Gamma Amino Research Articles

Wheat and Wheat-Derived Beverages: A Comprehensive Review of Technology, Sensory, Biological Activity, and Sustainability.

At present there is heightened demand for beverages that functionally improve human well-being. Wheat and wheat derivatives are excellent sources of nutrients and bioactive phytochemicals including phenolic compounds, dietary fiber, gamma amino butyric acid, and amino acids. Generally, wheat flour has been used extensively in baking and confectionery production, and wheat germ, and bran are byproducts that can be used to fortify some foods. However, limited attention has been paid to the use of wheat and wheat derivatives for beverage production. Our study therefore aimed to fill this gap by comprehensively exploring various aspects of wheat beverages. This review scrutinizes the use of wheat and wheat derivatives in beverage preparation, including processing methods, sensory perception, and biological properties, and also sheds light on the challenges and future perspectives of the wheat beverage industry. Our study offers valuable insight into the use of wheat for the design of functional, nonalcoholic plant-based beverages.

GABA and nitric oxide reduce AsV toxicity in tomato and brinjal seedlings by regulating sulphur assimilation and proline metabolism

Arsenate (AsV) is one of the most hazardous elements, and its increasing accumulation in plants is the major area of concern in present days. Therefore, an environmentally reliable approach is required to reduce the load of AsV into vegetables. In the current study, the potential role of gamma amino butyric acid (GABA; 10 µM) and sodium nitroprusside a donor of NO (SNP; 10 µM) in 21 days old seedlings of tomato and brinjal grown in Hoagland medium containing 25 µM of AsV was analysed by estimating physiological and biochemical attributes. AsV exposure reduced root and shoot length and dry mass by 18, 9 % and 15 % in tomato, and 23 and 10 %, and 27 % in brinjal seedlings, respectively. Additionally, AsV decreased leaf gas exchange parameters i.e. stomatal conductance, internal CO2 concentration, transpiration rate and subsequently photosynthetic rate. Although AsV stimulated sulphur assimilation and proline metabolism, but it raised the oxidative stress as evident by increased biomarkers; superoxide radicals (SOR), hydrogen peroxide (H2O2), lipid peroxidation (MDA), and protein oxidation in both the seedlings. The application of GABA and SNP significantly mitigated negative effects of AsV on both the vegetables. The results indicate that GABA was unable to reduce AsV stress in the presence of L-NAME (an endogenous NO biosynthetic inhibitor), but addition of SNP rescued the effect of L-NAME. Overall, the findings suggest that GABA and SNP effectively mitigate AsV stress however, the involvement of NO appears to be necessary for GABA to achieve this task efficiently in the studied vegetables. These results will help to design strategies for mitigating arsenate stress in vegetable crops.

Di (2-ethylhexyl) phthalate alters neurobehavioral responses and oxidative status, architecture, and GFAP and BDNF signaling in juvenile rat's brain: Protective role of Coenzyme10

Di-(2-ethylhexyl) phthalate (DEHP), a phthalate plasticizer, is widely spread in the environment, presenting hazards to human health and food safety. Hence, this study examined the probable preventive role of coenzyme10 (CQ10) (10 mg/kg.b.wt) against DEHP (500 mg/kg.wt) - induced neurotoxic and neurobehavioral impacts in juvenile (34 ± 1.01g and 3 weeks old) male Sprague Dawley rats in 35-days oral dosing trial. The results indicated that CQ10 significantly protected against DEHP-induced memory impairment, anxiety, depression, spatial learning disorders, and repetitive/stereotypic-like behavior. Besides, the DEHP-induced depletion in dopamine and gamma amino butyric acid levels was significantly restored by CQ10. Moreover, CQ10 significantly protected against the exhaustion of CAT, GPx, SOD, GSH, and GSH/GSSG ratio, as well as the increase in malondialdehyde, Caspas-3, interleukin-6, and tumor necrosis factor-alpha brain content accompanying with DEHP exposure. Furthermore, CQ10 significantly protected the brain from the DEHP-induced neurodegenerative alterations. Also, the increased immunoexpression of brain-derived neurotrophic factor, not glial fibrillary acidic protein, in the cerebral, hippocampal, and cerebellar brain tissues due to DEHP exposure was alleviated with CQ10. This study's findings provide conclusive evidence that CQ10 has the potential to be used as an efficient natural protective agent against the neurobehavioral and neurotoxic consequences of DEHP.

