in Wilson's Disease (WD). We evaluated olfactory function in patients with WD. MATERIAL AND METHODS: OD was examined in 68 patients with WD and 70 sex- and age-matched healthy controls using subjective testing with 'Sniffin Sticks'. Threshold discrimination identification (TDI) score and its three components (odour detection threshold, discrimination, and identification) were assessed. RESULTS: Compared to controls, patients with WD had a significantly weaker sense of smell in terms of TDI (p < 0.01), odour discrimination (p < 0.01), and identification (p < 0.01), but not in terms of odour detection threshold (p = 0.27). Patients with predominantly neurological symptoms were characterised by greater OD by TDI (p < 0.01), odour detection threshold (p = 0.01), and discrimination (p = 0.03). The presence of pathological lesions (p = 0.04) in brain magnetic resonance imaging and generalised brain atrophy (p = 0.02) predisposed to worse TDI. In the WD group, weak inverse correlations between age and TDI score (r = -0.27), odour detection threshold (r = -0.3), and discrimination (r = -0.3) were found. Male gender was a risk factor for abnormal TDI in both WD and controls (both p = 0.02). CONCLUSIONS: Patients with WD, particularly older individuals, more frequently had OD than healthy volunteers. Predominantly neurological symptoms, and the presence of typical brain MRI changes, predisposed patients with WD to smell disorders.

Protocatechuic Acid Prevents Some of the Memory-Related Behavioural and Neurotransmitter Changes in a Pyrithiamine-Induced Thiamine Deficiency Model of Wernicke-Korsakoff Syndrome in Rats.

The purpose of this research was to investigate the effects of protocatechuic acid (PCA) at doses of 50 and 100 mg/kg on the development of unfavourable changes in cognitive processes in a pyrithiamine-induced thiamine deficiency (PTD) model of the Wernicke-Korsakoff syndrome (WKS) in rats. The effects of PCA were assessed at the behavioural and biochemical levels. Behavioural analysis was conducted using the Foot Fault test (FF), Bar test, Open Field test, Novel Object Recognition test (NOR), Hole-Board test and Morris Water Maze test (MWM). Biochemical analysis consisting of determination of concentration and turnover of neurotransmitters in selected structures of the rat CNS was carried out using high-performance liquid chromatography. PTD caused catalepsy (Bar test) and significantly impaired motor functions, leading to increased ladder crossing time and multiplied errors due to foot misplacement (FF). Rats with experimentally induced WKS showed impaired consolidation and recall of spatial reference memory in the MWM test, while episodic memory related to object recognition in the NOR was unimpaired. Compared to the control group, rats with WKS showed reduced serotonin levels in the prefrontal cortex and changes in dopamine and/or norepinephrine metabolites in the prefrontal cortex, medulla oblongata and spinal cord. PTD was also found to affect alanine, serine, glutamate, and threonine levels in certain areas of the rat brain. PCA alleviated PTD-induced cataleptic symptoms in rats, also improving their performance in the Foot Fault test. In the MWM, PCA at 50 and 100 mg/kg b.w. improved memory consolidation and the ability to retrieve acquired information in rats, thereby preventing unfavourable changes caused by PTD. PCA at both tested doses was also shown to have a beneficial effect on normalising PTD-disrupted alanine and glutamate concentrations in the medulla oblongata. These findings demonstrate that certain cognitive deficits in spatial memory and abnormalities in neurotransmitter levels persist in rats that have experienced an acute episode of PTD, despite restoration of thiamine supply and long-term recovery. PCA supplementation largely had a preventive effect on the development of these deficits, to some extent also normalising neurotransmitter concentrations in the brain.

Long-term Administration of 3-Di-O-Tolylguanidine Modulates Spatial Learning and Memory in Rats and Causes Transition in the Concentration of Neurotransmitters in the Hippocampus, Prefrontal Cortex and Striatum.

