GABA Levels Research Articles

The Study of the Influence of Pyridine Oxime Derivative (GIZh-298) And Sodium Valproate on the Neurotransmitter Amino Acids Content in the Brain Structures of Mice in the Maximal Electroconvulsive Seizures Test

The effect of the antiepileptic compound GIZH-298 and the reference drug sodium valproate (VN) on the content of excitatory and inhibitory amino acids in the frontal cortex, hypothalamus, striatum, and hippocampus of the brain of mice after an electric shock-induced generalized tonic-clonic seizure (MES) was studied. It has been shown that the application of MES reduces the levels of aspartate, glycine, GABA and the ratio of “GABA/glutamate” in the hypothalamus. In the latter, a decrease in the concentration of glutamate, glycine and taurine was noted. VN (200 mg/kg/g) counteracts the effects of MES by interfering with the resulting decrease in GABA and the GABA/glutamate ratio in the hypothalamus. In the hypothalamus, striatum, and hippocampus, VN causes a decrease in the aspartate content both in intact control groups and in the group of mice that received MES. GIZH-298 (60 mg/kg/int. gastric) prevented the MES-induced decrease in the levels of GABA, glycine and taurine and the GABA/glutamate ratio in the hypothalamus.

Features оf Changes in the Level of Neurotransmitters and Markers of Neurodegeneration in the Brain of Rats with Experimental Parkinson’s Disease Against the Background of Course Therapy with Steroid Glycoalkaloids

Parkinson’s disease is a chronic neurodegenerative disease, one of the pathobiochemical manifestations of which is an imbalance of neurotransmitters in the brain. The aim of this work is to study the effect of glycoalkaloids on changes in the level of neurotransmitters and markers of brain neurodegeneration in rats with experimental Parkinson’s disease. Parkinson’s disease was modeled in animals by intracerebral administration of rotenone. The studied glycoalkaloids were administered orally at a dose of 0.06 mg / kg, a course of 28 days after pathology modeling. The study found that the use of the analyzed glycoalkaloids did not affect the concentration of dopamine and serotonin, and also significantly (p 0.05) reduced the level of ACh by 35.9% and increased the level of GABA by 55.1%, reduced the concentration of S100β protein by 68.6% and increased the level of BDNF by 52.4%.

Potential Disease-Modifying Effects of Ganglioside GM1 Pulse Treatment on Spinocerebellar Ataxia Type 3, a Parallel-Group, Double-Blind, Randomized, Controlled Trial.

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited neurodegenerative disorder for which there is currently no cure, nor effective treatment strategy. Our aim was to investigate the safety and efficacy of high-dose ganglioside GM1 (ganglioside-monosialic acid) pulse treatment in patients with SCA3. Patients were randomly allocated to receive either high-dose GM1 (400 mg on the first day followed by 200 mg/day), low-dose GM1 (40 mg/day), or placebo (normal saline) for 4 weeks. The primary outcome, assessed by measuring the change in the Scale for the Assessment and Rating of Ataxia (SARA) scores from baseline to 12 weeks post-treatment, is central to evaluating treatment efficacy. Secondary outcomesincluded changes in the International Cooperative Ataxia Rating Scale (ICARS) score, Barthel Index of Activities of Daily Living (ADL), and plasma and cerebrospinal fluid (CSF) GABA levels. Safety was assessed in all treated patients. A total of 48 patients with SCA3 were enrolled in this study. After 12 weeks, data from 43 patients were included in the efficacy analysis (intention-to-treat analysis). The least-squares mean change in the SARA score from baseline to 12 weeks post-treatment was -3.80 (standard error [SE], 0.39; 95% confidence interval [CI], -4.58 to -3.02) in the high-dose GM1 group, 0.34 (SE, 0.40; 95% CI, -0.46 to 1.13) in the low-dose GM1 group, and 0.73 (SE, 0.40; 95% CI, -0.07 to 1.52) in the placebo group, respectively. Secondary outcomes showed improvements in the ICARS score, Barthel Index of ADL, and plasma and CSF GABA levels in the high-dose GM1 group compared to the low-dose GM1 and placebo groups. All treatments were well-tolerated and safe. High-dose GM1 treatment significantly ameliorated ataxic symptoms in patients with SCA3. © 2024 International Parkinson and Movement Disorder Society.

Rebalance the Inhibitory System in the Elderly Brain: Influence of Balance Learning on GABAergic Inhibition and Functional Connectivity.

