Underlying mechanisms behind the neuroprotective effect of vanillic acid against diabetes-associated cognitive decline: An in vivo study in a rat model.

Hippocampal synaptic dysfunction, oxidative stress, neuroinflammation, and neuronal loss play critical roles in the pathophysiology of diabetes-associated cognitive decline (DACD). The study aimed to investigate the effects of vanillic acid (VA), a phenolic compound, against DACD and explore the potential underlying mechanisms. Following confirmation of diabetes, rats were treated with VA (50 mg/kg/day; P.O.) or insulin (6 IU/rat/day; S.C.) for 8 consecutive weeks. The cognitive performance of the rats was evaluated using passive-avoidance and water-maze tasks. Long-term potentiation (LTP) was induced at hippocampal dentate gyrus (DG) synapses in response to high-frequency stimulation (HFS) applied to the perforant pathway (PP) to evaluate synaptic plasticity. Oxidative stress factors, inflammatory markers, and histological changes were evaluated in the rat hippocampus. This study showed that streptozotocin (STZ)-induced diabetes caused cognitive decline that was associated with inhibition of LTP induction, suppression of enzymatic antioxidant activities, enhanced lipid peroxidation, elevated levels of inflammatory proteins, and neuronal loss. Interestingly, chronic treatment with VA alleviated blood glucose levels, improved cognitive decline, ameliorated LTP impairment, modulated oxidative-antioxidative status, inhibited inflammatory response, and prevented neuronal loss in diabetic rats at a level comparable to insulin therapy. The results suggest that the antihyperglycemic, antioxidative, anti-inflammatory, and neuroplastic properties of VA may be the mechanisms behind its neuroprotective effect against DACD.

Parkinson's disease tremor prediction using EEG data analysis-A preliminary and feasibility study.

PURPOSE: Tremor is one of the hallmarks of Parkinson's disease (PD) that does not respond effectively to conventional medications. In this regard, as a complementary solution, methods such as deep brain stimulation have been proposed. To apply the intervention with minimal side effects, it is necessary to predict tremor initiation. The purpose of the current study was to propose a novel methodology for predicting resting tremors using analysis of EEG time-series. METHODS: A modified algorithm for tremor onset detection from accelerometer data was proposed. Furthermore, a machine learning methodology for predicting PD hand tremors from EEG time-series was proposed. The most discriminative features extracted from EEG data based on statistical analyses and post-hoc tests were used to train the classifier for distinguishing pre-tremor conditions. RESULTS: Statistical analyses with post-hoc tests showed that features such as form factor and statistical features were the most discriminative features. Furthermore, limited numbers of EEG channels (F3, F7, P4, CP2, FC6, and C4) and EEG bands (Delta and Gamma) were sufficient for an accurate tremor prediction based on EEG data. Based on the selected feature set, a KNN classifier obtained the best pre-tremor prediction performance with an accuracy of 73.67%. CONCLUSION: This feasibility study was the first attempt to show the predicting ability of EEG time-series for PD hand tremor prediction. Considering the limitations of this study, future research with longer data, and different brain dynamics are needed for clinical applications.

Mitochondrial biogenesis and apoptosis as underlying mechanisms involved in the cardioprotective effects of Gallic acid against D-galactose-induced aging.