The sigma-1 and sigma-2 (σ1 and σ2) receptors are found in high concentrations in the brain, and their altered expression leads to a variety of neuropsychiatric disorders. 3-di-tolylguanidine (DTG) stimulates the activity of both of these receptors. We assessed the effects of administering DTG to adult male Sprague Dawley rats on learning and memory consolidation processes and on the levels of neurotransmitters in selected brain structures. Spatial learning and memory were evaluated in the water maze test. The DTG was administered orally at daily doses of 3 mg/kg (DTG3), 10 mg/kg (DTG10) or 30 mg/kg (DTG30) for 10 weeks before and during the water-maze test. After completion of the experiment, the concentration of monoamines and their metabolites as well as amino acids in structures involved in cognitive performance - the hippocampus, prefrontal cortex, and striatum - were determined using high performance liquid chromatography (HPLC). The DTG10 group showed an improvement in memory processes related to the "new" platform location, whereas the DTG30 group was worse at finding the "old" platform location. Since the administration of DTG led to differences in dopaminergic transmission, it was assumed to influence memory processes in this way. Changes in histidine, serine, alanine, taurine, and glutamic acid levels in selected structures of the brains of rats with memory impairment were also observed. We conclude that long-term administration of DTG modulates spatial learning and memory in rats and changes the concentrations of neurotransmitters in the hippocampus, prefrontal cortex, and striatum..

Seven decades of clinical experience with Wilson's disease: Report from the national reference centre in Poland.

BACKGROUND AND PURPOSE: Wilson's disease (WD) is a rare autosomal recessive disorder causing excessive copper deposition and a spectrum of manifestations, particularly neurological and hepatic symptoms. We analysed the clinical characteristics of patients with WD admitted to the country's only reference centre, which provided long-term care to most adult patients in Poland over seven decades (pre-1959 to 2019). METHODS: Electronic prospective data collection began in the 2000s and, for prior years, medical records were analysed retrospectively. Demographic and clinical characteristics, treatment and outcomes were analysed by decade of diagnosis. Life-years lost were estimated in patients with WD compared with the general population. Kaplan-Meier curves were used for a time-to-death analysis using 2000-2009 as a reference. RESULTS: In total, 929 patients were analysed. The number of patients increased from 21 before 1959 to 315 for 2000 to 2009 period. Mostly males were diagnosed before the 1990s, but the numbers of female patients diagnosed increased thereafter. Initially, most patients presented with neurological manifestations; however, the incidence of hepatic manifestations and asymptomatic presentations increased over time as patients were diagnosed early and consequently were more independent at diagnosis. Fewer Kayser-Fleischer rings were detected recently. Prior to 1970, patients were treated with D-penicillamine (DP); however, since the introduction of zinc, both therapies have been used as often. Since the 1990s, switches between DP and zinc were recorded in 6%-7% of patients. Consistent improvement in survival has been observed over the years. CONCLUSIONS: This is the largest cohort of patients with WD reported in Poland, with the longest follow-up. Earlier diagnosis and prognosis have improved over seven decades.

Autoantibodies in Wilson disease: Impact on clinical course.

Symptoms of Wilson disease (WD) vary and additional factors such as autoimmunity may play an important role in WD pathogenesis. The presence of antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies, neuronal surface antibodies, and onconeural antibodies in WD was investigated using standardized indirect immunofluorescence assays and Western Blot analysis. The presence of all studied autoantibodies was higher in WD patients in comparison to healthy subjects, but there was no statistically significant difference in autoantibodies frequency according to disease manifestation. D-penicillamine treatment was associated with a higher presence of ANA than zinc sulfate but without an increase in autoimmune diseases rate.

Infection with intestinal helminth (Hymenolepis diminuta) impacts exploratory behavior and cognitive processes in rats by changing the central level of neurotransmitters.