Aging involves complex processes that impact the structure, function, and metabolism of the human brain. Declines in both structural and functional integrity along with reduced local inhibitory tone in the motor areas, as indicated by reduced γ-aminobutyric acid (GABA) levels, are often associated with compromised motor performance in elderly adults. Using multimodal neuroimaging techniques including magnetic resonance spectroscopy (MRS), diffusion magnetic resonance imaging (MRI), functional MRI as well as transcranial magnetic stimulation to assess short-interval intracortical inhibition (SICI), this study explores whether these age-related changes can be mitigated by motor learning. The investigation focused on the effects of long-term balance learning (3 months) on intracortical inhibition, metabolism, structural, and functional connectivity in the cortical sensorimotor network among an elderly cohort. We found that after 3 months of balance learning, subjects significantly improved balance performance, upregulated sensorimotor cortical GABA levels and ventral sensorimotor network functional connectivity (VSN-FC) compared to a passive control group. Furthermore, correlation analysis suggested a positive association between baseline VSN-FC and balance performance, between baseline VSN-FC and SICI, and between improvements in balance performance and upregulation in SICI in the training group, though these correlations did not survive the false discovery rate correction. These findings demonstrate that balance learning has the potential to counteract aging-related decline in functional connectivity and cortical inhibition on the "tonic" (MRS) and "functional" (SICI) level and shed new light on the close interplay between the GABAergic system, functional connectivity, and behavior.

γ-Aminobutyric Acid Alleviates Salinity-Induced Impairments in Rice Plants by Improving Photosynthesis and Upregulating Osmoprotectants and Antioxidants

Salt stress is a significant abiotic stress that hinders the growth of rice (Oryza sativa L.) and reduces their yield. Previous research has examined the synthesis of γ-aminobutyric acid (GABA) and its role in plant resistance under various abiotic stresses. However, the synthesis of GABA and its ability to mitigate damage caused by salt stress—particularly its effects on osmotic adjustment, antioxidant defense, photosynthesis, and overall plant growth throughout the entire rice lifecycle—remains unclear. Therefore, we conducted two experiments using salt-tolerant rice cultivar Lianjian 5 (J-5) and salt-susceptible cultivar Lianjing 7 (L-7). In Experiment I, RNA-seq (RNA sequencing) was used to analyze the differential expression of the transcriptome between CK and salinity treatments, revealing the key roles of GABA in salt tolerance. In Experiment II, different levels of exogenous GABA were applied to salt-stressed plants to investigate its physiological role in enhancing salt tolerance. Therefore, RNA-seq (RNA sequencing) was used to analyze the differential expression of the transcriptome between CK and salinity treatments, revealing the key roles of GABA in salt tolerance. Subsequently, different levels of exogenous GABA were applied to salt-stressed plants to investigate its physiological role in enhancing salt tolerance. We measured the activities of superoxide dismutase, peroxidase, and catalase, as well as photosynthetic characteristics such as photosynthesis, transpiration, chlorophyll content, stomatal density and size, and leaf anatomical features. The RNA-seq analysis revealed that GABA production is enhanced via the glutamate decarboxylase (GAD) gene (LOC4333932) in the salt-resistant rice cultivar. Exogenous GABA application improves salt-stress tolerance by increasing endogenous ABA and GABA contents, which enhance osmotic adjustment, boost antioxidant defenses, and regulate ion balance. These combined effects help maintain photosynthetic efficiency and support overall plant growth under salt-stressed environments. Additionally, the increased proportion of mesophyll cell periphery covered by chloroplasts (Sc/Sm) indicated enhanced mesophyll conductance. These helped maintain photosynthesis under saline conditions while reducing water consumption.

Optimization of Germination Conditions for Enriched γ-Aminobutyric Acid and Phenolic Compounds of Foxtail Millet Sprouts by Response Surface Methodology.

The optimum germination conditions for foxtail millet sprouts enriched with γ-aminobutyric acid (GABA) and antioxidant polyphenols were investigated. From single-factor experimental results, both the GABA level and total phenolic content (TPC) were more significantly affected by soaking temperature and time, and concentration of sucrose culture solution. Response surface methodology (RSE) was used to optimize the germination conditions of foxtail millet sprouts, where the interaction between soaking temperature and sucrose concentration exhibited a significant (p < 0.05) effect on TPC, and the interaction between soaking time and sucrose concentration displayed a significant (p < 0.05) effect on GABA content. The optimal germination conditions for TPC and GABA enrichment of foxtail millet sprouts were soaking at 31 °C for 4.5 h and germinating at 35 °C with 4.5 g/L sucrose solution for 5 days. Under the optimized conditions, the TPC and GABA content of foxtail millet sprouts were 926.53 milligrams of ferulic acid equivalents per 100 g dry weight (mg FAE/100 g DW) and 259.13 mg/kg, separately, with less difference from the predicted values of 929.44 mg FAE/100 g DW and 263.60 mg/kg, respectively. Collectively, all the individual phenolic compounds increased significantly (p < 0.05) by optimization, except for cis-p-coumaric acid and cis-ferulic acid in bound. The results provide a practical technology for suitable germination conditions to improve the health components of foxtail millet sprouts and increase their added value.