Comparative effect of preoperative oral pregabalin 50 mg vs. 75 mg on nerve growth factor (NGF) levels in parturients undergoing cesarean section

Background & objectives: Postoperative pain after cesarean section (CS) is a crucial problem faced by the parturients. Pregabalin is a choice of preventive analgesia to reduce neuropathic pain, inflammation, tissue irritation, and post-cesarean section pain. The purpose of this study was to compare the effect of giving pregabalin 50 mg or 75 mg in combination with paracetamol 1 g on nerve growth factor (NGF) levels after cesarean section. 
 Methodology: A prospective, comparative model was used in this study. The study took place at Mother and Children Hospital of Sitti Khadijah I, Makassar, Indonesia. A total of 30 patients who underwent CS were randomly divided into two groups; group P1 who received pregabalin 50 mg orally and 1 g paracetamol intravenously, 1 h before surgery (n = 15), and group P2 who received pregabalin 75 mg orally and 1 g paracetamol intravenously, 1 h before surgery (n = 15). Nerve Growth Factor (NGF) levels were measured 2 h before surgery, and at 4 and 6 h post-surgery. Data were analyzed by the Mann-Whitney test using SPSS 26.0.
 Results: There was a decrease in NGF levels in the pregabalin 75 mg group at 6 h post-surgery, while in the pregabalin 50 mg group it tended to increase at 4 and 6 h post-surgery. In the pregabalin 50 mg group, there was a significant increase in NGF levels from measurements of NGF1 to NGF2 and NGF0 to NGF2 (P < 0.05), whereas, in the pregabalin 75 mg group, there was a significant decrease in NGF levels from measurements of NGF1 to NGF2 and NGF0 to NGF2 (P < 0.05). 
 Conclusion: The combination of pregabalin 75 mg orally with paracetamol 1 g intravenously is effective as perioperative multimodal analgesia by reducing nerve growth factor levels after cesarean section surgery.
 Abbreviations: BDNF- brain-derived neurotrophic factor; CS- Cesarean section; GABA- Gamma Amino Butyric Acid; NGF- Nerve Growth Factor
 Keywords: Cesarean section; Nerve Growth Factor (NGF); Postoperative; Pregabalin
 Citation: Ahmad MR, Harahap MW, Wirawan NS. Comparison between pregabalin 50 mg and 75 mg on nerve growth factor (NGF) levels after cesarean section. Anaesth. pain intensive care 2022;27(6):721−725; DOI: 10.35975/apic.v27i6.2159
 Received: February 20, 2923; Revised: July 11,2023; Accepted: October 29, 2023

Characteristics of GABA (Gamma Amino Butyric Acid), antioxidant and sensory quality of modified Tempeh

ABSTRACTGABA (Gamma Amino Butyric Acid) is a non-protein amino acid that is beneficial to health. Tempeh is a fermentation product with GABA and antioxidant components that contribute to its health-promoting properties. This study aimed to determine the effect of the type of raw material and coloring method on the characteristics of the functional content of modified Tempeh. The research utilized a Completely Randomized Design with raw material types (sorghum, adlay, soybeans, and mung beans) and drying methods (oven drying and freeze-drying) as treatments. The results showed that the type of raw material and drying method had significant effect on the levels of GABA, flavonoids, total phenolic content, and the antioxidant activity of the modified Tempeh. The sorghum tempeh dried with a freeze dryer exhibits the highest GABA content at 1421 mg/100 grams. From a statistical perspective, the antioxidant capacity generated in fresh green bean and soybean tempeh is categorized as moderate. Modified Tempeh made from soybean had sensory acceptance and it did not significantly different from the control.

