Levels Of Glutamic Decarboxylase Research Articles

Dietary supplementation with grape seed extract from Vitus vinifera prevents suppression of GABAergic protein expression in female Sprague Dawley trigeminal ganglion in a model of chronic temporomandibular joint disorder

ObjectiveTo investigate cellular changes in protein expression in the trigeminal ganglion in an established preclinical chronic model of temporomandibular joint disorder (TMD) in response to grape seed extract (GSE) supplementation based on its beneficial use in preclinical chronic orofacial pain models. DesignThree experimental conditions included female Sprague-Dawley rats as naïve controls, and animals subjected to neck muscle inflammation and prolonged jaw opening with and without daily supplementation of GSE in the drinking water prior to inflammation. Changes were evaluated in mechanical sensitivity to von Frey filaments and protein expression in the trigeminal ganglion of animals 14 days post jaw opening. ResultsCalcitonin-gene related peptide and protein kinase A, proteins positively associated with peripheral sensitization and enhanced nociception, did not show elevated expression at day 14 in the model compared to naïve or GSE supplemented animals. However, neuronal levels of glutamate decarboxylase (GAD) 65/67, which are enzymes responsible for the synthesis of the inhibitory neurotransmitter GABA that functions to suppress neuronal excitability, were significantly decreased on day 14 post jaw opening. Similarly, a significant decrease in neuronal expression of the GABA receptor subunits GABAB1 and GABAB2, but not GABAA, was observed in the TMD model. Importantly, GSE prevented suppression of GAD 65/67 and GABAB subunits, maintaining levels similar to naïve animals. ConclusionResults from our study provide evidence of the downregulation of inhibitory GABAergic proteins in trigeminal ganglion neurons in a preclinical chronic TMD model and the benefits of GSE supplementation in preventing their suppression and maintaining normal levels.

The metabolism of amino acids, AsA and abscisic acid induced by strigolactone participates in chilling tolerance in postharvest zucchini fruit.

Zucchini fruit are notably susceptible to chilling injury when stored at low temperatures. The purpose of this experimental investigation was to assess the influence of strigolactone (ST) (5 μmol L-1) on mitigating chilling injury and the metabolic changes in amino acids, ascorbic acid, and abscisic acid in zucchini fruit stored at 4°C. Research findings demonstrated that ST-treated zucchini fruit displayed a significantly higher tolerance to chilling stress compared to the control group. Postharvest ST treatment led to a decrease in weight loss, accompanied by reduced levels of malondialdehyde and relative ion leakage compared to the untreated group. ST immersion significantly boosted the metabolic pathways associated with proline and arginine, affecting both the enzymatic reactions and gene expressions, thus cumulatively increasing the internal concentrations of these amino acids in zucchini fruit. Zucchini treated with ST exhibited an increased concentration of γ-aminobutyric acid (GABA) as a result of augmented activities and elevated transcriptional levels of glutamate decarboxylase (GAD), GABA transaminase (GAT), and succinate semialdehyde dehydrogenase (SSD). In the ST-treated sample, the elevated enzymatic activities and enhanced gene expressions within the ascorbic acid (AsA) biosynthesis pathway worked together to sustain AsA accumulation. The application of ST resulted in a rise in abscisic acid (ABA) concentration, which correspondingly correlated with the induction of both activities and gene expression levels of crucial enzymes involved in ABA metabolism. Our findings revealed that submerging zucchini fruit in ST could be a highly effective strategy for boosting their chilling tolerance. The alleviation in chilling injury induced by ST may be attributed to the modulation of proline, arginine, GABA, AsA and ABA metabolism.

Ultrasonic treatment to enhance seed germination and vigour of wheat (Triticum durum) in association with γ-aminobutyric acid (GABA) shunt pathway.