BACKGROUND: Aging is a main risk factor for the development of cardiovascular diseases (CVDs). Gallic acid (GA) is a phenolic compound derived from a wide range of fruits. GA has a wide spectrum of pharmacological properties, including anti-oxidative, anti-inflammatory, and cardioprotective effects. This research was conducted to determine the cardioprotective effect of GA on cardiac hypertrophy in aged rats. METHODS AND RESULTS: Following histological evaluation and through observing the heart, we found that GA improved the cardiac hypertrophy induced by D-galactose (D-GAL) in cardiac cells. To clarify the causes for this anti-aging effect, we evaluated the malonic dialdehyde levels and antioxidant enzyme activity in rat cardiac tissue. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK-MB) in serum were measured. The levels of genes related to mitochondrial biogenesis, mitophagy, and apoptosis in cardiac tissue were surveyed. The findings represented that GA ameliorated antioxidant enzyme activity while significantly decreasing the malonic dialdehyde levels. Real-time PCR analysis proposed that GA effectively improved mitochondrial biogenesis in the heart via regulating the expression levels of Sirtuin 1 (SIRT1), PPARγ coactivator 1α (PGC1-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). GA also mitigated apoptosis in the heart by modulating the expression levels of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X (Bax). In addition, GA improved serum LDH and CK-MB levels. CONCLUSIONS: GA may alleviate aging-induced cardiac hypertrophy via anti-oxidative, mitoprotective, and anti-apoptotic mechanisms.

Association of vitamin A and its organic compounds with stroke - a systematic review and meta-analysis.

PURPOSE: The main purpose of this systematic review was to evaluate the association between the stroke (risk of stroke and the mortality due to stroke) and vitamin A, its organic compounds and its provitamins. METHOD: Major databases including PubMed, Scopus, and Web of Science were searched. Studies with human samples were included for risk assessment. The association was assessed using odds ratio (log(OR)) and a random-effect model. I2 statistic, variance (tau2) and prediction interval were used for heterogeneity assessment. The funnel plot was used for publication bias. RESULTS: Twenty-one studies including 5789 stroke patients were retrieved. Twenty studies had sufficient information for quantitative analyses. The pooled effect showed an inverse association between vitamin A and its organic compound with the risk of stroke (log(OR) = -0.46 95%CI (-0.81;-0.12)) and with the risk of mortality due to stroke (log(OR) = -0.39 95%CI (-0.74;-0.04)). However, according to subgroup analyses, the association was dependent on the compound in a way that retinol and beta-carotene were the most effective compounds. The effects of several confounding factors and the threshold levels for vitamin A and its organic compound on the effectiveness were discussed. CONCLUSION: Insufficiency of retinol and beta-carotene significantly increased the risk of stroke; however, due to heterogeneity between studies more studies are needed for evaluating clinical significance of this outcome.

The role of mGlu4 receptors within the nucleus accumbens in acquisition and expression of morphine-induced conditioned place preference in male rats.

BACKGROUND: Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP). In addition, metabotropic glutamate receptors (mGluRs) in NAc play important roles in the reward pathways. However, the precise role of mGluR4 in different steps of the morphine-induced CPP is less well known. In the present study the effect of bilateral intra-accumbal infusion of VU0155041, as a specific mGluR4 agonist on the acquisition and expression of morphine induced CPP in male Wistar rats was investigated. The animals were bilaterally implanted with guide cannulae above the NAc. In the first step of the study, the VU0155041 was administered at doses of 10, 30 and 50 µg/0.5 µL saline per side into the NAc during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase of morphine-induced CPP. In the second step of the study, the rats bilaterally received VU0155041 at the dose of 50 µg/0.5 µL, 5 min before the post-conditioning test in order to check the effect of VU0155041 on the expression of morphine-induced CPP. RESULTS: The results showed that the intra-accumbal injection of VU0155041 inhibits the acquisition of morphine-induced CPP in a dose dependent manner, but had no effect on expression. CONCLUSIONS: The data indicated that intra-NAc administration of VU0155041 dose dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine. These effects may be related to changes in glutamate activity in the NAC and/or learning dependent mechanism of glutamate neurotransmission in reward pathway(s).

The effect of the mGlu8 receptor agonist, (S)-3,4-DCPG on acquisition and expression of morphine-induced conditioned place preference in male rats.

