The influence of propolis plus Hyoscyamus niger L. against COVID-19: A phase II, multicenter, placebo-controlled, randomized trial.

The incubation period of COVID-19 symptoms, along with the proliferation and high transmission rate of the SARS-CoV-2 virus, is the cause of an uncontrolled epidemic worldwide. Vaccination is the front line of prevention, and antiinflammatory and antiviral drugs are the treatment of this disease. In addition, some herbal therapy approaches can be a good way to deal with this disease. The aim of this study was to evaluate the effect of propolis syrup with Hyoscyamus niger L. extract in hospitalized patients with COVID-19 with acute disease conditions in a double-blinded approach. The study was performed on 140 patients with COVID-19 in a double-blind, randomized, and multicentral approach. The main inclusion criterion was the presence of a severe type of COVID-19 disease. The duration of treatment with syrup was 6 days and 30 CC per day in the form of three meals. On Days 0, 2, 4, and 6, arterial blood oxygen levels, C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell, as well as the patient's clinical symptoms such as fever and chills, cough and shortness of breath, chest pain, and other symptoms, were recorded and analyzed. Propolis syrup with H. niger L. significantly reduces cough from the second day, relieving shortness of breath on the fourth day, and significantly reduces CRP, weakness, and lethargy, as well as significantly increased arterial blood oxygen pressure on the sixth day compared to the placebo group (p < 0.05). The results in patients are such that in the most severe conditions of the disease 80% < SpO2 (oxygen saturation), the healing process of the syrup on reducing CRP and increasing arterial blood oxygen pressure from the fourth day is significantly different compared with the placebo group (p < 0.05). The use of syrup is associated with a reduction of 3.6 days in the hospitalization period compared with the placebo group. Propolis syrup with H. niger L. has effectiveness in the viral and inflammatory phases on clinical symptoms and blood parameters and arterial blood oxygen levels of patients with COVID-19. Also, it reduces referrals to the intensive care unit and mortality in hospitalized patients with COVID-19. So, this syrup promises to be an effective treatment in the great challenge of COVID-19.

Protective effects of nanocurcumin against stress-induced deterioration in the intestine.

The therapeutic activities of curcumin have long been investigated in some chronic and inflammatory diseases. This study was designed to investigate the protective effects of nanocurcumin on intestinal barrier function, apoptosis, and oxidative stress in rats exposed to traffic noise. Forty rats were divided into four groups: two traffic noise-exposed groups of animals that received either vehicle (NOISE) or nanocurcumin (NCUR + NOISE) and two control groups that either remained intact (CON) or received nanocurcumin (NCUR). Nanocurcumin injection (15 mg/Kg/ip) and traffic noise exposure were administered daily for two weeks. The relative protein expression of intestinal tight junctions, occludin, and ZO-1 and Bax/Bcl-2 ratio was measured to evaluate barrier integrity and apoptosis in intestinal samples, respectively. Plasma D-lactate concentration was examined as a criterion of intestinal permeability. Corticosterone, superoxide dismutase (SOD) activity, glutathione (GSH), total antioxidant capacity (TAC), and nitrite were measured in serum. The noise exposure increased Bax/Bcl-2 ratio, corticosterone, and oxidative stress in the NOISE animals. Nanocurcumin treatment improved the Bax/Bcl-2 ratio and reduced corticosterone and oxidative stress in the NCUR + NOISE animals. The expression of tight junction proteins was decreased while the concentration of D-lactate was increased in the NOISE animals. Nanocurcumin did not efficiently impact the expression of tight junction proteins and the D-lactate level in the NCUR + NOISE group. Nanocurcumin administration displayed antioxidant and anti-apoptotic roles in the noise-exposed rats, however, it did not affect the intestinal barrier integrity. We concluded that reduced apoptosis in the intestine might be related to the antioxidant activity of nanocurcumin and its modulatory effects on the HPA axis in the nanocurcumin-treated animals.