Treatments of wheat (Triticum durum L.) seeds with sonication or hydropriming may enhance seed germination and vigour in association with γ-aminobutyric acid (GABA). Therefore, the objective of this study is to examine the effect of sonication and hydropriming treatments on seed germination of wheat through the characterisation of seed germination performance, GABA shunt metabolite level (GABA, glutamate, and alanine), and the level of glutamate decarboxylase (GAD) mRNA transcription. Wheat seeds were exposed to three treatments for 0, 5, 10, 15, and 20min: (1) sonication with water; (2) sonication without water; and (3) hydropriming without sonication. Treated seeds were evaluated for germination percentage, mean time to germinate, germination rate index in the warm germination test, and seedling emergence and shoot length in the cold test. GABA shunt metabolites level (GABA, glutamate, and alanine), and the level of GAD mRNA transcription were measured for the seeds after treatments and for seedlings during germination and cold tests. Seeds treated with sonication or hydropriming treatments had a higher germination rate index (faster germination) in the standard germination test, and higher seedling emergence and shoot length in the cold test. Seeds treated with sonication or hydropriming treatments showed an enhancement in GABA shunt and their metabolites (alanine and glutamate), and GAD mRNA transcription level compared to untreated-control seeds. In conclusion, the sonication or hydropriming treatments significantly improved the germination performance of wheat and enhanced GABA metabolism to maintain the C:N metabolic balance, especially under cold stress.

Visualization of Glutamate Decarboxylase Activity in Barley Seeds under Salinity Stress Using Mass Microscope.

γ-Aminobutyric acid (GABA) accumulates in plants in response to environmental stresses. The activity levels of glutamate decarboxylase (GAD), an enzyme involved in GABA biosynthesis, are reported to increase during germination under salinity stress. However, it is not clear which tissues of the plant seeds are affected by GAD activity in response to salinity stress. In this study, the effects of salinity stress on the distribution of barley seeds GAD activity during germination were investigated. The mass spectrometry imaging (MSI) method was optimized, and the distribution of GAD activity in germinated seeds exposed to salinity stress at different germination stages from 12 to 48 h after imbibition was investigated. In this study, MSI was successfully applied to enzyme histochemistry to visualize the relative GAD activity in germinating barley seeds for the first time. The salinity stress increased the GAD activity, mostly due to the increase in relative GAD activity in the embryo. Higher GAD activity was detected in seeds exposed to salinity stress in the scutellum or aleurone layer, which are difficult to separate for extraction. This method can be used to clarify the role of GABA shunts, including GAD enzyme responses, in barley seeds under stress.

Interference of endogenous benzoic acid with the signatures of sulfonic acid derivatives and carbohydrates in fermented dairy products

Endogenous benzoic acid causes detrimental effects on public health, but the underlying mechanisms often remain elusive. Benzoic acid (0.00–40.00 mg L−1) was detected from sixty fermented goat milk samples in six replicates, indicating the existence of endogenous benzoic acid. Herein, we investigated the effects of benzoic acid on the variations of metabolome and proteome signatures in fermented goat milk via integrative metabolomics (LOQ 2.39–98.98 μg L−1) and proteomics approach based on UHPLC-Q-Orbitrap HRMS. Explicitly, benzoic acid reduced the content of taurine (7.06–4.80 mg L−1) and hypotaurine (3.86–1.74 mg L−1) due to a significant decrease in the levels of glutamate decarboxylase 1 by benzoic acid. The reduction in lactose (7.13–5.31 mg L−1) and d-galactose (4.39–3.37 mg L−1) content was related to the decrease in α-lactalbumin and β-galactosidase levels, respectively, in fermented goat milk containing 40.00 mg L−1 benzoic acid. Meanwhile, the levels of maltose (22.84–16.53 mg L−1) and raffinose (4.19–3.10 mg L−1) progressively decreased with increasing benzoic acid concentrations (0.00–40.00 mg L−1), which had detrimental effects on the nutritional quality of fermented goat milk. Additionally, the concentration of benzoic acid and fermentation temperature are the most important factors to control the loss of nutrients in fermented dairy products.

Thymoquinone-rich black cumin oil attenuates ibotenic acid-induced excitotoxicity through glutamate receptors in Wistar rats

Inflammation-mediated alterations in glutamate neurotransmission constitute the most important pathway in the pathophysiology of various brain disorders. The excessive signalling of glutamate results in excitotoxicity, neuronal degeneration, and neuronal cell death. In the present study, we investigated the relative efficacy of black cumin (Nigella sativa) oil with high (5 % w/w) and low (2 % w/w) thymoquinone content (BCO-5 and BCO-2, respectively) in alleviating ibotenic acid-induced excitotoxicity and neuroinflammation in Wistar rats. It was found that BCO-5 reversed the abnormal behavioural patterns and the key inflammatory mediators (TNF-α and NF-κB) when treated at 5 mg/kg body weight. Immunohistochemical studies showed the potential of BCO-5 to attenuate the glutamate receptor subunits NMDA and GluR-2 along with increased glutamate decarboxylase levels in the brain tissues. Histopathological studies revealed the neuroprotection of BCO-5 against the inflammatory lesions, as evidenced by the normal cerebellum, astrocytes, and glial cells. BCO-2 on the other hand showed either a poor protective effect or no effect even at a 4-fold higher concentration of 20 mg/kg body weight indicating a very significant role of thymoquinone content on the neuroprotective effect of black cumin oil and its plausible clinical efficacy in counteracting the anxiety and stress-related neurological disorders under conditions such as depression and Alzheimer's disease.

Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association With Genetic and Clinical Characteristics.

The importance of the autoantibody level at diagnosis of type 1 diabetes (T1D) is not clear. We aimed to assess the association of glutamate decarboxylase (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) autoantibody levels with clinical and genetic characteristics at diagnosis of T1D. We conducted a prospective, cross-sectional study. GADA, IA-2A, and ZnT8A were measured in 1644 individuals with T1D at diagnosis using radiobinding assays. Associations between autoantibody levels and the clinical and genetic characteristics for individuals were assessed in those positive for these autoantibodies. We performed replication in an independent cohort of 449 people with T1D. GADA and IA-2A levels exhibited a bimodal distribution at diagnosis. High GADA level was associated with older age at diagnosis (median 27 years vs 19 years, P = 9 × 10-17), female sex (52% vs 37%, P = 1 × 10-8), other autoimmune diseases (13% vs 6%, P = 3 × 10-6), and HLA-DR3-DQ2 (58% vs 51%, P = .006). High IA-2A level was associated with younger age of diagnosis (median 17 years vs 23 years, P = 3 × 10-7), HLA-DR4-DQ8 (66% vs 50%, P = 1 × 10-6), and ZnT8A positivity (77% vs 52%, P = 1 × 10-15). We replicated our findings in an independent cohort of 449 people with T1D where autoantibodies were measured using enzyme-linked immunosorbent assays. Islet autoantibody levels provide additional information over positivity in T1D at diagnosis. Bimodality of GADA and IA-2A autoantibody levels highlights the novel aspect of heterogeneity of T1D. This may have implications for T1D prediction, treatment, and pathogenesis.

In silico analysis of bacterial metabolism of glutamate and GABA in the gut in a rat model of obesity and type 2 diabetes.

Dysbiosis of gut microbiota has adverse effects on host health. This study aimed to determine the effects of changes of faecal microbiota in obese and diabetic rats on the imputed production of enzymes involved in the metabolism of glutamate, gamma-aminobutyric acid (GABA), and succinate. The levels of glutamate decarboxylase, GABA transaminase, succinate-semialdehyde dehydrogenase, and methylisocitrate lyase were reduced or absent in diabetic rats compared with controls and obese rats. Glutamate decarboxylase (GAD) was significantly reduced in obese rats compared with control rats, while the other enzymes were unaltered; different bacterial taxa are suggested to be involved. Levels of bacterial enzymes were inversely correlated with the blood glucose level. These findings suggest that the absence of GABA and reduced succinate metabolism from gut microbiota contribute to the diabetic state in rats.

Responses of GABA shunt coupled with carbon and nitrogen metabolism in poplar under NaCl and CdCl2 stresses.

The γ-aminobutyric acid (GABA) shunt is closely associated with plant tolerance; however, little is known about its mechanism. This study aimed to decipher the responses of the GABA shunt and related carbon-nitrogen metabolism in poplar seedlings (Populus alba×Populus glandulosa) treated with different NaCl and CdCl2 concentrations for 30h. The results showed that the activities of glutamate decarboxylase (GAD) and GABA-transaminase (GABA-T) were activated, as well as α-ketoglutarate dehydrogenase (α-KGDH) and succinate dehydrogenase (SDH) activities were enhanced by NaCl and CdCl2 stresses, except for SDH under CdCl2 stress. Meanwhile, the expression levels of GADs, GABA-Ts SDHs, succinyl-CoA ligases (SCSs), and succinic acid aldehyde dehydrogenases (SSADHs) were also increased. Notably, significant increases in the key components of GABA shunt, Glu and GABA, were observed under both stresses. Soluble sugars and free amino acids were enhanced, whereas citrate, malate and succinate were almost inhibited by both NaCl and CdCl2 stresses except that citrate was not changed or just increased by 50-mM NaCl stress. Thus, these results suggested that the carbon-nitrogen balance could be altered by activating the GABA shunt when main TCA-cycle intermediates were inhibited under NaCl and CdCl2 stresses. This study can enhance the understanding about the functions of the GABA shunt in woody plants under abiotic stresses and may be applied to the genetic improvement of trees for phytoremediation.