Parasites may significantly affect the functioning of the host organism including immune response and gut-brain-axis ultimately leading to alteration of the host behavior. The impact of intestinal worms on the host central nervous system (CNS) remains unexplored. The aim of this study was to evaluate the effect of intestinal infection by the tapeworm Hymenolepis diminuta on behavior and functions of the CNS in rats. The 3 months old animals were infected, and the effects on anxiety, exploration, sensorimotor skills and learning processes were assessed at 18 months in Open Field (OF), Novel Object Recognition (NOR) and the Water Maze (WM) tests. After completing the behavioral studies, both infected and non-infected rats were sacrificed, and the collected tissues were subjected to biochemical analysis. The levels of neurotransmitters, their metabolites and amino acids in selected structures of the CNS were determined by HPLC. In addition, the gene expression profile of the pro- and anti-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-10) was evaluated by Real-Time PCR to determine the immune response within the CNS to the tapeworm infection. The parasites caused significant changes in exploratory behavior, most notably, a reduction of velocity and total distance moved in the OF test; the infected rats exhibited decreased frequency in the central zone, which may indicate a higher level of anxiety. Additionally, parasite infestation improved spatial memory, assessed in the WM test, and recognition of new objects. These changes are related to the identified reduction in noradrenaline level in the CNS structures and less pronounced changes in striatal serotonergic neurotransmission. H. diminuta infestation was also found to cause a significant reduction of hippocampal expression of IL-6. Our results provide new data for further research on brain function during parasitic infections especially in relation to helminths and diseases in which noradrenergic system may play an important role.

Effect of protocatechuic acid on cognitive processes and central nervous system neuromodulators in the hippocampus, prefrontal cortex, and striatum of healthy rats.

OBJECTIVE: : This study aimed to investigate the influence of protocatechuic acid (PCA) on learning, memory, and central nervous system (CNS) neuromodulators in healthy rats, to analyse whether the procognitive effects of PCA found in animal models of memory impairment and described in the literature occur in healthy individuals. METHODS: : PCA was administered p.o. for 48 days at doses of 50 or 100 mg/kg body weight. The cognitive performance was analysed in behavioural tests (open field, novel object recognition, water maze). Then the animals were sacrificed and their hippocampi, prefrontal cortices and striata removed to measure the level of serotonin, dopamine (DA), noradrenaline, their metabolites and amino acids (taurine, histidine, serine, glutamic acid, aspartic acid, γ-aminobutyric acid, alanine) using high-performance liquid chromatography. RESULTS: : No obvious behavioural changes were observed. Post-mortem quantification of monoamines showed that the turnover of DA in the striatum was significantly increased by PCA. Moreover, hippocampal, and cortical levels of histidine were influenced by PCA and significantly decreased. CONCLUSION: : Despite many beneficial effects of PCA in experimentally developed cognitive impairments, it has no sharp effect on memory performance in healthy rats. The influence on the turnover of striatal DA and modulation of the amino acid system by affecting the concentration of histidine deserves a deeper examination due to the role of histamine in neuropsychiatric disorders as well as the functional interactions between histidine and DA metabolism in the brain.

Early exposure to paracetamol reduces level of testicular testosterone and changes gonadal expression of genes relevant for steroidogenesis in rats offspring.

In this study, we investigated the effects of early paracetamol treatment on the testicular level of testosterone and expression of genes important for steroid biosynthesis and reproduction in male rats offspring. Rats were continuously exposed to paracetamol at doses of 5 or 15 mg/kg b.w. during pregnancy and the first two months of the postpartum development. Testosterone level was determined by ELISA. Profile of gene expression for the testicular steroidogenic factors were evaluated using the Real-Time PCR. Our results showed that paracetamol reduces testicular testosterone level and causes compensatory transactivation of genes important for steroidogenesis and reproductive capacity. We have observed significant over-expression of several genes involved in cholesterol transport and steroid biosynthesis e.g., genes for steroidogenic acute regulatory protein, hydroxysteroid dehydrogenases, luteinizing hormone subunit beta, gonadotropin and androgen receptors. Up-regulation of these genes with parallel testosterone reduction in the testicles could be the possible mechanism that maintains and prevents the loss of the steroidogenic function.

Dihydroergotamine affects spatial behavior and neurotransmission in the central nervous system of Wistar rats.