Lavandula angustifolia biological characteristics: An in vitro study.

OBJECTIVE: Lavender is an aromatic shrub belonging to the Lamiaceae family. The flowers and leaves in different forms of extracts are used as herbal medicine. The accumulation of amyloid beta (Aß) plaques, reduction of acetylcholine due to hyperactivity of acetylcholinesterase, and glutamate neurotoxicity are known to be involved in decreased level of cognitive function. In our previous study, we proved that the aqueous extract of lavender improves learning and memory. This in vitro study was designed to evaluate antiaggregative, antioxidant, and antiacetylcholinesterase activities of the herbal medicine. METHODS: Thin layer chromatography, high-performance liquid chromatography, thioflavin, atomic force microscope (AFM), Elleman,and 2,2-diphenyl-1-picryl hydrazyl techniques were used for qualitative analysis, quantitative analysis, antiaggregative characteristics, anti-acetylcholinestrase activity and antioxidant activity of the lavender extract, respectively. RESULTS: We found chromatographic peaks of caffeic acid and luteolin-7-glycosid in the lavender extract. Our results indicated that aqueous extract of lavender dose-dependently inhibits the formation of Aß aggregate. The AFM technique showed that lavender largely diminished the Aß fibril formation. We also observed a considerable radical scavenging activity of the extract. CONCLUSIONS: Prevention of Aß plaque formation and antioxidant activity along with nontoxic features of the lavender extract promise possible effectiveness of this plant on improving some neurological disorders including Alzheimer's disease.

Effect of probiotic supplementation on seizure activity and cognitive performance in PTZ-induced chemical kindling.

Epilepsy is one of the most common neurological disorders that severely affect life quality of many people worldwide. Ion transport in the neuronal membrane, inhibitory-excitatory mechanisms, and regulatory modulator systems have been implicated in the pathogenesis of epilepsy. A bidirectional communication is proposed between brain and gut where the brain modulates the gastrointestinal tract, and the gut can affect brain function and behavior. The gut microbiome takes an important role in health and disease where dysbiosis is involved in several neurological disorders. Probiotics as living microorganisms are beneficial to humans and animals when adequately administered. In the present work, we evaluated the effect of a probiotic bacteria mixture on seizure activity, cognitive function, and gamma-aminobutyric acid (GABA), nitric oxide (NO), malondealdehyde (MDA), and total antioxidant capacity (TAC) level of the brain tissue in the pentylenetetrazole (PTZ)-induced kindled rats. The Racine score and performance in water maze were considered as indices of the epileptic severity and the spatial learning and memory, respectively. We found that the probiotic supplementation substantially reduces seizure severity so that almost no probiotic-treated animals showed full kindling. The oral bacteriotherapy partially improved the spatial learning and memory in the kindled rats. The intervention decreased NO and MDA and increased TAC concentration of the brain. The probiotic treatment also increased the inhibitory neurotransmitter GABA. Our findings are the first preclinical report to show positive effect of probiotic bacteria on seizure-induced neurological disorders. Further investigation is required to answer the questions raised about the probable mechanisms involved.

The Effects of Probiotic Supplementation on Gene Expression Related to Inflammation, Insulin, and Lipids in Patients With Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Limited data are available assessing the effects of probiotic supplementation on gene expression related to inflammation, insulin, and lipids in patients with multiple sclerosis (MS). OBJECTIVES: The current study was conducted to assess the effects of probiotic supplementation on gene expression related to inflammation, insulin, and lipids in patients with MS. METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed among 40 patients with MS. Participants were randomly assigned into two groups to receive either a probiotic capsule containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 colony-forming units/g each; n = 20) or placebo (n = 20) for 12 weeks. Gene expression related to inflammation, insulin, and lipids was quantified in blood samples of patients with MS with the reverse transcription polymerase chain reaction (RT-PCR) method. RESULTS: We found that compared with placebo, probiotic supplementation down-regulated gene expression of interleukin-8 (IL-8; p < 0.001) and tumor necrosis factor-alpha (TNF-α) mRNA (p < .001) in peripheral blood mononuclear cells of patients with MS. We did not observe any significant effect of probiotic supplementation on gene expression of interleukin-1 (IL-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), or oxidized low-density lipoprotein receptor (LDLR) in peripheral blood mononuclear cells of patients with MS. CONCLUSIONS: Overall, probiotic supplementation for 12 weeks in patients with MS significantly improved gene expression of IL-8 and TNF-α but did not influence IL-1, PPAR-γ, or LDLR.