Synaptic deficits in iPSC-derived cortical interneurons in schizophrenia are mediated by NLGN2 and rescued by N-acetylcysteine

Human postmortem studies suggest a major role for abnormalities in GABAergic interneurons in the prefrontal cortex in schizophrenia. Cortical interneurons differentiated from induced pluripotent stem cells (iPSCs) of schizophrenia subjects showed significantly lower levels of glutamate decarboxylase 67 (GAD67), replicating findings from multiple postmortem studies, as well as reduced levels of synaptic proteins gehpyrin and NLGN2. Co-cultures of the interneurons with excitatory cortical pyramidal neurons from schizophrenia iPSCs showed reduced synaptic puncta density and lower action potential frequency. NLGN2 overexpression in schizophrenia neurons rescued synaptic puncta deficits while NLGN2 knockdown in healthy neurons resulted in reduced synaptic puncta density. Schizophrenia interneurons also had significantly smaller nuclear area, suggesting an innate oxidative stressed state. The antioxidant N-acetylcysteine increased the nuclear area in schizophrenia interneurons, increased NLGN2 expression and rescued synaptic deficits. These results implicate specific deficiencies in the synaptic machinery in cortical interneurons as critical regulators of synaptic connections in schizophrenia and point to a nexus between oxidative stress and NLGN2 expression in mediating synaptic deficits in schizophrenia.

Pinellia Total Alkaloids Modulate the GABAergic System in Hippocampal Formation on Pilocarpine-Induced Epileptic Rats.

To investigate the neuromodulatory effect of pinellia total alkaloids (PTA) on the gamma-aminobutyric acidergic (GABAergic) system in epileptic rats, and preliminarily evaluate the anti-epileptic effect of PTA. Ninety-one male Sprague-Dawley rats were randomized to a control group (n=17) or an epileptic group (n=74) using computer-generated random numbers. Status epilepticus (SE) was induced with pilocarpine in the epileptic group. Epileptic rats that survived SE were randomly divided into 4 groups, namely an epilepsy group (n=13), a topiramate (TPM, 60 mg/kg) group (n=12), a high-dose PTA (800 mg/kg) group (n=12), and a low-dose PTA (400 mg/kg) group (n=10). Treatments were given intragastrically once daily for 14 days. The control group and epilepsy group received normal saline. Spontaneous recurrent seizures (SRSs) were monitored 8-h daily for 7 days after treatment. Then, the hippocampal formation tissues were collected. GABA level was measured using enzyme-linked immunosorbent assay. Protein and mRNA expression levels of glutamate decarboxylase 65 (GAD65), GABA transporter-1 (GAT-1), GABA transaminase (GABA-T), and GABAA receptor (GABAAR) α4, α5, γ2 and δ subunits were measured using Western-blotting analysis and quantitative polymerase chain reaction. PTA lowered the incidence and frequency of SRS (both doses vs. the TPM group, P>0.05). Compared with the epilepsy group, PTA increased the levels of GABA (both doses P<0.01) and GAD65 (mRNA, 800 mg/kg, P<0.01), and suppressed the levels of GAT-1 (mRNA, 800 mg/kg, P<0.01; 400 mg/kg, P<0.05), GABA-T (mRNA, both doses P<0.01), and GABAAR δ subunit (protein, 800 mg/kg, P<0.05) and γ2 subunit (protein, both doses P<0.01). PTA upregulated the low-expressed mRNA levels of GABAAR α5 subunit (400 mg/kg, P<0.01), δ subunit (800 mg/kg, P<0.05), and γ2 subunit (400 mg/kg, P<0.05). PTA regulated the GABAergic system through modulating GABA levels and the expression levels of GAD65, GAT-1, GABA-T, and GABAAR α4, α5, γ2 and δ subunits. PTA may exert anti-epileptic effects on the pilocarpine-induced epilepsy model.

Capacitation of mouse sperm is modulated by gamma-aminobutyric acid (GABA) concentration.