INTRODUCTION: Dihydroergotamine (DHE) is a derivative of an ergot alkaloid used as an antimigraine medication. Nowadays, ergot alkaloids may still endanger the safety of humans and animals as food or medicine pollutants, but the outcomes of long-term DHE administration on the behaviour and neurotransmission remain undescribed. MATERIAL AND METHODS: Adult male Wistar Albino Glaxo rats pre-treated orally with DHE for six weeks were investigated to assess the relationship between concentration of neurotransmitters and behavioural response. The behavioural effects of the drug administered at doses of either 30 µg/kg b.w. (group DHE30, n = 11) or 100 µg/kg b.w. per day (group DHE100, n = 10) were evaluated in the Morris Water Maze. It is known that monoaminergic neurotransmitters (serotonin, noradrenaline and dopamine) in some brain structures (prefrontal cortex, hippocampus, striatum, cerebellum, spinal cord) play a role in the control of cognitive and motor functions. The concentration of neurotransmitters was determined by High Performance Liquid Chromatography (HPLC). RESULTS: Administration of DHE influenced neither the learning processes nor memory in rats. Nevertheless, an increased motor activity of the DHE-administered animals was observed in both the cued and non-cued behavioural tasks. In HPLC examination, changes in the concentration of monoaminergic neurotransmitters and their metabolites were noted in all tested structures, except for the hippocampus. CONCLUSIONS: DHE is able to modulate noradrenergic, serotonergic and dopaminergic neurotransmission that may support the increase in locomotion.

Sigma receptors and neurological disorders.

ABSTARCT: Sigma receptors were identified relatively recently, and their presence has been confirmed in the central nervous system and peripheral organs. Changes in sigma receptor function or expression may be involved in neurological diseases, and thus sigma receptors represent a potential target for treating central nervous system disorders. Many substances that are ligands for sigma receptors are widely used in therapies for neurological disorders. In the present review, we discuss the roles of sigma receptors, especially in the central nervous system disorders, and related therapies.

Aspalathus linearis infusion affects hole-board test behaviour and amino acid concentration in the brain.

Rooibos tea, brewed using Aspalathus linearis leaves, is a popular South African herbal infusion, but its everyday intake is not fully described in terms of the neuropsychopharmacological outcomes. The cell-protective activity of A. linearis is connected with the ability of reducing glycaemia, inflammation as well as oxidative stress. It was already shown that "fermented" rooibos herbal tea (FRHT), which is rich in phenolic compounds, improves the cognitive performance of rats in the water maze and impacts dopaminergic striatal transmission. The present research was taken to extend the knowledge about the feasible behavioural and neurochemical implications of sustained oral FRHT consumption. We hypothesized that it might affect brain amino acid content and thus induce behaviour and neuroprotection. FRHTs of different leaf to water ratios (1:100, 2:100 and 4:100), analysed by chromatographic methods as regards their flavonoid characteristics, were given to rats as only liquid for 3 months. Their behaviour was evaluated in the hole-board test (HBT). Brain amino acids concentration was analysed in the striatum, hippocampus and prefrontal cortex by HPLC-ECD. The rats drinking rooibos tea presented increased motor activity defined as time spent on moving in the HBT. Their exploration measured by head-dipping and rearing was enhanced. Longer time of the testing-box central zone occupation indicated to reduction in anxiety-related behaviour. Excitatory amino acids (aspartate and glutamate) content was decreased in the striatum of animals drinking the infusions whereas taurine level was increased both in the striatum and hippocampus. In conclusion we suggest that long-term FRHT intake affects exploration and anxiety-related behaviour of the rats as well as exerts biochemical outcomes in the brain that support the neuroprotective impact of rooibos tea.

Are antimigraine drugs that influence CGRP levels justified?

Migraine is one of the most common disorders found in everyday clinical practice. Although migraines are not directly life-threatening or permanently disabling, the severity of the pain and symptoms that characterize a migraine attack often prevent normal work and cause difficulties in everyday life. Migraines also affect the patient's family, who often experience stress and depression in response to the patient's condition. Available therapy, used in both acute and chronic treatments, might not provide sufficient improvement. Due to problems like therapy inefficacy, side effects, and intolerance, patients often stop treatments. Recent studies have indicated that drugs that act through calcitonin gene-related peptide (CGRP) can significantly improve migraine therapy. Here, we review results from currently available clinical trials on CGRP receptor antagonists and anti-CGRP monoclonal antibodies.

Hypothalamus - Response to early paracetamol exposure in male rats offspring.