BACKGROUND: The nucleus accumbens (NAc) plays a principal role in drug reward. It has been reported that metabotropic glutamate receptors (mGlu receptors) play a key role in the rewarding pathway(s). Previous studies have shown the vast allocation of the different types of mGlu receptors, including mGlu8 receptors, in regions that are associated with opioid rewards, such as the NAc. The aim of the present study was to evaluate the role of mGlu8 receptors within the NAc in the acquisition and expression phases of morphine induced conditioned place preference (CPP). Adult male Wistar rats were bilaterally implanted by two cannulas' in the NAc and were evaluated in a CPP paradigm. Selective mGlu8 receptor allosteric agonist (S-3,4-DCPG) was administered at doses of 0.03, 0.3, and 3 µg/0.5 µL saline per side into the NAc on both sides during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase, or before place preference test, or post-conditioning (expression) phase of morphine-induced CPP. RESULTS: The results revealed that intra-accumbal administration of S-3,4-DCPG (0.3 and 3 µg) markedly decreased the acquisition in a dose-dependent manner but had no effect on expression of morphine-induced CPP. CONCLUSIONS: The findings suggest that activation of mGlu8 receptors in the NAc dose-dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine which may be related to the glutamate activity into the NAc and in reward pathway(s). These data suggest that mGlu8 receptor may be involved in conditioned morphine reward.

Pretraining hippocampal stimulation of melatonin type 2 receptors can improve memory acquisition in rats.

BACKGROUND: Learning and memory are among the most important cognitive functions of the brain. Melatonin receptor type 2 (MT2R) is located in the hippocampus and participates in learning and memory processes. In the present study, we examined the role of hippocampal MT2R activation in the acquisition, consolidation, and retrieval of learning and memory in novel object recognition (NOR) and passive avoidance (PA) tasks. METHODS: IIK7 (0.03, 0.3, and 3 µg/µl/side), as a selective MT2R agonist, or vehicle was injected bilaterally into the dentate gyrus (DG) region of the hippocampus in rats five minutes before training, immediately after training, and five minutes before the retrieval-behavioral tasks, respectively. The discrimination index (DI) was measured in the NOR task, while step-through latency in acquisition (STLa), number of trials to acquisition (NOT), step-through latency in the retention trial (STLr), and time spent in the dark compartment (TDC) were determined in the PA task. RESULTS: The pretraining intrahippocampal injection of IIK7 at all doses significantly improved acquisition in the PA task. On the other hand, the posttraining intrahippocampal administration of IIK7 had no significant effects on consolidation. The preretrieval intrahippocampal injection of IIK7 at different doses attenuated the retrieval of memory. However, the NOR data showed that the intrahippocampal injection of IIK7 at different doses had no significant effects on the acquisition, consolidation, or retrieval in this task. DISCUSSION: Based on the findings, stimulation of MT2R could improve acquisition, whereas it had no effects on consolidation. It could impair retrieval in the PA task, while it had no effects on object recognition in rats.

Microinjection of the mGluR2/3 agonist, LY379268, into the nucleus accumbens attenuates extinction latencies and the reinstatement of morphine-induced conditioned place preference in rats.

Previous studies indicate that metabotropic glutamate receptor type 2/3 (mGluR2/3) has a key role in the rewarding properties of morphine-induced conditioning place preference (CPP). Group II mGluR2/3 agonists are offered as a drug addiction treatment. The nucleus accumbens (NAc), which is one of the important areas involved in the reward circuitry, also expresses these receptors. In this study, we evaluated the effects of mGluR2/3 agonist, LY379268, on the extinction and reinstatement of morphine-induced CPP, following its microinjection into the NAc. Adult male Wistar rats (220-250 g) were implanted bilaterally by two separate cannulae into the NAc. After the acquisition of morphine CPP, different doses of LY379268 (0.3, 1 and 3 µg/0.5 µl saline) were microinjected into the NAc every day during the extinction period and, in a different set of experiments, on the reinstatement test day, 60 min before the infusion of a priming dose of morphine (1 mg/kg; subcutaneous). Thereafter, the animals were tested for place preference by the Ethovision software. The intra-accumbal injection of the mGluR2/3 agonist, LY379268, significantly decreased the extinction latencies and reinstatement of morphine-induced CPP at higher doses. It seems that the NAc might be a functional region for mGluR2/3 to play a regulatory role for decreasing drug-seeking behavior in rats. Furthermore, it can be said that mGluR2/3 agonists have a potential role in the treatment of drug-seeking behaviors.