In mammals, ejaculated sperm acquire their fertilizing ability during migration through the female reproductive tract, which secretes several factors that contribute to sperm capacitation. Gamma-aminobutyric acid (GABA) is a well-known neurotransmitter in the central nervous system, but additionally enhances the sperm acrosome reaction in the rat and cow. However, the detailed effects of GABA concentration on sperm function remain unclear. In this study, we detected the presence of the GABA type A receptor (GABA A) in mouse epididymal sperm by western blot analysis and in the sperm acrosome by immunocytochemistry. We also investigated the effects of GABA on sperm fertilizing ability. We found that GABA facilitated the tyrosine phosphorylation of sperm proteins, which is an index of sperm capacitation. GABA also promoted the acrosome reaction, which was suppressed by a selective GABA A receptor antagonist. We then found that the effective GABA concentration for the acrosome reaction corresponds to sperm concentration, but we did not detect any marked effect of GABA on sperm motility using a computer-assisted sperm analysis system. Using immunohistochemistry, we also detected GABA expression in the epithelia of the mouse uterus and oviduct. Furthermore, we found that the mRNA levels of glutamate decarboxylase (Gad), which generates GABA from L-glutamate, were higher in the oviduct than in the uterus, and that Gad mRNA levels were higher at estrus than at the diestrus stage. These results indicate that the GABA concentration can act as a modulator of the acrosome reaction and sperm capacitation in the female reproductive tract.

Gamma-Aminobutyric Acid (GABA) Modulates Nitrate Concentrations and Metabolism in the Leaves of Pakchoi (Brassica campestris ssp. chinensis Makino) Treated with a Nitrogen-Rich Solution

Pakchoi plants were grown in 32 mM NO3− nutrient solution with or without 2.5 mM γ-aminobutyric acid (GABA) to investigate metabolite changes, gene and protein expression levels, and the activities of key enzymes related to nitrate metabolism in the leaves over a period of 0–12 days. High-nitrogen treatment enhanced plant growth and the NO3−, NO2−, NH4+, Gln, and Glu contents in the leaves; promoted the gene and protein expression of nitrate reductase (NR) and glutamate decarboxylase (GAD); and increased the activities of NR, nitrite reductase (NiR), glutamine synthetase (GS), glutamate synthase (GOGAT), and GAD. The endogenous GABA concentration in the leaves was enhanced in parallel with the increase in GAD activity. The GABA-treated leaves displayed the greatest increases in the gene and protein expression levels of NR and GAD and in the activities of NR, NiR, GS, GOGAT, and GAD. In addition, accelerated rates of nitrate reduction and assimilation were detected, and these changes occurred concurrently with the observed increases in gene or protein expression and enzyme activity. As a result, the concentrations of NH4+, Gln, Glu, and endogenous GABA were significantly elevated, and the NO3− and NO2− contents were significantly decreased, in GABA-treated leaves compared with plants exposed to nitrogen-rich conditions. Our results reveal a potential positive that GABA may act as a nitrogen source to improve the plant growth and the most prominent effect of decreasing nitrate contents by accelerating NO3− reduction and assimilation. Exogenous GABA plays an important role in reducing the NO3− content of leaves, and thereby improves the ability to harvest leafy vegetables containing higher levels of endogenous GABA.

Response of the GABAergic System to Axotomy of the Rat Facial Nerve.

The responses of inhibitory neurons/synapses to motoneuron injury in the cranial nervous system remain to be elucidated. In this study, we analyzed GABAA receptor (GABAAR) and GABAergic neurons at the protein level in the transected rat facial nucleus. Immunoblotting revealed that the GABAARα1 protein levels in the axotomized facial nucleus decreased significantly 5-14 days post-insult, and these levels remained low for 5 weeks. Immunohistochemical analysis indicated that the GABAARα1-expressing cells were motoneurons. We next examined the specific components of GABAergic neurons, including glutamate decarboxylase (GAD), vesicular GABA transporter (VGAT) and GABA transporter-1 (GAT-1). Immunoblotting indicated that the protein levels of GAD, VGAT and GAT-1 decreased transiently in the transected facial nucleus from 5 to 14 days post-insult, but returned to the control levels at 5 weeks post-insult. Although GABAARα1 protein levels in the transected nucleus did not return to their control levels for 5 weeks post-insult, the administration of glial cell line-derived neurotrophic factor at the cut site significantly ameliorated the reductions. Through these findings, we verified that the injured facial motoneurons suppressed the levels of GABAARα1 protein over the 5 weeks post-insult, presumably due to the deprivation of neurotrophic factor. On the other hand, the levels of the GAD, VGAT and GAT-1 proteins in GABAergic neurons were transiently reduced in the axotomized facial nucleus at 5-14 days post-insult, but recovered at 4-5 weeks post-insult.