Acute and sub-acute metabolic change in different brain regions induced by moderate blunt traumatic brain injury.

The objective of the study was to observe the effect of moderate closed-head injury on hippocampal, thalamic, and striatal tissue metabolism with time. Closed head injury is responsible for metabolic changes. These changes can be permanent or temporary, depending on the injury's impact. For the experiment, 20 rats were randomly divided into four groups, each containing five animals. Animals were subjected to injury using a modified Marmarou's weight drop device; hippocampal, thalamic, and striatal tissue samples were collected after 1 day, 3 days, and 7 days of injury. NMR spectra were acquired following sample processing. Changes in myo-inositol, creatine, glutamate, succinate, lactate, and N-acetyl aspartic acid in hippocampal tissues were observed at day 3 PI. The tyrosine level in the hippocampus was altered at day 7 PI. While thalamic and striatal tissue samples showed altered levels of branched-chain amino acids and myo-inositol at day 1PI. Taurine, gamma amino butyric acid (GABA), choline, and alpha keto-glutarate levels were found to be significantly altered in striatal tissues at days 1 and 3PI. Acetate and GABA levels were altered in the thalamus on day 1 PI. The choline level in the thalamus was found to alter at all-time points after injury. The alteration in these metabolites may be due to the alteration in their respective pathways. Neurotransmitter and energy metabolism pathways were found to be altered in all three brain regions after TBI. This study may help better understand the effect of injury on the metabolic balance of a specific brain region and recovery.

Effects of Phragmanthera capitata (Loranthaceae) on a model of anxiety-like behaviours induced by chronic immobilization stress in mice

This work aims to evaluate the anxiolytic-like effects of Phragmanthera capitata in a model of chronic immobilization stress in mice. Groups of mice were treated in ten consecutive days as follows: a normal control group (NaCl 0.9% per os), a negative control group (chronic immobilization stress + NaCl 0.9% per os), three test groups that were submitted to chronic immobilization stress (CIS) and received three doses of the plant (25, 125, and 250 mg/kg, p.o), and a positive control group (chronic immobilization stress + diazepam 2 mg/kg, i.p). Open field and dark/light tests were used for the evaluation of anxiolytic effects. Antioxidant activities and the involvement of gabaergic neurotransmission were determined by measuring the levels of malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), gamma amino butyric acid (GABA), and GABA-transaminase (GABA-T) in the brain. Our results show that the highest dose of Phragmanthera capitata induced a significant increase (p < 0.001) of time spent in the centre, number of crossing and number of grooming in the open field test and a significant increase (p < 0.001) of time spent in the light compartment and the latency of the first escape in the light compartment of the dak/light test. The level of MDA and the activity of GABA-T were significantly decreased by the Phragmanthera capitata while reduced GSH, CAT and GABA, levels were increased. These results suggest that Phragmanthera capitata possesses anxiolytic-like effects that may be supported by its antioxidant activities and or the GABA neurotransmission.

Relationships between GABA, glutamate, and GABA/glutamate and social and olfactory processing in children with autism spectrum disorder

Theories of altered inhibitory/excitatory signaling in autism spectrum disorder (ASD) suggest that gamma amino butyric acid (GABA) and glutamate (Glu) abnormalities may underlie social and sensory challenges in ASD. Magnetic resonance spectroscopy was used to measure Glu and GABA+ levels in the amygdala-hippocampus region and cerebellum in autistic children (n = 30), a clinical control group with sensory abnormalities (SA) but not ASD (n = 30), and children with typical development (n = 37). All participants were clinically assessed using the Autism Diagnostic Interview-Revised, the Autism Diagnostic Observation Scale-2, and the Child Sensory Profile-2. The Social Responsiveness Scale-2, Sniffin Sticks Threshold Test, and the University of Pennsylvania Smell Identification Test were administered to assess social impairment and olfactory processing. Overall, autistic children showed increased cerebellar Glu levels compared to TYP children. Evidence for altered excitatory/inhibitory signaling in the cerebellum was more clear-cut when analyses were restricted to male participants. Further, lower cerebellar GABA+/Glu ratios were correlated to more severe social impairment in both autistic and SA males, suggesting that the cerebellum may play a transdiagnostic role in social impairment. Future studies of inhibitory/excitatory neural markers, powered to investigate the role of sex, may aid in parsing out disorder-specific neurochemical profiles.