Prenatal exposure to noise stress: anxiety, impaired spatial memory, and deteriorated hippocampal plasticity in postnatal life.

Sound pollution is known as an annoying phenomenon in modern life. Especially, development of organisms during fetal life is more sensitive to environmental tensions. To address a link between the behavioral and electrophysiological aspects of brain function with action of hypothalamus-pituitary-adrenal (HPA) axis in stressed animals, this study was carried out on the male Wistar rats prenatally exposed to sound stress. Groups of pregnant rats were exposed to noise stress for 1, 2, and 4 hour(s). The degree of anxiety and the spatial memory were evaluated by elevated plus maze and Morris water maze, respectively. Basic synaptic activity and long-term potentiation (LTP) induction were assessed in the CA3-CA1 pathway of hippocampus. The serum level of corticosterone was measured in the pregnant mothers and the offspring. The behavioral experiments appeared that the stressed animals performed considerably weaker than the control rats. The prenatal stress negatively affected the basic synaptic responses and led to a lower level of LTP. The pregnant animals showed an increased serum corticosterone in comparison with the nonpregnant females. Also the offspring exposed to the noise stress had a more elevated level of corticosterone than the control rats. Our findings indicate that the corticosterone concentration changes markedly coincides the results of behavioral and electrophysiological experiments. We conclude that, similar to other environmental stresses, the sound stress during fetal life efficiently disturbs both cognitive abilities and synaptic activities. The changes in action of HPA axis may contribute to problems of the brain function in the prenatally stress exposed animals.

Vitamin D supplementation restores suppressed synaptic plasticity in Alzheimer's disease.

OBJECTIVES: Hippocampus, an appropriate area of brain for assessment of long-term potentiation (LTP), has been found to be susceptible to neural damages caused by Alzheimer's disease. Evidence indicates that vitamin D supports nerve transmission and synaptic plasticity. Vitamin D receptors are expressed in the hippocampus. METHODS: The present study evaluates occurrence of LTP in the control (CON) group fed with normal regimen and, three groups of Aß-treated rats taking normal (ALZ), vitamin D-free (ALZ - D), or 1,25(OH)2D3 supplemented (ALZ + D) food regimens. In in vivo experiments pre- and post-tetanus field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA3-CA1 pathway. RESULTS: We found that the amplitude of baseline fEPSPs was significantly lower in the ALZ group compared with the CON one; lack of vitamin D further declined the amplitude of responses in the ALZ - D animals. While the tetanic stimulation elicited a considerable LTP in the CON rats it was failed to induce LTP in the ALZ animals. Furthermore, the tetanus considerably depressed the amplitude of recordings in the ALZ - D group. 1,25(OH)2D3 supplementation restored post-tetanus potentiation of fEPSPs amplitude in the ALZ + D groups. DISCUSSION: The present findings signify the crucial role of vitamin D on the basic synaptic transmission and synaptic plasticity.

What we need to know about the germ-free animal models.