A Review on Phytochemical Constituents Used as Current Treatment Strategies for Neurodegenerative Disease.

In today's time, a diversity of neurodegenerative diseases that widely affect the CNS causing insufficiency in particular brain processes such as memory, mobility, and cognition due to the moderate loss of CNS neurons. This review emphasizes different phytochemical constituents used widely for the prevention or treatment of various neurodegenerative diseases such as Alzheimer's disease (AD) and Parkin-son's disease (PD). Berberin (BBR), which is an isoquinoline class of alkaloid and isolated from the plant Hydrastis condenses and Berberis aaristata, has both acetylcholine esterase (AChE) inhibiting properties as well as monoamine oxidase (MAO) inhibiting properties involved in the betterment of AD by decreasing the production of reactive oxygen species (ROS). Like BBR, Physostigmine, isolated from the Physostigma venenosum / Calabar bean and belongs to the family Leguminosae, and Morphine, isolated from the plant Papaver somniferum / Opium poppy or Breadseed poppy, also has a significant impact on the management and treatment of AD and PD by reducing both neuroinflammation and pro-inflammatory cytokines production. Morphine bineurodegenerative diseases with μ-opioid receptor (MOR) in CNS elevate GABA levels in the synaptic cleft of the brain and reduces the neurotoxicity via stimulation of MOR. It has been discovered that physostigmine improves cognitive function in AD patients and reduces α-synu-clein expression in PD neural cell lines. Isorhyncophylline (IRN) is a Chinese herbal medicine isolated from the plant Uncaria rhyncophylla which provides neuroprotective efficiency against neurotoxicity that occurs by amyloid β (the main component of amyloid plaques) found in the brain of people with AD.

Reduced GABA Levels in the ACC of Actively Drinking High Risk Individuals Compared to Recently Detoxified Alcohol-Dependent Patients.

Acute gamma-aminobutyric acid (GABAergic) effects of alcohol consumption are well-known, whereas prior research has yielded inconsistent findings regarding on adaptations of the GABAergic neurotransmitter system to chronic alcohol use. Previous studies indicate either elevated or reduced GABA levels in cortical regions such as the anterior cingulate cortex (ACC) in persons with alcohol use disorder (AUD). We tested the hypothesis that active alcohol consumption compared to abstinence contributes to GABA levels as observed in prior research on chronic alcohol use. We investigated GABA levels in the ACC of 31 healthy controls (low risk, LR), 38 high risk individuals providing an active drinking pattern (high risk, HR) and 27 recently detoxified alcohol-dependent (AD) subjects via proton magnetic resonance spectroscopy (1H-MRS). GABA levels in the ACC were significantly lower in HR compared with AD, but did neither differ between LR and AD nor between LR and HR. Also, we observed a quadratic effect indicating a distribution of GABA levels in the ACC as follows: LR > HR < AD. GABA levels were not associated with abstinence duration in AD. This study suggests that the GABAergic neurotransmitter system is blunted in AUD. More precisely GABA levels in the ACC seem to be higher in recently detoxified AD patients than in individuals at high risk which might suggest that GABA levels may increase after abstinence. No correlation was found between GABA levels and abstinence duration. Longitudinal studies are required to investigate alterations in the GABAergic system throughout the development and maintenance of AUD. No: NCT02094196. Registered 20 March 2014, https://clinicaltrials.gov/study/NCT02094196.

Synergistic effects of peripheral GABA and GABA-transaminase inhibitory drugs on food intake control and weight loss in high-fat diet-induced obese mice.