Enrichment of gamma-aminobutyric acid (GABA) content using germinated parboiled rice in Thai layered dessert (kanom chan) products

This research aimed to study the Thai layered dessert (Kanom Chan) products, focusing on the composition of germinated parboiled rice, consumer acceptance, nutritional value, GABA content, and the recommended standard recipe. The recipe comprised arrowroot flour, tapioca flour, rice flour, granulated sugar, Jasmine-infused water, undiluted coconut milk, and food coloring in specific proportions.The desserts had visually appealing attributes with distinct layers, captivating colors, a pleasing aroma, a soft texture, and a delightful taste. The recipe received moderate to high satisfaction ratings from taste testers, ranging from 7.40 to 8.18.In the study comparing the substitution of rice flour with germinated parboiled rice flour at three levels (30, 40, and 50% of net weight), desserts with a 30% substitution achieved the highest scores in sensory tests for appearance, colour, smell, taste, and overall preference. The desserts' nutritional value was moderately accepted by 100 consumers. A detailed analysis of 100 g of germinated parboiled rice revealed an energy value of 268.80 kilocalories, along with protein, fat, carbohydrate, moisture, and ash contents of 0.66, 7.44, 49.80, 41.89, and 0.21%, respectively. Additionally, the desserts contained 10.76 mg of gamma amino butyric acid (GABA). Therefore, the germinated parboiled rice Thai layered desserts (Kanom Chan) exhibited low energy and more GABA content compared to general Thai layered dessert.

Successful treatment of concurrent acute migraine headache and atrial fibrillation with benzodiazepine administration

Migraine and atrial fibrillation (AF) are common disorders in the general population in which autonomic nervous system takes role in the pathophysiological mechanism of both diseases. Migraine is a primary headache disease that is associated with significant debilitating symptoms and disability especially among young individuals and AF is associated with excess risk of morbidity and mortality. Interaction between migraine and AF has been a major interest since years at a pathophysiological and clinical level. Benzodiazepines (BZDs) are a class of psychotropic drugs that act through gamma amino butyric acid-A receptors located in the central nervous system. BZDs are widely used for their anxiolytic, anticonvulsant, sedative-hypnotic and muscle relaxant effects. Herein, we describe a case of a patient presenting with concurrent acute migraine headache and AF attack and successful treatment of both conditions simultaneously with intravenous administration of BZD.

Prospective effect of linkers type on the anticancer activity of pemetrexed-monoclonal antibody (atezolizumab) conjugates

Background: Conventional chemotherapy results in severe toxic side effects due to affecting normal and cancer cells. The conjugation of chemotherapy with mAb will improve the chemotherapy selectivity towards cancer cells and at the same time will potentiate immune system to detect and kill cancer cells. The aim of the study was to prepare atezolizumab-pemetrexed conjugate using two types of linkers (linker conjugated with -NH2 of lysine amino acid in the mAb). Methods: This study utilizes (for the first time) the mAb atezolizumab (AtZ) to prepare a new, selective conjugate carrier for pemetrexed (PMX) by using gamma amino butyric acid (GABA) as linker for the first time in comparison to the commonly used linker polyethylene glycol (PEG) using carbodiimide (EDC) / N-hydroxysulfosuccinimide (Sulfo-NHS) zero length cross linker. Stepwise evaluation for PMX-linkers linkage as well as mAb conjugates was evaluated by FTIR, 1HNMR, DSC, LC-MS, gel-electrophoresis as well as the anticancer activity against lung cells A549. Results: The work revealed that two molecules of GABA combined with PMX, which in turn conjugated with an average ratio of 4:1 with mAb, while one molecule of PEG combined with PMX, which in turn conjugated with mAb in the same average ratio. The IC50 for the prepared PMX-GABA-AtZ conjugate was 0.048 µM, which was much lower than PMX alone, antibody AtZ alone as well as PMX-PEG-AtZ conjugate in a dose and time dependent manner. Conclusions: The potential use of such conjugate that selectively directed to the overexpressed lung cells antigen in a low dose leading to reduction of serious side effects of PMX and the cost of therapeutically AtZ mAb used.