The gut microbiota (GM), as a forgotten organ, refers to the microbial community that resides in the gastrointestinal tract and plays a critical role in a variety of physiological activities in different body organs. The GM affects its targets through neurological, metabolic, immune, and endocrine pathways. The GM is a dynamic system for which exogenous and endogenous factors have negative or positive effects on its density and composition. Since the mid-twentieth century, laboratory animals are known as the major tools for preclinical research; however, each model has its own limitations. So far, two main models have been used to explore the effects of the GM under normal and abnormal conditions: the isolated germ-free and antibiotic-treated models. Both methods have strengths and weaknesses. In many fields of host-microbe interactions, research on these animal models are known as appropriate experimental subjects that enable investigators to directly assess the role of the microbiota on all features of physiology. These animal models present biological model systems to either study outcomes of the absence of microbes, or to verify the effects of colonization with specific and known microbial species. This paper reviews these current approaches and gives advantages and disadvantages of both models.

Erythropoietin improves spatial learning and memory in streptozotocin model of dementia.

Alzheimer's disease is associated to impairments of learning and memory. Because studies demonstrated that erythropoietin has positive effects on central nervous system, the aim of this study was to evaluate the effect of erythropoietin on spatial learning and memory in a well defined model for Alzheimer's disease. Rat model of Alzheimer's was created by injecting streptozotocin in lateral ventricles of the brain. Two weeks later, the rats were assessed through passive avoidance learning test to confirm the induction of Alzheimer's. After that, they received erythropoietin (5000IU/kg) every other day, for two weeks and then spatial learning and memory were assessed by a 5-day protocol of Morris water maze test in them. The results showed that streptozotocin severely damaged learning and memory in rats. Erythropoietin had no significant effect in the control rats; however, it significantly improved learning and memory in rats with Alzheimer's disease, as the task performance of the rats treated with erythropoietin was like the control group. The results suggest that erythropoietin can be considered as an effective treatment for neurodegenerative damages.

Effect of postnatal environmental enrichment on LTP induction in the CA1 area of hippocampus of prenatally traffic noise-stressed female rats.

Early-life stress negatively alters mammalian brain programming. Environmental enrichment (EE) has beneficial effects on brain structure and function. This study aimed to evaluate the effects of postnatal environmental enrichment on long-term potentiation (LTP) induction in the hippocampal CA1 area of prenatally stressed female rats. The pregnant Wistar rats were housed in a standard animal room and exposed to traffic noise stress 2 hours/day during the third week of pregnancy. Their offspring either remained intact (ST) or received enrichment (SE) for a month starting from postnatal day 21. The control groups either remained intact (CO) or received enrichment (CE). Basic field excitatory post-synaptic potentials (fEPSPs) were recorded in the CA1 area; then, LTP was induced by high-frequency stimulation. Finally, the serum levels of corticosterone were measured. Our results showed that while the prenatal noise stress decreased the baseline responses of the ST rats when compared to the control rats (P < 0.001), the postnatal EE increased the fEPSPs of both the CE and SE animals when compared to the respective controls. Additionally, high-frequency stimulation (HFS) induced LTP in the fEPSPs of the CO rats (P < 0.001) and failed to induce LTP in the fEPSPs of the ST animals. The enriched condition caused increased potentiation of post-HFS responses in the controls (P < 0.001) and restored the disrupted synaptic plasticity of the CA1 area in the prenatally stressed rats. Likewise, the postnatal EE decreased the elevated serum corticosterone of prenatally stressed offspring (P < 0.001). In conclusion, the postnatal EE restored the stress induced impairment of synaptic plasticity in rats' female offspring.

The microbiota-gut- hippocampus axis.