Developing anti-obesity interventions targeting appetite or food intake, the primary driver of obesity, remains challenging. Here, we demonstrated that dietary γ-aminobutyric acid (GABA) with GABA-degradation inhibitory drugs could be an anti-obesity intervention possessing strong food intake-suppressive and weight-loss effects. High-fat (HF)-diet-induced obese mice were divided into six groups receiving either the HF diet or the 2% GABA-HF diet with daily administration of PBS or the GABA-degradation inhibitory drugs, vigabatrin and ethanolamine-O-sulfate (EOS). In 24-h fast-induced refeeding, lean mice with a basal diet were used, and food intake was measured from 0.5 to 24h after refeeding. Coadministration of the 2% GABA-HF diet with vigabatrin or EOS significantly decreased food intake (-53%, -35%) and body weight (-22%, -16%) within 11days in obese mice, along with a marked increase in plasma GABA levels. Mice receiving dietary GABA alone or the drugs alone exhibited no such effects. Hypothalamic GABA levels increased in drug-treated mice, regardless of diet. At 0.5h after refeeding, food intake was similar in all groups. However, at 0.5h, plasma GABA levels were markedly increased only in mice receiving coadministration of dietary GABA and the drugs, and their food intake was completely inhibited for over 6h, while mice in other groups gradually increased their food intake. Combining dietary GABA with GABA-degradation inhibitory drugs effectively suppresses food intake and promotes weight loss in obese mice, primarily through increased plasma GABA availability. These findings may advance the development of food intake-controlling strategies for obesity management.

Impact of levetiracetam and ethanol on memory, selected neurotransmitter levels, oxidative stress parameters, and essential elements in rats.

Ethanol disrupts brain activity and memory. There is evidence supporting the beneficial effect of levetiracetam on alcohol consumption. Therefore, the aim of the study was to examine whether levetiracetam has a protective activity against ethanol-induced memory impairment, alterations in selected neurotransmission activities, oxidative stress, and selected essential elements in rats. The rats were given levetiracetam (300mg/kg b.w. po) with ethanol for three weeks prior to behavioral tests. Spatial memory was tested using the Morris water maze, while recognition memory was evaluated using the Novel object recognition test. The GABA and glutamate concentration was determined in three rat brain regions (cerebellum, hippocampus, and cerebral cortex). Serum oxidative stress parameters and selected essential elements concentration (Cu, Mn, Zn, Fe, Mg) in the rat brain were analyzed. Levetiracetam administered with ethanol improved spatial memory, but did not affect abstinence-induced impairment. The drug also decreased ethanol-induced long-term recognition memory impairment. No alterations in glutamate levels were observed. GABA levels were elevated by levetiracetam in the cerebral cortex and by ethanol in the cerebellum. Ethanol increased catalase activity (CAT) and decreased superoxide dismutase activity (SOD) in the serum. Levetiracetam significantly increased the activity of SOD. Alcohol disrupted the levels of trace elements (Mn, Zn, Mg) in the rat brain. Additionally, levetiracetam alone increased Mg, Fe, and Cu concentrations while all animals receiving the drug also had significantly lower concentrations of Zn. Levetiracetam had differential effects against ethanol-induced impairments. These findings could have important implications for future levetiracetam treatment in patients.

CsGAT1 modulates GABA metabolism and positively regulates cold resistance in tea plants

Tea plants (Camellia sinensis) are perennial woody economic crops that are often exposed to a range of abiotic stresses, especially low temperatures, during development. γ-Aminobutyric acid (GABA) is a nonprotein amino acid widely distributed in plants that is involved in the low-temperature response of plants. Here, we found that CsGAT1 was upregulated in tea leaves subjected to low-temperature stress according to transcriptomic data. Heterologous expression of CsGAT1 in a yeast mutant revealed that it specifically transports GABA. Subcellular localization assays revealed that CsGAT1 was located on the plasma membrane. The organizational localization experiments revealed that the expression level of CsGAT1 was relatively high in the old leaves and roots and relatively low in the flowers. Testing of different cold-tolerant tea germplasm resources revealed that cultivars with relatively low cold resistance presented relatively low CsGAT1 expression and GABA levels. In addition, Arabidopsis plants overexpressing CsGAT1 presented high levels of GABA accumulation and significant low-temperature resistance. In summary, we believe that CsGAT1 regulates the ability of tea plants to resist low-temperature stress by changing the concentration of GABA inside and outside the cell. This study provides a theoretical basis for breeding new tea cultivars with strong resistance to low-temperature stress during production.

Sub-acute Inhalation Exposure to Aluminum Oxide Nanoparticles and its Effects on Wistar Rats as Opposed to the Micro-sized Chemical Analog.