Autoimmune encephalitis, a diagnostic and therapeutic challenge in the intensive care unit

Autoimmune encephalitis is a progressive inflammation of the brain, from acute to subacute, associated with antibodies against neuronal cell surface and synaptic protein, most commonly encephalitis against the N-methyl-D-aspartate (NMDA) receptor. New significant findings on etiology show that autoimmune encephalitis is triggered by several etiologies, for example neoplastic processes (breast, lung, kidney, thyroid cancer, ovarian teratoma, and B-cell lymphoma) but also by infections of the nervous system, such as herpes encephalitis. Antibodies against neuronal surface structures are usually direct pathogens and develop their effect through internalization of target proteins, through receptor blockade or complement activation. The type and titer of the antibody e.g. against NMDA receptors, Gamma Amino Butyric (GABA), α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors or voltage-gated potassium channel complexes. An associated tumor, biomarkers, imaging studies, and cerebrospinal fluid are decisive for the prognosis. We present the clinical case of a male patient in the fourth decade of life who is diagnosed with autoimmune encephalitis, we will address the diagnosis and treatment.

Novel Lactone-Based Insecticides and Drosophila suzukii Management: Synthesis, Potential Action Mechanisms and Selectivity for Non-Target Parasitoids.

Drosophila suzukii, an invasive insect pest, poses a significant threat to various fruit crops. The use of broad-spectrum insecticides to control this pest can reduce the effectiveness of biological control agents, such as the parasitoid Trichopria anastrephae. Here, we evaluated the toxicity of newly synthesized lactone derivatives on D. suzukii and their selectivity towards T. anastrephae. We used in silico approaches to identify potential targets from the most promising molecules in the D. suzukii nervous system and to understand potential differences in susceptibilities between D. suzukii and its parasitoid. Of the nine molecules tested, (rac)-8 and compound 4 demonstrated efficacy against the fly. Exposure to the estimated LC90 of (rac)-8 and compound 4 resulted in a mortality rate of less than 20% for T. anastrephae without impairing the parasitoid's functional parasitism. The in silico predictions suggest that (rac)-8 and compound 4 target gamma amino butyric acid (GABA) receptors and transient receptor potential (TRP) channels of D. suzukii. However, only the reduced interaction with TRP channels in T. anastrephae demonstrated a potential reason for the selectivity of these compounds on the parasitoid. Our findings suggest the potential for integrating (rac)-8 and compound 4 into D. suzukii management practices.

Anticonvulsant potential of Grewia tiliaefolia in pentylenetetrazole induced epilepsy: insights from in vivo and in silico studies.