Effect of garlic powder on hippocampal long-term potentiation in rats fed high fat diet: an in vivo study.

The objective of this study was to determine the relation between the chronic consumption of garlic powder in combination with high-fat diet (HFD) on long term potentiation (LTP) in the dentate gyrus (DG) of rat hippocampus. Male rats were divided to 4 groups, control with the standard diet, control with a standard diet plus garlic, high-fat diet (HFD) group and high-fat diet with garlic. Following 6 months of controlled dietary in each experimental group, the rats were anesthetized with i.p. injection of ketamine and xylazin (100 and 2.5 mg/kg, respectively), and placed into a stereotaxic apparatus for surgery, electrode implantation and field potential recording. The population spike (PS) amplitude and slope of excitatory post synaptic potentials (EPSP) were measured in the DG area of adult rats in response to stimulation applied to the perforant path (PP) (by 400 Hz tetanization). The results showed that garlic increased EPSP slope and PS amplitude respect to HFD group. It was suggested that the garlic powder administration could attenuate the deteriorating effect of HFD on in vivo hippocampal LTP in the granular cells of the DG.

Influence of hippocampal GABAB receptor inhibition on memory in rats with acute ß-amyloid toxicity.

The neurotransmitter γ-aminobutyric acid (GABA) is involved in the process of memory. It has been reported that the inhibition of GABAB receptors has beneficial effects on cognition. The aim of this study was to investigate the role of CGP35348 (a GABAB receptor antagonist) on dentate gyrus GABAB receptor inhibition and its effects on learning and memory impairments that had been induced in adult male rats by microinjection of ß-amyloid (Aß). Seventy Wistar male rats were randomly divided into seven groups: control, sham (receiving the Aß vehicle only), Aß, Aß + CGP35348 (1, 10, and 100 µg/µL), and CGP35348 alone (10 µg/µL). Memory impairment was induced by unilateral interventricular microinjection of Aß (6 µg/6 µL). Rats were cannulated bilaterally in the dentate gyrus, and then, they were treated for 20 consecutive days. Learning and memory were assessed using the novel object recognition and passive avoidance learning tests. The discrimination index and the step-through latency were significantly increased in the Aß + CGP35348 group in comparison to the Aß only group (P < 0.05 and P < 0.01, respectively). Data showed that the discrimination index was decreased in the Aß + CGP35348 group in comparison with the control group (P < 0.05) and sham group (P < 0.01). Moreover, the step-through latency was significantly decreased in the Aß + CGP35348 group in comparison to the control and sham groups (P < 0.01). Data from this study indicated that intra-hippocampal microinjection of the GABAB receptor antagonist counteracts the learning, memory, and cognitive impairments induced by Aß. It can be concluded that the GABAB receptor antagonist is a possible therapeutic agent against the progression of acute Aß toxicity-induced memory impairment.

Effects of Hypericum Scabrum extract on anxiety and oxidative stress biomarkers in rats fed a long-term high-fat diet.