Introduction: It is well known that the intestinal bacteria substantially affect physiological processes in many body organs. Especially, through a bidirectional communication called as gut-microbiota-brain axis, the gut microbiota deeply influences development and function of the nervous system. Hippocampus, as a part of medial temporal lobe, is known to be involved in cognition, emotion, and anxiety. Growing evidence indicates that the hippocampus is a target of the gut microbiota. We used a broad search linking the hippocampus with the gut microbiota and probiotics. Methods: All experimental studies and clinical trials published until end of 2021 were reviewed. Influence of the gut microbiota on the behavioral, electrophysiological, biochemical and histological aspects of the hippocampus were evaluated in this review. Results: The effect of disrupted gut microbiota and probiotic supplements on the microbiota-hippocampus link is also considered. Studies show that a healthy gut microbiota is necessary for normal hippocampus dependent learning and memory and synaptic plasticity. The known current mechanisms are production and modulation of neurotrophins, neurotransmitters and receptors, regulation of intracellular molecular processes, normalizing the inflammatory/anti-inflammatory and oxidative/antioxidant factors, and histological stability of the hippocampus. Activity of the hippocampal neuronal circuits as well as behavioral functions of the hippocampus positively respond to different mixtures of probiotic bacteria. Discussion: Growing evidence from animal researches indicate a close association between the hippocampus with the gut microbiota and probiotic bacteria as well. However, human studies and clinical trials verifying such a link are scant. Since the most of papers on this topic have been published over the past 3 years, intensive future research awaits.

Good bacteria, oxidative stress and neurological disorders: Possible therapeutical considerations.

Although oxidative agents such as free radicals can fight pathogens, an imbalance of oxidant/anti-oxidant activity can lead to harmful effects in our body known as oxidative stress. Various cellular organelles produce oxidative agents as well as anti-oxidants. The main oxidative stressors are classified under the free radical species; reactive oxygen species and reactive nitrogen species. On the other hand, superoxide dismutase, glutathione peroxidase, catalase and Glutathione are the main enzymatic mechanisms against oxidations. Gut microbiota with trillions of beneficial bacteria plays a considerable role in the production of anti-oxidants. Emerging evidence indicates an association between damaged intestinal flora and oxidative stress. Probiotics as beneficial bacteria are shown to restore damaged intestinal microbiota. Extensive evidence indicates the helpful effects of probiotics on the balance of anti-oxidant/oxidant agents. Since oxidative stressors play an important role in the development of some neurological disorders, intestinal microbiota modification and probiotic supplements are considered as suggested treatments to prevent or even relieve symptoms in the brain diseases. This review considers the beneficial effect of the gut and probiotic bacteria in either fighting the oxidative factors or producing the anti-oxidative biomarkers.

Nanocurcumin substantially alleviates noise stress-induced anxiety-like behavior: The roles of tight junctions and NMDA receptors in the hippocampus.

Environmental noise stress affects non-auditory brain regions such as the hippocampus; an area of the brain implicated in cognition and emotion. Recent experimental data indicate that dysfunction of the blood-brain barrier (BBB) and overexpression of NMDA receptors may cause anxiety. In this experiment, we evaluated the effect of nanocurcumin on anxiety-like behavior and the expression of tight junctions and NMDA receptor subunits in the hippocampus of rats exposed to traffic noise. Forty rats were assigned to control (CON), stress (ST), nanocurcumin (NC), and nanocurcumin+stress (NC+ST) groups. Anxiety-like behavior was evaluated through an elevated zero maze apparatus. The gene expression of tight junctions and NMDA receptor subunits was examined by real-time PCR in the hippocampus. Statistical analysis showed that noise exposure developed anxiety-like behavior and elevated the corticosterone level in the ST group compared to the CON group. The nanocurcumin administration decreased the stress and anxiety in the NC+ST group compared to the ST animals. While the noise stress reduced the gene expression of tight junctions occludin, claudin-5, and ZO-1, the nanocurcumin administration increased them in the NC+ST animals. Furthermore, the noise stress elevated the gene expression of the NMDA receptor subunits GRIN1 and GRIN2B. The NC+ST animals showed a modification of these subunits compared to the ST animals. Our findings showed that noise exposure promotes stress and anxiety and impairs the NMDA receptor structure and BBB integrity. The nanocurcumin treatment partly restores the destructive effects of noise exposure.

Effects of nano-curcumin on noise stress-induced hippocampus-dependent memory impairment: behavioral and electrophysiological aspects.