Epilepsy, a chronic neurological condition, impacts millions of individuals globally and remains a significant contributor to both illness and mortality. Available antiepileptic drugs have serious side effects which warrants to explore different medicinal plants used for the management of epilepsy reported in Traditional Indian Medicinal System (TIMS). Therefore, we explored the antiepileptic potential of the Grewia tiliaefolia (Tiliaeceae) which is known for its neuroprotective properties. Aerial parts of G. tiliaefolia were subjected to extraction with increasing order of polarity viz. hexane, chloroform and methanol. Antioxidant potential of hexane, chloroform and methanol extracts ofG. tiliaefoliawas evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay, total antioxidant capacity (TAC) assay, reducing power assay (RPA) and DNA nicking assay. Additionally, quantitative antioxidant assays were also conducted to quantify total phenolic (TPC) and total flavonoid content (TFC). As revealed by in vitro assays, methanol extract was found to contain more phenolic content. Hence, the methanol extract was further explored for its anticonvulsant potential in pentylenetetrazole (PTZ) induced acute seizures in mice. The methanol extract (400mg/kg) significantly increased the latency to occurrence of myoclonic jerks and generalized tonic clonic seizures (GTCS). Additionally, it also reduced duration and seizure severity score associated with GTCS. The Grewia tiliaefolia methanol extract was further screened by Ultra High-Performance Liquid Chromatography (UHPLC) for presence of polyphenolic compounds, among which gallic acid and kaempferol were present in higher amount and were further analysed by in silico study to predict their possible binding sites and type of interactions these compounds show with gamma amino butyric acid (GABA) receptor and glutamate α amino-3- hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu-AMPA) receptor. It was revealed that gallic acid and kaempferol had shown agonistic interaction for GABA receptor and antagonistic interaction for Glu-AMPA receptor. We concluded thatG. tiliaefoliashowed anticonvulsant potential possibly because of gallic acid and kaempferol possibly mediated through GABA and Glu-AMPA receptor.

Changes in physicochemical characteristics and metabolites in the fermentation of goji juice by Lactiplantibacillus plantarum

Untargeted and targeted metabolomics based on LC-MS/MS was applied here to investigate the changes in metabolites following Lactiplantibacillus plantarum (L. plantarum) fermentation of goji juice. The changes in physicochemical characteristics, free amino acid and organic acid levels were quantified. Total phenols, total flavonoids, and antioxidant activity were increased after these L. plantarum fermentation. 31 primary metabolites were screened out by comparison between two groups using multivariate statistical analysis. L. plantarum consumed reducing sugar and most varieties of amino acids. Gamma amino butyric acid (GABA) and phenylacetaldehyde were significantly accumulated via precursor of glutamate and phenylalanine, respectively. Indole-3-lactic acid (ILA) was the characteristic secondary metabolite after fermentation. There were 6.25 and 4.19 mg/L ILA accumulated after LP-D and LP-F fermentation, respectively, whereas it was not detected in goji juice. The accumulation of tyrosol was strain-dependent. Part of the bitter-taste amino acids, including l-methinoine, l-phenylalanine and tryptophan, were converted into their corresponding acetyl-derivatives, which represented umami or kokumi taste. Overall, fermentation by L. plantarum strains altered the metabolite profile and increased the levels of several biologically active substances of goji juice. These results deepen the understanding of L. plantarum metabolism, and the bioconversion associated with flavor and bioactive compounds unraveled here can be used as references in other plant-based materials for LAB fermentation.

Augmentation of gamma amino butyric acid (GABA), antioxidant potential and nutrient qualities in germinated brown rice

Rice grains rich in GABA, a major inhibitory neurotransmitter, are gaining popularity, particularly, in the health food market, for their nutritional, brain, and nerve functions. Many factors like variety, soaking, and germination time influence GABA levels in rice. We evaluated a few indigenous rice varieties/cultivars for their potential to enhance GABA content by varying the soaking and germination durations. GABA content of rice varieties Jyothi and Chitteni and the cultivar Njavara increased steadily from 19.18 mg/kg, 26.67 mg/kg, and 28.63 mg/kg at 0 h soaking and germination to 116.89 mg/kg, 127.97 mg/kg and 130.29 mg/kg after 72 h soaking and germination. The GABA enriched rice extracts showed moderate antioxidant activity in DPPH radical scavenging activity with an IC50 value of 121.01 μg/mL, 101.38 μg/mL, 119.14 μg/mL,and high reducing activity in ferric oxide radical scavenging assay with an IC50 value of 53.81 μg/mL, 47.30 μg/mL, and 52.15 μg/mL in Jyothi, Njavara, and Chitteni, respectively. GABA content enhanced significantly with the increase in the duration of soaking and germination. The germination process for all rice varieties/cultivars significantly (P ≤ 0.05) enhanced protein, fat, and dietary fibre, while the energy and carbohydrate decreased slightly. Among the three rice varieties/cultivars, germinated brown rice from Njavara was superior, having the most GABA content, antioxidant activity, and nutritional qualities. The GABA content in the germinated Njavara was superior or comparable to the GABA content in most of the earlier reported Indian rice varieties. Germinated brown rice from indigenous rice varieties such as Njavara can be exploited as a potential source for a nutritionally rich and balanced diet.