One of the reasons for using paracetamol during pregnancy is fever. The brain structure responsible for maintaining proper body temperature, but also for controlling some endocrine aspects is hypothalamus. In this study we examined the effect of early pretreatment of paracetamol on hypothalamic neurotransmission in rats' offspring. We used two-month old rats previously exposed to paracetamol at doses of 5 (P5) and 15 mg/kg (P15) during gestational development and next postnatally. The concentration of monoamines, their metabolites and amino acids in hypothalamus was chromatographically determined. The results of biochemical analysis were compared with the Control animals (Con). We found differences between groups in the concentration of main noradrenaline metabolite in hypothalamus. The control group had significantly higher level of 3-methoxy-4-hydroxyphenylglycol (MHPG) compared with rats exposed to paracetamol (F(2,27) = 7.96, p < 0.005). Simultaneously the level of dopamine (DA) (F(2,27) = 4.33, p < 0.05) and its metabolite - homovanillic acid (HVA) (F(2,27) = 17.03, p < 0.005) was increased in the hypothalamus of animals treated with lower dose of the drug. Biochemical analyses show an increase in 3,4-dihydroxyphenyl acetic acid (DOPAC) concentration in P5 group compared to the control rats and group treated with higher dose of paracetamol (F(2,27) = 7.37, p < 0.005). In the hypothalamus significant decrease of glutamic acid concentration was also observed in the group treated with paracetamol at dose of 5 mg. These results demonstrated that paracetamol had a significant effect on dopaminergic and noradrenergic neurotransmission and changed the concentration of glutamic acid in hypothalamus - heat-regulating center and important element of hypothalamic-pituitary- gonadal axis.

Administration of protocatechuic acid affects memory and restores hippocampal and cortical serotonin turnover in rat model of oral D-galactose-induced memory impairment.

Protocatechuic acid (PCA) is a phenolic compound believed to have neuroprotective and procognitive activity. d-Galactose (D-Gal) is a sugar, which administered to mammals can induce cognitive deficits. The first aim of this study was to confirm the effectiveness of D-Gal administered orally in inducing cognitive impairment in rats and describe how it affects the concentration of neurotransmitters in rats' brain. The second aim was to evaluate the influence of PCA on learning, memory and neurotransmission in D-Gal-exposed rats. Memory impairment was induced by long-term administration of D-Gal (100 mg/kg body weight/day) directly via oral gavage. PCA (50 or 100 mg/kg body weight/day, respectively) was administered in drinking water. Morris Water Maze test (MWM) to assess learning and spatial memory was initiated after 38 days of treatment and lasted for 10 days. The concentrations of monoamines and their metabolites were evaluated in selected brain regions using high performance liquid chromatography. D-Gal significantly impaired cognitive performance during the acquisition and recall of MWM compared to control rats and changed concentrations of cortical serotonin as well as its cortical and hippocampal turnover. The turnover of dopamine was also influenced by D-Gal. Simultaneously, PCA was found to improve retrieval of acquired information in MWM and to restore brain serotonergic and dopaminergic turnover dysregulated by D-Gal. These findings confirm the usefulness of oral D-Gal in eliciting rat model of mild memory impairment and show that long-term administration of PCA can be beneficial in reversing detrimental changes related to cognitive deficiencies.

Long-term administration of Aspalathus linearis infusion affects spatial memory of adult Sprague-Dawley male rats as well as increases their striatal dopamine content.