BACKGROUND: Noise pollution is one of the fundamental factors in the etiology of many disorders. Noise stress adversely affects cognitive behaviors and long-term potentiation (LTP), the candidate mechanism of learning and memory. In the present study, we examined the neuroprotective effects of nano-curcumin on behavioral and electrophysiological aspects of hippocampus-dependent memory in noise-exposed animals. METHODS: The stressed animals received either vehicle (ST) or nano-curcumin (NANO + ST) for 2 weeks. The control groups remained either intact (CON) or received nano-curcumin (NANO + CON). The ST and NANO + ST groups were exposed to daily noise for 2 weeks. The spatial memory was assessed in the Morris water maze. The LTP was investigated through field potential recording in the CA3-CA1 pathway of the hippocampus. Serum corticosterone level was measured at the end of the experiments. RESULTS: The ST group showed a lower cognitive function and suppressed LTP compared to the CON group. The nano-curcumin treatment improved the maze navigation and LTP induction compared to the ST group. While the stress exposure elevated the serum level of corticosterone in the ST animals, nano-curcumin treatment reduced it. CONCLUSIONS: The nano-curcumin treatment restores impaired behavioral and electrophysiological aspects of learning and memory in the noise-exposed animals. The plasma corticosterone levels may be associated with changes in cognitive behavior and synaptic plasticity.

Vitamin-D-free regimen intensifies the spatial learning deficit in Alzheimer's disease.

Evidences support a link between nutrition and risk of neurodegenerative Alzheimer's disease (AD). This work was designed to find out if food regimens lacking vitamin D or with a supplement of vitamin D could affect spatial performances in the Alzheimeric animals. The experiment was done on the control and Alzheimeric (ALZ) animals on a normal regimen of food, as well as the Alzheimeric rats fed with regimens lacking vitamin D (ALZ-D) or supplemented with 1,25(OH)2D3 (ALZ+D). For learning the spatial task the animals were trained to locate a hidden platform in the Morris water maze. We found that the ALZ rats had an obvious lower performance compared with the control ones. Generally, the ALZ-D rats displayed a poorer spatial learning compared with either the ALZ or the ALZ+D rats. Vitamin D supplement did not significantly influence the spatial performance. We conclude that although vitamin D deficiency strengthens the spatial learning deficit in AD, a supplement of 1,25(OH)2D3 does not effectively underlie the maze performance. It can be concluded that subjects with AD must be protected from vitamin D inadequacy.

Interplay of Good Bacteria and Central Nervous System: Cognitive Aspects and Mechanistic Considerations.

The human gastrointestinal tract hosts trillions of microorganisms that is called "gut microbiota." The gut microbiota is involved in a wide variety of physiological features and functions of the body. Thus, it is not surprising that any damage to the gut microbiota is associated with disorders in different body systems. Probiotics, defined as living microorganisms with health benefits for the host, can support or restore the composition of the gut microbiota. Numerous investigations have proved a relationship between the gut microbiota with normal brain function as well as many brain diseases, in which cognitive dysfunction is a common clinical problem. On the other hand, increasing evidence suggests that the existence of a healthy gut microbiota is crucial for normal cognitive processing. In this regard, interplay of the gut microbiota and cognition has been under focus of recent researches. In the present paper, I review findings of the studies considering beneficial effects of either gut microbiota or probiotic bacteria on the brain cognitive function in the healthy and disease statuses.

Alzheimer's disease treatment: The share of herbal medicines.