An H-NS Family Protein, Sfh, Regulates Acid Resistance by Inhibition of Glutamate Decarboxylase Expression in Shigella flexneri 2457T.

The glutamate-dependent acid-resistance system is the most effective acid tolerance pathway in Shigella, allowing survival in extremely acidic environments. However, the regulation of this system in Shigella remains elusive. In the current study, we identified significant differences in the levels of glutamate decarboxylase between three Shigella flexneri strains with different levels of acid resistance using blue native-polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing (IEF)/sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The results showed that the degree of acid resistance and the levels of GadA/B were significantly lower in strain 2457T compared with two other S. flexneri strains. It has been reported that plasmid pSf-R27 is expressed in strain 2457T but not in the other 142 sequenced S. flexneri isolates. pSf-R27 encodes protein Sfh, which belongs to a family of histone-like nucleoid-structuring (H-NS) proteins that participate in the transcriptional control of glutamate-dependent acid resistance, implicating pSf-R27 in the lower acid resistance of strain 2457T. Transformation of pSf-R27 or sfh alone into strain 301 resulted in decreased expression of GadA/B in the recombinant strains. Thus, we confirmed that H-NS family protein Sfh, bound to the gadA/B regulatory region and regulates the expression of glutamate decarboxylase at the transcriptional level. We also examined the acid tolerance of the wild-type and recombinant strains using flow cytometry and determined that the acid tolerance of S. flexneri is closely related to the expression of GadA/B. These findings further our understanding of the acid tolerance of S. flexneri, especially via the glutamate-dependent pathway.

Effects of Aged Garlic Extract on Cholinergic, Glutamatergic and GABAergic Systems with Regard to Cognitive Impairment in Aβ-Induced Rats.

Alzheimer’s disease (AD) has been linked to the degeneration of central cholinergic and glutamatergic transmission, which correlates with progressive memory loss and the accumulation of amyloid-β (Aβ). It has been claimed that aged garlic extract (AGE) has a beneficial effect in preventing neurodegeneration in AD. Therefore, the objective of this study was to investigate the effects of AGE on Aβ-induced cognitive dysfunction with a biochemical basis in the cholinergic, glutamatergic, and GABAergic systems in rats. Adult male Wistar rats were orally administered three doses of AGE (125, 250, and 500 mg/kg) daily for 65 days. At day 56, they were injected with 1 μL of aggregated Aβ (1–42) into each lateral ventricle, bilaterally. After six days of Aβ injection, the rats’ working and reference memory was tested using a radial arm maze. The rats were then euthanized to investigate any changes to the cholinergic neurons, vesicular glutamate transporter 1 and 2 proteins (VGLUT1 and VGLUT2), and glutamate decarboxylase (GAD) in the hippocampus. The results showed that AGE significantly improved the working memory and tended to improve the reference memory in cognitively-impaired rats. In addition, AGE significantly ameliorated the loss of cholinergic neurons and increased the VGLUT1 and GAD levels in the hippocampus of rat brains with Aβ-induced toxicity. In contrast, the VGLUT2 protein levels did not change in any of the treated groups. We concluded that AGE was able to attenuate the impairment of working memory via the modification of cholinergic neurons, VGLUT1, and GAD in the hippocampus of Aβ-induced rats.

Maternal vitamin B6 deficient or supplemented diets on expression of genes related to GABAergic, serotonergic, or glutamatergic pathways in hippocampus of rat dams and their offspring.

Vitamin B6 plays crucial roles on brain development and its maternal deficiency impacts the gamma-aminobutyric acid (GABA)ergic, serotonergic, glutamatergic, and dopaminergic systems in offspring. However, the molecular mechanisms underlying these neurological changes are not well understood. Thus, we aimed at evaluating which components of those neurotransmitter metabolism and signaling pathways can be modulated by maternal vitamin B6 -deficient or B6 -supplementated diets in the hippocampus of rat dams and their offspring. Female Wistar rats were fed three different diets: control (6 mg vitamin B6 /kg), supplemented (30 mg vitamin B6 /kg) or deficient diet (0 mg vitamin B6 /kg), from 4 weeks before pregnancy through lactation. Newborn pups (10 days old) from rat dams fed vitamin B6 -deficient diet presented hyperhomocysteinemia and had a significant increase in mRNA levels of glutamate decarboxylase 1 (Gad1), fibroblast growth factor 2 (Fgf2), and glutamate-ammonia ligase (Glul), while glutaminase (Gls) and tryptophan hydroxylase 1 (Tph1) mRNAs were downregulated. Vitamin B6 supplementation or deficiency did not change hippocampal global DNA methylation. A maternal vitamin B6 -deficient diet affects the expression of genes related to GABA, glutamate, and serotonin metabolisms in offspring by regulating Gad1, Glul, Gls, and Tph1 mRNA expression.