Aluminum oxide nanoparticles (Al2O3 NPs) are widely used in various productions. Simultaneously, many research works report the toxic effects of this nanomaterial. Given that, there is a growing risk of negative effects produced by Al2O3 NPs on public health. This study aims to investigate the toxic effects of Al2O3 NPs as opposed to the micro-sized chemical analogue under sub-acute inhalation exposure. We identified the physical properties of Al2O3 NPs as opposed to the micro- sized chemical analogue, including size, specific surface area, and total pore volume. Inhalation exposure to Al2O3 NPs was simulated on Wistar rats in a chamber for whole-body. The animals were exposed for 4 hours each day for 28 days. NPs and MPs concentrations in the chamber were kept at ~ 1/4000 from LC50. Rats' behavior was examined prior to the exposure period and after it; after the last daily exposure, we examined biochemical and hematological blood indicators, NPs and MPs bioaccumulation, and pathomorphological changes in organ tissues. The tested Al2O3 sample is a nanomaterial according to its analyzed physical properties. Rats' behavior changed more apparently under exposure to NPs compared to MPs. Aluminum levels, which were 1.62-55.20 times higher than the control, were identified in the lungs, liver, brain, and blood under exposure to NPs. These levels were also 1.55-7.65 times higher than the control under exposure to MPs. Biochemical indicators of rats' blood also changed under exposure to NPs against the control. We identified more active ALT, AST, ALP, and LDH, elevated levels of GABA, MDA, and conjugated bilirubin, and a lower level of Glu. As opposed to exposure to MPs, ALT, AST, and ALP were more active; GABA and MDA levels were higher; Glu level was lower. Under exposure to NPs, the number of platelets grew, whereas no similar effect occurred under exposure to MPs. We established pathomorphological changes in tissues of the lungs, brain, heart, and liver under exposure to Al2O3 NPs; similar changes occurred only in the lungs under exposure to MPs. Exposure to NPs induced changes in tissue structures in a wider range of various organs, and these changes were more apparent than under exposure to MPs. Greater toxicity of Al2O3 NPs as opposed to MPs is evidenced by a wider range of organs where their bioaccumulation occurs, more apparent pathomorphological and pathological functional changes. Established peculiarities of toxic effects produced by the analyzed nanomaterial should be considered when developing hygienic recommendations aimed at preventing and mitigating adverse impacts of Al2O3 NPs on human health under inhalation exposure.

Unpredictable chronic mild stress induced anxio-depressive disorders and enterobacteria dysbiosis: Potential protective effects of Detariummicrocarpum

Ethnopharmacological relevanceDetarium microcarpum Guill. & Perr. is used traditionally in Far North Cameroun to treat stomach aches, anxiety, epilepsy, and other mental disorders. Aim of the studyEvaluate the anxiolytic and antidepressant-like effects of D. microcarpum (DM) in unpredictable chronic mild stress (UCMS) model of depression in male rats and its impact on fecal enterobacteria of stressed rats. Materials and methodsRats were handled daily (control) or subjected to the UCMS procedure for 42 days. Anxiety-like behaviors were assessed using the light and dark box test (LBD) and the open field test (OFT). Depressive-like behaviors were assessed using the forced swimming test (FST), the sucrose preference test (SPT), and the novelty suppressed feeding test (NSFT). Feces were then collected, followed by blood, brain, and duodenum sections after sacrifice. Monoamine levels, pro-inflammatory cytokines, oxidative stress factors, and nitrosative stress were assessed. Feces were introduced into Hectoen enteric agar for the identification of enterobacteria. An in vitro growth test was performed. ResultsThe DM ethanolic extract has significantly increased the time spent in the light box, in the LBD, and in the center area of the OFT. Moreover, the extract has significantly reduced the preference for sucrose in the SPT, the time of immobility in the FST, and the latency period to consume the pet in the NSFT. DM extract has significantly reduced serum cortisol levels. It also significantly decreased the pro-inflammatory cytokines TNF-α and Il-1β in both brain and duodenum homogenate. DM has increased the brain's serotonin, GABA, and dopamine levels. The DM extract also decreased the MDA and nitrite levels. It also increased the SOD and CAT activities in both brain and duodenal homogenate. Histologically, the DM extract restored the cell's density in hippocampi sections and prevented gut inflammation and peroxidation characterizing leaky gut syndrome. DM extract has no effect on the growth of enterobacteria species isolated in vitro. ConclusionThe ethanolic extract of DM would have anxiolytic and antidepressant effects via the modulation of the HPA axis, brain antioxidant enzyme activities, inflammation, and nitrosative stress. Moreover, it could act by preventing leaky gut syndrome.