EVALUATION OF ANTIDEPRESSANT AND ANXIOLYTIC ACTIVITY OF OXAPROZIN IN SWISS ALBINO MICE

Depression is a prevalent mental illness. According to estimates, 5 percent of adults worldwide experience depression. Depression affects more women than males. Oxaprozin is a non-narcotic, non-steroidal anti-inflammatory medication (NSAID) used to treat osteoarthritis and rheumatoid arthritis-related inflammation, edoema, stiffness, and joint discomfort. The present study is based on the evaluation of antidepressant and anxiolytic activity of oxaprozin in Swiss albino (either sex) weight 20-25 gm were procured from ICAR-Indian Veterinary Research Institute (ICAR-IVRI), Izzat nagar, Bareilly, Uttar Pradesh. All the mice were divided into 4 groups (n=6) i.e., normal control which was given normal saline, positive control given Imipramine (10mg/kg, i.p.) and diazepam (10mg/kg, subcutaneously), test 1given oxaprozin(10mg/kg, p.o.) and test 2 given Oxaprozin (20mg/kg, p.o.) up to 7 days. The anxiolytic and antidepressant activity were evaluated by parameters i.e., elevated plus maze, FST, rota-rod test and biochemical parameters. It resulted that oxaprozin demonstrates anxiolytic and antidepressant activity. It exhibits antidepressant action probably by facilitating the release of neurotransmitters i. e., serotonin, dopamine. It also increases the release of GABA (Gamma Amino Butyric Acid) and chloride ions influx that leads to hyperpolarization .In conclusion, Oxaprozin is a predominant anxiolytic & anti-depressant drug. It can be effectively used in the treatment of depression, mental agitation and other neurological disorders after successfully evaluating mechanism of action against the same.This study refers, that it might be used in the treatment of depression among human beings after clinical trials.

Association between methylation in the promoter region of the GAD2 gene and opioid use disorder

DNA methylation is one of the epigenetic mechanisms involved in opioid use disorder. GAD2 is a key catalyticase in gamma amino butyric acid (GABA) synthesis from glutamate, that is implicated in opioid-induced rewarding effect. To reveal the relationship and the underlying mechanism between GAD2 gene methylation and opioid use disorder, we first examined and compared the methylation levels in the promoter region of the GAD2 gene in peripheral blood between 120 patients with opioid use disorder and 110 healthy controls by using a targeted approach. A diagnostic model with methylation biomarkers was established to distinguish opioid use disorder and healthy control groups. Correlations between methylation levels in the promoter region of the GAD2 gene and the duration and dosage of opioid use were then determined. Finally, the transcription factors that potentially bind to the target sequences including the detected CpG sites were predicted with the JASPAR database. Our results demonstrated that hypermethylation in the promoter region of the GAD2 gene was associated with opioid use disorder. A diagnostic model based on 10 methylation biomarkers could distinguish the opioid use disorder and healthy control groups. Several correlations between methylation levels in the GAD2 gene promoter and the duration and dosage of opioid use were observed. Transcription factors TFAP2A, Arnt and Runx1 were predicted to bind to the target sequences including several CpG sites detected in the present study in the GAD2 gene promoter. Our findings highlight and extend the role of DNA methylation in the GAD2 gene in opioid use disorder.

Sex-specific differences in the circadian pattern of action potential firing by rat suprachiasmatic nucleus vasopressin neurons.