Modulation of gene expression in guinea pig paraflocculus after induction of hearing loss.

Hearing loss often results in plastic changes in the central auditory pathways, which may be involved in the generation of tinnitus, a phantom auditory sensation. However, although animal studies have consistently shown increased neural activity in auditory structures after hearing loss, tinnitus does not always develop. It has therefore been suggested that non-auditory structures perform a gating or regulatory role that determines whether the increased activity in auditory structures leads to conscious perception. Recent evidence points to the paraflocculus of the cerebellum as having such a role. Therefore, we investigated the early effects of hearing loss on gene expression in guinea pig paraflocculus. Gene expression was investigated after two weeks recovery from either acoustic or mechanical cochlear trauma. The genes investigated in our study were associated with inhibitory neurotransmission (GABA-A receptor subunit alpha 1; glutamate decarboxylase 1), excitatory neurotransmission (glutamate receptor NMDA subunit 1), and regulation of transmitter release (member of RAB family of small GTPase). Our results show increased mRNA levels of glutamate decarboxylase 1 in ipsilateral paraflocculus with no difference between the different methods of cochlear trauma. Early modulation of gene expression in the paraflocculus suggests that an early effect of hearing loss may affect the influence of this structure on auditory processing.

Modulation of gene expression in guinea pig paraflocculus after induction of hearing loss

Hearing loss often results in plastic changes in the central auditory pathways, which may be involved in the generation of tinnitus, a phantom auditory sensation. However, although animal studies have consistently shown increased neural activity in auditory structures after hearing loss, tinnitus does not always develop. It has therefore been suggested that non-auditory structures perform a gating or regulatory role that determines whether the increased activity in auditory structures leads to conscious perception. Recent evidence points to the paraflocculus of the cerebellum as having such a role. Therefore, we investigated the early effects of hearing loss on gene expression in guinea pig paraflocculus. Gene expression was investigated after two weeks recovery from either acoustic or mechanical cochlear trauma. The genes investigated in our study were associated with inhibitory neurotransmission (GABA-A receptor subunit alpha 1; glutamate decarboxylase 1), excitatory neurotransmission (glutamate receptor NMDA subunit 1), and regulation of transmitter release (member of RAB family of small GTPase). Our results show increased mRNA levels of glutamate decarboxylase 1 in ipsilateral paraflocculus with no difference between the different methods of cochlear trauma. Early modulation of gene expression in the paraflocculus suggests that an early effect of hearing loss may affect the influence of this structure on auditory processing.

Modulation of gene expression in guinea pig paraflocculus after induction of hearing loss

Hearing loss often results in plastic changes in the central auditory pathways, which may be involved in the generation of tinnitus, a phantom auditory sensation. However, although animal studies have consistently shown increased neural activity in auditory structures after hearing loss, tinnitus does not always develop. It has therefore been suggested that non-auditory structures perform a gating or regulatory role that determines whether the increased activity in auditory structures leads to conscious perception. Recent evidence points to the paraflocculus of the cerebellum as having such a role. Therefore, we investigated the early effects of hearing loss on gene expression in guinea pig paraflocculus. Gene expression was investigated after two weeks recovery from either acoustic or mechanical cochlear trauma. The genes investigated in our study were associated with inhibitory neurotransmission (GABA-A receptor subunit alpha 1; glutamate decarboxylase 1), excitatory neurotransmission (glutamate receptor NMDA subunit 1), and regulation of transmitter release (member of RAB family of small GTPase). Our results show increased mRNA levels of glutamate decarboxylase 1 in ipsilateral paraflocculus with no difference between the different methods of cochlear trauma. Early modulation of gene expression in the paraflocculus suggests that an early effect of hearing loss may affect the influence of this structure on auditory processing.