Ethanolic and aqueous extracts of Lantana camara show antiepileptic and anxiolytic effects by inhibiting the ferroptosis pathway in kainate-treated mice

In Cameroon, epilepsy is one of the most common neurological diseases. Available anti-epileptic medication, on the other hand, have been associated with pharmacological toxicity and emotional impairment. The identification of a more efficient replacement is critical. Recent research reveals that ferroptosis contributes to the pathophysiology of epilepsy and related anxiety disorders. Lantana camara is a plant with a high neuropharmacological potential, but its mechanisms of action have yet to be understood. The purpose of this study was to determine the effect of ethanolic and aqueous extracts of Lantana camara on the kainate model of epilepsy in mice. The focus was on these extracts' capacity to suppress ferroptosis. Mice were injected with kainate (12 mg/kg, i.p.) to induce epilepsy. After status epilepticus, animals were left for 19 days, which correspond to an epileptogenic period. After the appearance of spontaneous recurrent seizures, mice were treated with distilled water (10 ml/kg, p.o.), levetiracetam (80 mg/kg, p.o.), sodium valproate (300 mg/kg, p.o.), ethanolic extract of L. camara (230, 460, 920 mg/kg, p.o.), or an aqueous extract of L. camara (460 mg/kg p.o.). These treatments lasted for 14 days. During this period, the number and duration of seizures were recorded. The mice were then subjected to elevated zero-maze and open field tests to assess anxiety-like behavior. At the end, mice were sacrificed and hippocampus, amygdala, and striatum were dissected out for biochemical and histological analyses. The extracts alleviated seizure- and anxiety-like behavior in KA-treated mice. Decreased iron levels, reflected by a decrease in ferritin levels and a increase in transferrin levels, were observed in the hippocampus, striatum and amygdala of the extract-treated group compared to the KA-treated group. In addition, increase in GABA and GSH levels, and a decrease in MDA levels were observed in these groups. Hematoxylin-eosin staining revealed less pronounced neuronal degeneration and a more sustained architecture in the brain region of extract-treated mice. These findings indicated that ethanolic and aqueous extracts of L. camara effectively attenuate seizures and anxiety disorders. Probable mechanisms of action include GABAergic, iron, GSH, and MDA modulations.

Inhibitory mechanisms in the prefrontal-cortex differentially mediate Putamen activity during valence-based learning.

Learning from appetitive and aversive stimuli involves interactions between the prefrontal cortex and subcortical structures. Preclinical and theoretical studies indicate that inhibition is essential in regulating the relevant neural circuitry. Here, we demonstrate that GABA, the main inhibitory neurotransmitter in the central nervous system, differentially affects how the dACC interacts with subcortical structures during appetitive and aversive learning in humans. Participants engaged in tasks involving appetitive and aversive learning, while using functional magnetic resonance spectroscopy (MRS) at 7T to track GABA concentrations in the dACC, alongside whole-brain fMRI scans to assess BOLD activation. During appetitive learning, dACC GABA concentrations were negatively correlated with learning performance and BOLD activity measured from the dACC and the Putamen. These correlations were absent during aversive learning, where dACC GABA concentrations negatively correlated with the connectivity between the dACC and the Putamen. Our results show that inhibition in the dACC mediates appetitive and aversive learning in humans through distinct mechanisms.

Salicylic Acid and Melatonin Synergy Enhances Boron Toxicity Tolerance via AsA-GSH Cycle and Glyoxalase System Regulation in Fragrant Rice.

Background: Boron is an essential micronutrient for plant growth and productivity, yet excessive boron leads to toxicity, posing significant challenges for agriculture. Fragrant rice is popular among consumers, but the impact of boron toxicity on qualitative traits of fragrant rice, especially aroma, remains largely unexplored. The individual potentials of melatonin and salicylic acid in reducing boron toxicity are less known, while their synergistic effects and mechanisms in fragrant rice remain unclear. Methods: Thus, this study investigates the combined application of melatonin and salicylic acid on fragrant rice affected by boron toxicity. One-week-old seedlings were subjected to boron (0 and 800 µM) and then treated with melatonin and salicylic acid (0 and 100 µM, for 3 weeks). Results: Boron toxicity significantly impaired photosynthetic pigments, plant growth, and chloroplast integrity while increasing oxidative stress markers such as hydrogen peroxide, malondialdehyde, methylglyoxal, and betaine aldehyde dehydrogenase. Likewise, boron toxicity abridged the precursors involved in the 2-acetyl-1-pyrroline (2-AP) biosynthesis pathway. However, individual as well as combined application of melatonin and salicylic acid ameliorated boron toxicity by strengthening the antioxidant defense mechanisms-including the enzymes involved during the ascorbate-glutathione (AsA-GSH) cycle and glyoxalase system-and substantially improved 2-AP precursors including proline, P5C, Δ1-pyrroline, and GABA levels, thereby restoring the 2-AP content and aroma. These findings deduce that melatonin and salicylic acid synergistically alleviate boron toxicity-induced disruptions on the 2-AP biosynthesis pathway by improving the 2-AP precursors and enzymatic activities, as well as modulating the physio-biochemical processes and antioxidant defense system of fragrant rice plants. Conclusions: The findings of this study have the potential to enhance rice productivity and stress tolerance, offering solutions to improve food security and sustainability in agricultural practices, particularly in regions affected by environmental stressors.