One of the most frequent forms of dementia in neurological disorders is Alzheimer's disease (AD). It is a chronic neurodegenerative disease characterized by impaired learning and memory. Pathological symptoms as extracellular amyloid-beta (Aß) plaques and intracellular accumulation of neurofibrillary tangles occur in AD. Due to the aging of the population and increased prevalence of AD, discovery of new therapeutic agents with the highest effectiveness and fewer side effect seems to be necessary. Numerous synthetic medicines such as tacrine, donepezil, galantamine, rivastigmine, memantine, glutathione, ascorbic acid, ubiquinone, ibuprofen, and ladostigil are routinely used for reduction of the symptoms and prevention of disease progression. Nowadays, herbal medicines have attracted popular attention for numerous beneficial effects with little side effects. Lavandula angustifolia, Ginkgo biloba, Melissa officinalis, Crocus sativus, Ginseng, Salvia miltiorrhiza, and Magnolia officinalis have been widely used for relief of symptoms of some neurological disorders. This paper reviews the therapeutic effects of phytomedicines with prominent effects against various factors implicated in the emergence and progression of AD.

Light deprivation improves melatonin related suppression of hippocampal plasticity.

In early postnatal life, sensory inputs deeply influence development as well as function of the brain. Plasticity of synaptic transmission including its experimentally induced form, long-term potentiation (LTP), is affected by sensory deprivation in neocortex. This study is devoted to assess if dark rearing and a dark phase synthesized hormone melatonin influence LTP in the hippocampus, an area of brain involved in learning and memory. In vivo experiments were carried out on two groups of 45-days-old male Wistar rats kept in standard 12-h light/dark condition [light reared (LR) tested during the light phase] or in complete darkness [dark reared (DR)] since birth to testing. Each group, in turn, was divided to two, vehicle- and melatonin-treated, groups. Stimulating the Schaffer collaterals of CA3 area of hippocampus extracellular postsynaptic potentials (EPSPs) were recorded in the CA1 area. Having the stable baseline responses to the test pulses, the hippocampus was perfused by either vehicle or 2 microg melatonin and EPSPs were recorded for 30 min. Then, for induction of LTP, the tetanus was applied to the Schaffer collaterals and the field potentials were pooled for 120-min post-tetanus. The light deprivation resulted in a significant augmentation in the amplitude of baseline responses. Also, we observed a melatonin-induced increase in amplitude of the baseline recordings in either LR or DR animals. Tetanic stimulation elicited LTP of EPSPs in both LR and DR groups, robustly in the former where it lasted for about 90 min. Generally, melatonin inhibited the production of LTP in the two groups especially in the LR animals leading to a noticeable depression. We concluded that higher level of neuronal activity in the DR rats gives rise to a lower level of LTP. Weaker effect of melatonin on blocking the potentiation of post-tetanus EPSPs in the DR rats may be the result of a desensitization of melatonin receptors due to chronically increased levels of this hormone in the visually deprived rats.

Environmental enrichment restores impaired spatial memory and synaptic plasticity in prenatally stress exposed rats: The role of GABAergic neurotransmission.

Evidence shows that prenatal stress negatively affects cognitive functions and activity of neuronal circuits in postnatal age. Environmental enrichment counteracts deficits induced by early life stress. We examined if behavioural function and synaptic plasticity are sensitive to prenatal stress and, how much environmental enrichment and GABAergic system impact these phenomena. Animals were exposed to noise stress during the third trimester of foetal life. Groups of the stressed animals remained intact (S-SH) or received enrichment (S-EE) from postnatal day 22 for one month. Also, two groups received either saline (S-SH-S) or bicuculline (S-SH-B). One enriched group received muscimol (S-EE-M). The control groups were intact (C-SH), enriched (C-EE), or received bicuculline (C-SH-B) or saline (C-SH-S). We assessed learning and memory and, hippocampal long-term potentiation (LTP). Serum corticosterone levels were detected as a measure of stress condition. We found that stress reduced spatial performance and suppressed LTP in the S-SH animals. Postnatal enrichment restored both spatial learning and memory and synaptic plasticity in the S-EE rats. GABAergic antagonism strengthens maze performance and LTP induction in the S-SH-B group. However, muscimol prevented the positive effects of enrichment in the S-EE-M animals. Environmental enrichment and GABAergic modulation may improve disrupted spatial performance and synaptic plasticity.