ETHNOPHARMACOLOGICAL RELEVANCE: Everyday use of the herbal tea rooibos, produced from Aspalathus linearis (Brum.f) Dahlg. (Fabaceae) is customary in South Africa, a continuation of its historical use by indigenous people. Although evidence of its traditional indications is anecdotal, rooibos tea is regarded as a general health tea. AIMS OF THE STUDY: Available contemporary research indicates to broad cell protective activity of rooibos focusing on its antioxidative, anti-inflammatory, anti-hyperglycaemic and antithrombotic features affecting metabolic syndrome, cardiovascular risk and neuroprotection. Nevertheless little is known about its impact on brain functions. The present experiment aimed to evaluate the possible behavioural and neurochemical effects of long-term oral administration of "fermented"" rooibos herbal tea (FRHT) infusions to adult male Sprague-Dawley rats. MATERIALS AND METHODS: Infusions, prepared using 1, 2 and 4 g of "fermented"" (oxidised) A. linearis leaves for 100 ml of hot water, were characterised in terms of flavonoid content by ultra-high and high performance liquid chromatography (UHPLC-qTOF-MS, HPLC-DAD) and administered to rats as sole drinking fluid for 12 weeks. Spatial memory behaviour was assessed in a modified version of the Morris water maze. Dopamine, noradrenaline, serotonin and their metabolite levels (DOPAC, 3-MT, HVA, MHPG, 5-HIAA) were quantified in prefrontal cortex, hippocampus and striatum by HPLC-ECD. Body weight and blood glucose level were additionally estimated. RESULTS: All FRHT-treated rats showed improvement of long-term spatial memory defined as increased number of crossings over the previous platform position in SE quadrant of the water maze. It was not accompanied by excessive motor activity. Striatal dopamine and its metabolite 3-MT (3-methoxytyramine) levels were increased in treated rats. There were no differences in body weight gain between control and treated animals but blood glucose level was significantly lower in the latter ones. CONCLUSION: The improvement of long-term memory in FRHT-treated rats and stimulating impact of FRHT on their dopaminergic striatal transmission support the wellness enhancing effect of rooibos tea, contributing to a better understanding of the neurological background of traditional habitual consumption of this herbal tea.

Early paracetamol exposure decreases brain-derived neurotrophic factor (BDNF) in striatum and affects social behaviour and exploration in rats.

The biochemical and behavioral responses to prenatal and early postnatal exposure to paracetamol in rats are not well understood. The effect of daily maternal and early life administration of 5 mg/kg (group P5) or 15 mg/kg paracetamol (group P15) was evaluated in two-month old male rats, relative to control animals receiving tap water (Con). Social behavior and episodic memory were investigated with Social Interaction and Novel Object Recognition (NOR) tests. Quantification of brain-derived neurotrophic factor (BDNF) was determined in prefrontal cortex, hippocampus and striatum using enzyme-linked immunosorbent assay (ELISA). Control animals exhibited a higher total frequency of social interactions and greater frequency of sniffing compared to rats exposed to paracetamol, and we found a statistically significant increase in the occurrence of pinning in paracetamol-treated animals. Rats from the 15 mg/kg group exhibited a greater interest in objects in the NOR test and spent more time exploring objects during the familiarization and choice phases. Biochemical analysis showed significant differences in striatal BDNF between the groups, specifically, a nearly two-fold decrease in striatal BDNF in the paracetamol groups (P5: 6.78 ±â€¯0.60 pg/mg; P15: 6.06 ±â€¯0.46 pg/mg) relative to the control group (Con: 11.33 ±â€¯2.00 pg/mg). These results indicate that paracetamol exposure induces changes in social behaviour and exploration in rats and results in a significant decrease of striatal BDNF.

Long-term administration of Greek Royal Jelly decreases GABA concentration in the striatum and hypothalamus of naturally aged Wistar male rats.

Royal Jelly (RJ) is a unique substance obtained from bees that has been used widely in European and Asian traditional medicine for its potential to prevent signs of aging through its antioxidative, anti-inflammatory, anti-hyperglycemic and anti-hypercholesterolemic properties. We recently reported an enhancement in spatial memory along with changes in monoaminergic transmission in aged rats after chronic RJ administration. Here, we aim to further explore the action of RJ on central nervous system activity by examining levels of amino acids in selected brain structures of aged male Wistar rats following 2-months of Greek RJ administration. RJ powder was previously chemically characterized and given orally (50 or 100 mg of powder/kg b.w./day) by gastric gavage. The concentrations of amino acids (alanine, aspartic acid, gamma-aminobutyric acid, glutamic acid, histidine and taurine) in the brain regions examined (prefrontal cortex, hippocampus, striatum and hypothalamus) were quantified using HPLC. We also examined basic biochemical parameters of renal and hepatic activity, as damage of these organs could potentially explain the changes in brain function and behavior. Upon biochemical examination, a decrease in the concentration of gamma-aminobutyric acid was observed in both the striatum and hypothalamus. Liver and kidney functions were not changed by chronic RJ-administration. Our results provide insight toward understanding the mechanism of action of RJ and its effects on neurotransmission in the central nervous system.