The continuous and long-term consumption of a high-fat diet (HFD) leads to weight gain and obesity. A HFD and obesity increase the risks of psychiatric disorders, such as anxiety and depression. In this study, we investigated the effects of a Hypericum Scabrum (H. scabrum) extract, which is an antioxidant, on anxiety in rats fed a long-term HFD. Sixty male Wistar rats were divided into the following six groups: (1) Control (standard diet), (2) Ext100 [standard diet supplemented with extract (100 mg/kg once/day)], (3) Ext300 [standard diet supplemented with extract (300 mg/kg once/day)], (4) HFD, (HFD), (5) HFD + Ext100, and (6) HFD + Ext300. The groups were fed their diet for 3 months. Anxiety was measured with the elevated plus-maze test. At the end of the study, blood samples were taken, and biochemical parameters and oxidative stress biomarker levels were determined in the plasma. Compared to the control group, the HFD group exhibited significant decreases in both the time in the open arms and number of entries into the open arms. H. scabrum extract supplementation significantly increased these parameters in the HFD-fed groups. The HFD significantly increased serum malondialdehyde levels and significantly decreased total glutathione levels, while H. scabrum extract supplementation significantly reversed these parameters. In conclusion, these results showed that a HFD increased anxiety behavior. In contrast, H. scabrum extract supplementation had anxiolytic effects and reversed the effects of the HFD, which suggested that the effects of H. scabrum extract supplementation were due to its strong antioxidant properties.

Role of group II metabotropic glutamate receptors (mGluR2/3) blockade on long-term potentiation in the dentate gyrus region of hippocampus in rats fed with high-fat diet.

In the hippocampus, metabotropic glutamate receptors (mGluRs) are involved in various forms of synaptic plasticity. High-fat diets (HFDs) adversely influence hippocampal structure and function and induce changes in hippocampal glutamate metabolism and neurotransmission. Here, we studied the induction of hippocampal long-term potentiation (LTP) while blocking group II mGluR2/3. Thirty-two male Wistar rats were assigned into four groups: a control group that consumed an ordinary diet; a HFD group that ate a HFD; "HFD plus LY341495" ate a HFD and later received a selective group II metabotropic glutamate receptor antagonist; and "Control plus LY341495" group. After 6 months on the specified diet, the rats were anesthetized with intraperitoneal injection of ketamine and xylazin, and placed in a stereotaxic apparatus for surgery, electrode implantation, and field potential recording. We microinjected LY341495 solution unilaterally into the dentate gyrus (DG) to block mGluR2/3. The population spike (PS) amplitude and slope of excitatory post synaptic potentials (EPSP) were measured in the DG area in response to stimulation applied to the perforant pathway (400 Hz tetanization). We found that, after tentanizing the perforant pathway to induce LTP, HFD decreased PS amplitude and slope of EPSP compared to controls. Moreover, blocking group II mGluRs increased LTP not only in controls, but also in rats fed on HFD. Therefore, our results show that LY341495 rescues hippocampal synaptic plasticity that can be impaired by a HFD. In summary, these results indicate that mGluR2/3 inhibition may have stimulatory effects on LTP induction in the DG.

Reciprocal Homosynaptic and heterosynaptic long-term plasticity of corticogeniculate projection neurons in layer VI of the mouse visual cortex.

Most neurons in layer VI of the visual cortex project to the dorsal lateral geniculate nucleus (dLGN). These corticogeniculate projection neurons (CG cells) receive top-down synaptic inputs from upper layers (ULs) and bottom-up inputs from the underlying white matter (WM). Use-dependent plasticity of these synapses in layer VI of the cortex has received less attention than in other layers. In the present study, we used a retrograde tracer injected into dLGN to identify CG cells, and, by analyzing EPSPs evoked by electrical stimulation of the UL or WM site, examined whether these synapses show long-term synaptic plasticity. Theta-burst stimulation induced long-term potentiation (LTP) of activated synapses (hom-LTP) and long-term depression (LTD) of nonactivated synapses (het-LTD) in either pathway. The paired-pulse stimulation protocol and the analysis of coefficient variation of EPSPs suggested postsynaptic induction of these changes except UL-induced het-LTD, which may be presynaptic in origin. Intracellular injection of a Ca(2+)-chelator suggested an involvement of postsynaptic Ca(2+) rise in all types of long-term plasticity. Pharmacological analysis indicated that NMDA receptors and type-5 metabotropic glutamate receptors are involved in WM-induced and UL-induced plasticity, respectively. Analysis with inhibitors and/or in transgenic mice suggested an involvement of cannabinoid type 1 receptors and calcineurin in UL-induced and WM-induced het-LTD, respectively. These results suggest that hom-LTP and het-LTD may play a role in switching the top-down or bottom-up regulation of CG cell function and/or in maintaining stability of synaptic transmission efficacy through different molecular mechanisms.