Aphrodisiac activity of aqueous extract of Anthonotha macrophylla (P. Beauv) leaves in paroxetine-induced sexual dysfunction male Wistar rats

Ethno-pharmacological relevanceAnthonotha macrophylla, a plant with extensive ethnomedicinal uses, has various parts attributed to healing properties. The bark is claimed to be used to treat venereal diseases while the roots are used to treat intestinal discomfort. Gum extract from the bark provides pain relief, while the leaves are used for treating gonorrhoea, diarrhoea, and malaria. Additionally, the leaves are believed to enhance sexual behaviour. Although the age-long folkloric use of Anthonotha macrophylla leaf as aphrodisiac in female rats was substantiated with scientific evidence, the study did not account for the aphrodisiac activity in paroxetine-induced sexual dysfunction in male rat model. Aim of the studyThis study investigated the aphrodisiac activity of aqueous extract of Anthonotha macrophylla leaves (AEAML) in paroxetine-induced sexual dysfunction male rats (PISDMR). Materials and methodsForty-two male rats (144.86 ± 1.21 g) were assigned into six groups (A-F). Group A received distilled water only, while PISDMR in Groups B, C, D, E and F received distilled water, 7.14 mg/kg body weight of sildenafil citrate (reference drug), 25, 50 and 100 mg/kg body weight of AEAML once daily for 7 days. Data were analyzed using a one-way Analysis of Variance (ANOVA) and Tukey's post-hoc test at a 5% level of significance after the determination of male sexual behaviour parameters and associated biochemical indices. ResultsAEAML contained 8 mineral elements and 14 amino acids; potassium (368.24 mg/100g) and glycine (352.70 mg/100g) were the most abundant while cadmium (0.01 mg/100g) and histidine (0.70 mg/100g) were the least. Administration of paroxetine prolonged/increased (p < 0.05) the mount latency (ML), intromission latency (IL), ejaculation latency (EL), post-ejaculatory interval (PEI), and lowered/reduced (p < 0.05) the mount frequency (MF), intromission frequency (IF) and ejaculation frequency (EF). Paroxetine also decreased the weight of the caudal epididymis, seminal vesicle, ventral prostate, and testis, levels of dihydrotestosterone (DHT), testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), dopamine, acetylcholine (ACH), nitric oxide (NO), cyclic guanosine monophosphate (cGMP) and increased the levels of serotonin, γ-aminobutyric acid (GABA), phosphodiesterase V (PDE V) and acetylcholinesterase (AChE) of the animals. In contrast, AEAML significantly (p < 0.05) lowered/reduced the paroxetine-induced related increases in the ML, IL, EL, PEI, and prolonged/increased (p < 0.05) the paroxetine-induced related decreases in the MF, IF and EF. The AEAML also reversed (p < 0.05) the paroxetine-induced related decreases in the weight of the caudal epididymis, seminal vesicle, ventral prostate, testis, levels of DHT, testosterone, LH, FSH, dopamine, ACH, NO, cGMP and the paroxetine-induced related increases in the levels of serotonin, GABA, PDE V and AChE. ConclusionAEAML contains aphrodisiac bioactive agents that can be explored as drug lead for MSD.

Comparative Evaluation of Chemical Compositions and Antioxidant Activity in Fruiting Bodies and Mycelia of Volvariella volvacea and Pleurotus sajor-caju Extracts.