The suprachiasmatic nucleus (SCN) of the hypothalamus serves as the master circadian clock in mammals. Most SCN neurons express the inhibitory neurotransmitter GABA (gamma amino butyric acid) along with a peptide cotransmitter. Notably, the neuropeptides vasopressin (VP) and vasoactive intestinal peptide (VIP) define two prominent clusters within the SCN: those located in the ventral core (VIP) and those forming the dorsomedial "shell" of the nucleus (VP). Axons emerging from VP neurons in the shell are thought to mediate much of the SCN's output to other brain regions as well as VP release into the cerebrospinal fluid (CSF). Previous work has shown that VP release by SCN neurons is activity dependent and SCN VP neurons fire action potentials at a higher rate during the light phase. Accordingly, CSF VP levels are higher during daytime. Interestingly, the amplitude of the CSF VP rhythm is greater in males than females, suggesting the existence of sex differences in the electrical activity of SCN VP neurons. Here we investigated this hypothesis by performing cell-attached recordings from 1070 SCN VP neurons across the entire circadian cycle in both sexes of transgenic rats that express green fluorescent protein (GFP) driven by the VP gene promoter. Using an immunocytochemical approach we confirmed that >60% of SCN VP neurons display visible GFP. Recordings in acute coronal slices revealed that VP neurons display a striking circadian pattern of action potential firing, but the characteristics of this activity cycle differ in males and females. Specifically, neurons in males reached a significantly higher peak firing frequency during subjective daytime compared to females and the acrophase occurred ~1 h earlier in females. Peak firing rates in females were not significantly different at various phases of the estrous cycle.

Abstract #1394329: An Association Between Stiff Person Syndrome and Type 1 Diabetes

Stiff-person syndrome (SPS) is a rare neuromuscular disorder characterized by progressive muscular spasms and rigidity. Anti-glutamic acid decarboxylase (anti-GAD) antibodies are found in type 1 diabetes mellitus (T1DM). Thirty percent of patients diagnosed with SPS have T1DM. This relationship infers that SPS and T1DM share pathogenetic features. We describe a case of a 66-year-old female with a history of SPS who developed T1DM soon after the diagnosis was made. A 66-year-old female with a history of SPS, T1DM, and discoid lupus was referred to our university endocrinology clinic for diabetes management. She had ataxia, loss of balance, and muscle stiffness since 2012. The patient was diagnosed with spinal cerebellar ataxia. She was not treated with any specific agents and continued to have left-sided muscle stiffness with preserved strength. She denied weakness, pain, paresthesia, or muscle atrophy but had difficulty ambulating due to rigidity. The diagnosis of SPS was made based on positive anti-GAD antibodies (normal < 0.02) and positive N-channel antibodies in April 2016. She required hospital admission one month later and received solumedrol and IVIG. Her HbA1c was 6.5% (normal < 5.7% of total Hgb), and glucose levels were between 200-300 mg/dL, which were treated with basal and bolus insulin. She was discharged home in May 2016 with no diabetic medications. The patient developed polyuria and polydipsia with 11 Ibs unintentional weight loss 20 days after hospital discharge. She was referred to the endocrine clinic in June 2016 for further workup. Her HbA1c was 11% with C-peptide less than 0.01 (normal 0.78-5.20 ng/mL). Basal and bolus insulin were initiated, and she remains on an insulin regimen. SPS affects an estimated one person per million per year. Decreased level of gamma amino butyric acid (GABA) in the central nervous system (CNS) in SPS has been implicated, which causes a loss of neural inhibition. Glutamic acid decarboxylase (GAD) is the main enzyme required for the GABA inhibitory pathway. Anti-GAD antibodies decrease inhibitory function within the CNS and cause increased muscle activities and subsequent muscle spasms. While most patients with T1DM do not develop SPS, most with anti-GAD-positive SPS will have or develop T1DM. Either SPS or T1DM may be diagnosed first. Awareness of these associations is essential for early diagnosis and treatment of these disorders.