Effect of intrahippocampal microinjection of VU0155041, a positive allosteric modulator of mGluR4, on long term potentiation in a valproic acid-induced autistic male rat model.

The precise cause of autism spectrum disorder (ASD) is not fully understood. Despite the involvement of glutamatergic dysregulation in autism, the specific contribution of mGlu4 receptors to synaptic plasticity remains unclear. Using the positive allosteric modulator VU0155041, we aimed to restore long-term potentiation (LTP) in the perforant path-dentate gyrus (PP-DG) pathway in VPA-induced autistic rat model. High-frequency stimulation was applied to the PP-DG synapse to induce LTP, while the VU0155041 was administered into the DG. Unexpectedly, VU0155041 failed to alleviate the observed LTP reduction in VPA-exposed rats, further resulting in a significant decrease in population spike LTP. This unexpected outcome prompts discussion on the complex nature of mGlu4 receptor modulation, highlighting potential interference with physiological processes underlying synaptic plasticity.

Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in prenatal valproic acid-induced rat model of autism.

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition characterized by social interaction deficits, communication impairments, repetitive behaviors, and sensory sensitivities. While the etiology of ASD is multifaceted, abnormalities in glutamatergic neurotransmission and synaptic plasticity have been implicated. This study investigated the role of metabotropic glutamate receptor 8 (mGlu8) in modulating long-term potentiation (LTP) in a rat model of ASD induced by prenatal valproic acid (VPA) exposure. To induce an animal model with autism-like characteristics, pregnant rats received an intraperitoneal injection of 500 mg/kg of sodium valproate (NaVPA) on embryonic day 12.5. High-frequency stimulation was applied to the perforant path-dentate gyrus (PP-DG) synapse to induce LTP, while the mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG) was administered into the DG. The results revealed that VPA-exposed rats exhibited reduced LTP compared to controls. DCPG had contrasting effects, inhibiting LTP in controls and enhancing it in VPA-exposed rats. Moreover, reduced social novelty preference index (SNPI) in VPA-exposed rats was reversed by intra-DG administration of S-3,4-DCPG. In conclusion, our study advances our understanding of the complex relationship between glutamatergic neurotransmission, synaptic plasticity, and VPA-induced autism model. The findings suggest that mGlu8 receptor dysfunction plays a role in the impaired synaptic plasticity seen in ASD.

S-3,4-DCPG, a potent orthosteric agonist for the mGlu8 receptor, facilitates extinction and inhibits the reinstatement of morphine-induced conditioned place preference in male rats.

The limbic system, particularly the NAc, shows a high concentration of metabotropic glutamate receptors (mGluRs). Recent evidence suggests the significant involvement of mGluRs in mental disorders, including substance abuse and addiction. The objective of this study was to examine the involvement of mGlu8 receptors in the NAc in the mechanisms underlying the extinction and reinstatement of conditioned place preference (CPP) induced by morphine. Male Wistar rats underwent surgical implantation of bilateral cannulas in the NAc and were assessed in a CPP protocol. In study 1 at the same time as the extinction phase, the rats were given varying doses of S-3,4-DCPG (0.03, 0.3, and 3 µg/0.5 µl). In study 2, rats that had undergone CPP extinction were given S-3,4-DCPG (0.03, 0.3, and 3 µg/0.5 µl) five minutes prior to receiving a subthreshold dose of morphine (1 mg/kg) in order to reactivate the previously extinguished morphine response. The findings demonstrated that administering S-3,4-DCPG directly into the accumbens nucleus resulted in a decrease in the duration of the CPP extinction phase. Moreover, dose-dependent administration of S-3,4-DCPG into the NAc inhibited CPP reinstatement. The observations imply that microinjection of S-3,4-DCPG as a potent orthosteric agonist with high selectivity for the mGlu8 receptor into the NAc promotes the process of extinction while concurrently exerting inhibitory effects on the reinstatement of morphine-induced CPP. This effect may be associated with the modulation of glutamate engagement within the NAc and the plasticity of reward pathways at the synaptic level.