Mushrooms, recognized for their rich medicinal and nutritional content, have garnered significant interest due to their potent antioxidant properties. This study investigates the fruiting bodies and mycelia of straw mushrooms (Volvariella volvacea) and grey oyster mushrooms (Pleurotus sajor-caju). The mushrooms were extracted using distilled water at ratios of 1:25, 1:30, and 1:35 g/mL by soaking in a temperature-regulated shaking bath set at 50°C. The aqueous extracts were analyzed for their bioactive components, including polysaccharides, proteins, GABA, total phenolic content (TPC), and total flavonoid content (TFC), along with their antioxidant capacities using DPPH and ABTS assays. The results indicated that the straw mushroom exhibited higher levels of polysaccharides, GABA, TPC, and TFC compared to the grey oyster mushroom, which contained higher protein levels. Specifically, the fruiting bodies extract of the straw mushroom demonstrated the highest levels of polysaccharides (416.94 mg/g extract), GABA (12.86 mg/g extract), TPC (33.27 mg GAE/g extract), and TFC (9.39 mg CE/g extract). Furthermore, the fruiting bodies extract showed a greater capacity to scavenge free radicals than the mycelia extract of both straw mushroom and grey oyster mushroom, with DPPH assay values of 0.65 and 0.47 mg TE/g extract and ABTS assay values of 2.26 and 1.74 mg TE/g extract, respectively. These results suggest that the fruiting bodies possess higher free radical scavenging potential as an outcome of their high levels of bioactive compounds. Consequently, these extracts indicate promise as natural antioxidative agents and could be effectively utilized as ingredients in the culinary industry.

GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.

The microcircuitry within superficial layers of the dorsolateral prefrontal cortex (DLPFC), composed of excitatory pyramidal neurons and inhibitory GABAergic interneurons, has been suggested as the neural substrate of working memory performance. In schizophrenia, working memory impairments are thought to result from alterations of microcircuitry within the DLPFC. GABAergic interneurons, in particular, are crucially involved in synchronizing neural activity at gamma frequency, the power of which increases with working memory load. Alterations of GABAergic interneurons, particularly parvalbumin (PV) and somatostatin (SST) subtypes, are frequently observed in schizophrenia. Abnormalities of GABAergic neurotransmission, such as deficiencies in the 67 kDA isoform of GABA synthesis enzyme (GAD67), vesicular GABA transporter (vGAT), and GABA reuptake transporter 1 (GAT1) in presynaptic boutons, as well as postsynaptic alterations in GABA A receptor subunits further contribute to impaired inhibition. This review explores GABAergic abnormalities of the postmortem DLPFC in schizophrenia, with a focus on the roles of interneuron subtypes involved in cognition, and GABAergic neurotransmission within presynaptic boutons and postsynaptic alterations. Where available, comparisons between schizophrenia and affective disorders that share cognitive pathology such as bipolar disorder and major depressive disorder will be made. Challenges in directly measuring GABA levels are addressed, emphasizing the need for innovative techniques. Understanding GABAergic abnormalities and their implications for neural circuit dysfunction in schizophrenia is crucial for developing targeted therapies.

Ferulic Acid-Loaded Nanostructure Maintains Brain Levels of ACh, Glutamate, and GABA and Ameliorates Anxiety and Memory Impairments Induced by the D-Galactose Aging Process in Rats.

Population aging is a global reality driven by increased life expectancy. This demographic phenomenon is intrinsically linked to the epidemic of cognitive disorders such as dementia and Alzheimer's disease, posing challenges for elderly and their families. In this context, the search for new therapeutic strategies to prevent or minimize cognitive impairments becomes urgent, as these deficits are primarily associated with oxidative damage and increased neuroinflammation. Ferulic acid (FA), a natural and potent antioxidant compound, is proposed to be nanoencapsulated to target the central nervous system effectively with lower doses and an extended duration of action. Here, we evaluated the effects of the nanoencapsulated FA on d-galactose (d-Gal)- induced memory impairments. Male Wistar adult rats were treated with ferulic acid-loaded nanocapsules (FA-Nc) or non-encapsulated ferulic acid (D-FA) for 8weeks concurrently with d-Gal (150mg/kg s.c.) injection. As expected, our findings showed that d-Gal injection impaired memory processes and increased anxiety behavior, whereas FA-Nc treatment ameliorated these behavioral impairments associated with the aging process induced by d-Gal. At the molecular level, nanoencapsulated ferulic acid (FA-Nc) ameliorated the decrease in ACh and glutamate induced by d-galactose (d-Gal), and also increased GABA levels in the dorsal hippocampus, indicating its therapeutic superiority. Additional studies are needed to elucidate the mechanisms underlying our current promising outcomes. Nanoscience applied to pharmacology can reduce drug dosage, thereby minimizing adverse effects while enhancing therapeutic response, particularly in neurodegenerative diseases associated with aging. Therefore, the strategy of brain-targeted drug delivery through nanoencapsulation can be effective in mitigating aging-related factors that may lead to cognitive deficits.