Uncovering the protective potential of vanillic acid against traumatic brain injury-induced cognitive decline in male rats: Insights into underlying mechanisms.

Traumatic brain injury (TBI) is a significant contributor to global mortality and disability, and there is still no specific drug available to treat cognitive deficits in survivors. Vanillic acid (VA), a bioactive phenolic compound, has shown protective effects in various models of neurodegeneration; however, its impact on TBI outcomes remains elusive. Therefore, this study aimed to elucidate the possible role of VA in ameliorating TBI-induced cognitive decline and to reveal the mechanisms involved. TBI was induced using the Marmarou impact acceleration model to deliver an impact force of 300 g, and treatment with VA (50 mg/kg; P.O.) was initiated 30 minutes post-TBI. The cognitive performance, hippocampal long-term potentiation (LTP), oxidative stress markers, neurological function, cerebral edema, and morphological changes were assessed at scheduled points in time. TBI resulted in cognitive decline in the passive avoidance task, impaired LTP in the perforant path-dentate gyrus (PP-DG) pathway, increased hippocampal oxidative stress, cerebral edema, neurological deficits, and neuronal loss in the rat hippocampus. In contrast, acute VA administration mitigated all the aforementioned TBI outcomes. The data suggest that reducing synaptic plasticity impairment, regulating oxidative and antioxidant defense, alleviating cerebral edema, and preventing neuronal loss by VA can be at least partially attributed to its protection against TBI-induced cognitive decline.

Cell type-specific, presynaptic LTP of inhibitory synapses on fast-spiking GABAergic neurons in the mouse visual cortex.

Properties and plasticity of inhibitory synapses on fast-spiking (FS) GABAergic (FS-GABA) interneurons in layer II/III of the mouse visual cortex were examined in cortical slices by whole-cell recordings of IPSCs or IPSPs evoked by activation of presynaptic FS or non-FS GABAergic interneurons. Unitary IPSCs (uIPSCs) evoked by action potentials of FS-GABA neurons have shorter onset latency, faster rising slope, higher peak amplitude, and faster decay time than those evoked by action potentials of non-FS-GABA neurons. Tetanic activation of presynaptic FS-GABA neurons induced long-term potentiation (LTP) of uIPSCs, whereas that of presynaptic non-FS-GABA neurons did not induce LTP, indicating that long-term plasticity of inhibitory synapses on FS-GABA neurons is pathway specific. For further analysis of inhibitory synaptic plasticity, IPSPs evoked by electrical stimulation of an adjacent site in the cortex were recorded from FS-GABA neurons. Theta burst stimulation induced LTP of IPSPs in 12 of 14 FS-GABA neurons. The paired-pulse stimulation protocol and coefficient of variation analysis indicated that this form of LTP may be presynaptic in origin. Filling postsynaptic cells with a Ca(2+) chelator did not block the induction of LTP, suggesting no involvement of postsynaptic Ca(2+) rise. Also, this form of LTP was dependent neither on metabotropic glutamate receptors nor voltage-gated Ca(2+) channels of the L and T types. Further pharmacological analysis indicated that voltage-gated Ca(2+) channels other than the P/Q type, such as N and R types, were not involved in LTP, suggesting that P/Q-type channels are a candidate for factors inducing LTP of inhibitory synapses between FS-GABA neurons.

Effect of Elettaria cardamomum L. on hormonal changes and spermatogenesis in the propylthiouracil-induced hypothyroidism male BALB/c mice.

INTRODUCTION: Spermatogenesis is significantly influenced by the thyroid gland. Thyroid disorders can be caused by a variety of factors. Traditionally, Ellettaria cardamomum has been used to treat a variety of ailments. The effects of E. cardamomum extract (ECE) on spermatogenesis in hypothyroid mice were investigated in this study. METHODS: In this study 42 male mice, weighing (25-35 g) were randomly divided in six groups: control group (taking normal saline, 0.5 mL/day, by oral gavage [P.O.]), hypothyroid group (taking 0.1% propylthiouracil in drinking water for 2 weeks), hypothyroid groups treated by levothyroxine (15 mg/kg/day, P.O.) and hypothyroid groups treated by ECE (100, 200 and 400 mg/kg/day, P.O.). After the end of experiments the mice were anaesthetised and blood samples were collected for hormonal analysis. RESULTS: The sperm count and microscopic studies of testes were done also. Our results showed that the T3 , T4 , testosterone levels and spermatogenesis in hypothyroid animals decreased and thyroid-stimulating hormone, follicle-stimulating hormone and luteinizing hormone increased compared with control group. Treatment by ECE reverse these effects in comparison with hypothyroid group. CONCLUSIONS: According to our findings, the ECE may stimulates thyroid gland function and increases testosterone and spermatogenesis.

In silico molecular modeling, neuro-behavioral profile, and toxicity assessment of the essential oil of Ferula gummosa Boiss. as an anti-seizure agent.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferula gummosa Boiss., known in Persian as "Baridje," belongs to the Apiaceae family. All parts of this plant, especially the root, contain galbanum. Galbanum, the oleo-gum resin of F. gummosa, is one of the essential traditional herbal medicines in Iran, which is used as a tonic for epilepsy and chorea, memory enhancement, gastrointestinal diseases, and wound healing. AIM OF THE STUDY: We investigated the toxicity, anticonvulsant effects, and molecular modeling of the essential oil (EO) distilled from the oleo-gum resin of F. gummosa. MATERIALS AND METHODS: Gas chromatography-mass spectrometry was used to identify the EO components. The cytotoxicity of EO on HepG2 cell lines was assessed by the MTT method. Male mice were arranged as follows: negative control groups (sunflower oil (10 ml/kg, i.p.) or saline (10 ml/kg, p.o.)), EO groups (0.5, 1, 1.5, and 2.5 ml/kg, p.o.), and positive control groups (ethosuximide (150 mg/kg, p.o.) or diazepam (1.0 or 2 mg/kg, i.p.)). The motor coordination and neurotoxicity of EO were studied using the rota-rod test. Open-field, novel object recognition, and passive avoidance learning tests were used to investigate the effect of EO on locomotor activity and memory function. An acute pentylenetetrazole-induced seizure model was utilized to evaluate the anticonvulsant properties of the EO. The interaction of the EO main components with the GABAA receptor was investigated by coarse-grained molecular dynamics simulations. RESULTS: ß-pinene, sabinene, α-pinene, and ρ-cymene were the main components of EO. The IC50 of the EO at 24, 48, and 72 h was found to be 59.90, 12.96, and 3.93 µl/ml, respectively. No adverse effects were observed in memory, motor coordination, and locomotor activity in mice treated with EO. Administration of EO (1, 1.5, and 2.5 ml/kg) improved survival rates in mice receiving pentylenetetrazole (PTZ; to induce an epileptic seizure). Sabinene was able to bind to the binding site of benzodiazepines at the GABAA receptor. CONCLUSIONS: Acute treatment with the EO of F. gummosa caused antiepileptic effects and could effectively increase the survival rate in PTZ-treated mice with no significant toxicity.