Gabapentin increases expression of δ subunit-containing GABA receptors.

Background: Gabapentin is a structural analog of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Its anticonvulsant, analgesic and anxiolytic properties suggest that it increases GABAergic inhibition; however, the molecular basis for these effects is unknown as gabapentin does not directly modify GABA type A (GABA) receptor function, nor does it modify synaptic inhibition. Here, we postulated that gabapentin increases expression of δ subunit-containing GABA (δGABA) receptors that generate a tonic inhibitory conductance in multiple brain regions including the cerebellum and hippocampus.

Glycosylation States of Pre- and Post-synaptic Markers of 5-HT Neurons Differ With Sex and 5-HTTLPR Genotype in Cortical Autopsy Samples.

The serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) is thought to alter 5-HT signaling and contribute to behavioral and cognitive phenotypes in depression as well as Alzheimer disease (AD). We explored how well the short () and long () alleles of the 5-HTTLPR align with serotoninergic indices in 60 autopsied cortical samples from early-onset AD/EOAD and late-onset AD/LOAD donors, and age- and sex-matched controls. Stratifying data by either diagnosis-by-genotype or by sex-by-genotype revealed that the donor's 5-HTTLPR genotype, i.

Systematic screening of generic drugs for progressive multiple sclerosis identifies clomipramine as a promising therapeutic.

The treatment of progressive multiple sclerosis (MS) is unsatisfactory. One reason is that the drivers of disease, which include iron-mediated neurotoxicity, lymphocyte activity, and oxidative stress, are not simultaneously targeted. Here we present a systematic screen to identify generic, orally available medications that target features of progressive MS.

What Goes Around Can Come Around: An Unexpected Deleterious Effect of Using Mouse Running Wheels for Environmental Enrichment.

Environmental enrichment items such as running wheels can promote the wellbeing of laboratory mice. Growing evidence suggests that wheel running simulates exercise effects in many mouse models of human conditions, but this activity also might change other aspects of mouse behavior. In this case study, we show that the presence of running wheels leads to pronounced and permanent circling behavior with route-tracing in a proportion of the male mice of a genetically distinct cohort.

Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature.

A review of studies on the body fluid levels of neuroactive amino acids, including glutamate, glutamine, taurine, gamma-aminobutyric acid (GABA), glycine, tryptophan, D-serine, and others, in autism spectrum disorders (ASD) is given. The results reported in the literature are generally inconclusive and contradictory, but there has been considerable variation among the previous studies in terms of factors such as age, gender, number of subjects, intelligence quotient, and psychoactive medication being taken. Future studies should include simultaneous analyses of a large number of amino acids [including D-serine and branched-chain amino acids (BCAAs)] and standardization of the factors mentioned above.

The MAO inhibitor phenelzine improves functional outcomes in mice with experimental autoimmune encephalomyelitis (EAE).

Multiple sclerosis (MS) and the animal model, experimental autoimmune encephalomyelitis (EAE), are both accompanied by motor and non-motor symptoms. Pathological changes in the activities of key neurotransmitters likely underlie many of these symptoms. We have previously described disturbances in the levels of 5-hydroxytryptamine (5-HT/serotonin), noradrenaline (NE) and γ-aminobutyric acid (GABA) in a mouse model of EAE.

Tissue concentration changes of amino acids and biogenic amines in the central nervous system of mice with experimental autoimmune encephalomyelitis (EAE).

We have characterized the changes in tissue concentrations of amino acids and biogenic amines in the central nervous system (CNS) of mice with MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE), an animal model commonly used to study multiple sclerosis (MS). High performance liquid chromatography was used to analyse tissue samples from five regions of the CNS at the onset, peak and chronic phase of MOG(35-55) EAE. Our analysis includes the evaluation of several newly examined amino acids including d-serine, and the inter-relations between the intraspinal concentration changes of different amino acids and biogenic amines during EAE.

Determination of L-serine-O-phosphate in rat and mouse brain tissue using high-performance liquid chromatography and fluorimetric detection.

L-Serine-O-phosphate (L-SOP), the precursor of l-serine, is an agonist at group III metabotropic glutamate receptors. Despite the interest in L-SOP, very few articles have reported its brain levels. Here we report a convenient and reproducible method for simultaneous analysis of L-SOP and several other important amino acids in brain tissue using high-performance liquid chromatography (HPLC) with fluorimetric detection after derivatization with o-phthaldialdehyde and N-isobutyl-L-cysteine.

Zero net flux estimates of septal extracellular glucose levels and the effects of glucose on septal extracellular GABA levels.

Although hippocampal infusions of glucose enhance memory, we have found repeatedly that septal glucose infusions impair memory when gamma-aminobutyric acid (GABA) receptors are activated. For instance, hippocampal glucose infusions reverse the memory-impairing effects of co-infusions of the GABA agonist muscimol, whereas septal glucose infusions exacerbate memory deficits produced by muscimol. One potential explanation for these deleterious effects of glucose in the septum is that there are higher levels of endogenous extracellular fluid glucose concentrations in the septum than in the hippocampus.

N-Propynyl analogs of beta-phenylethylidenehydrazines: synthesis and evaluation of effects on glycine, GABA, and monoamine oxidase.

A group of beta-phenylethylidenehydrazines possessing a variety of substituents (Me, OMe, Cl, F, and CF(3)) at the ortho-, meta-, or para-positions of the phenyl ring, in conjunction with either a N-bis-(2-propynyl) or a N-mono-(2-propynyl) moiety, were synthesized and compared to the novel neuroprotective drug beta-phenylethylidenehydrazine (PEH) with regard to their ability to inhibit the enzymes GABA-transaminase (GABA-T) and monoamine oxidase (MAO)-A and -B in vitro in brain tissue. Two of the analogs synthesized (mono- and bis-N-propynylPEH) were also studied exvivo in rats to compare their effects to those of PEH with regard to ability to inhibit GABA-T and MAO and to change brain levels of several important amino acids. Unlike PEH, none of the new drugs inhibited GABA-T in vitro at 10 or 100 microM, and all of the drugs (including PEH) were poor inhibitors (at 10 microM) of MAO-A and -B invitro.

The effects of doxycycline administration on amino acid neurotransmitters in an animal model of neonatal hypoxia-ischemia.

Neonatal hypoxia-ischemia (HI) is a major contributor to many neurological, psychiatric and behavioral disorders. Previous studies in our laboratory have shown that a one-time dose of doxycycline (DOXY), even when given 3h after HI insult, was neuroprotective and significantly reduced microglial activation and cleaved caspase-3 protein expression in the immature brain. In light of these data, the goal of this study was to investigate the effects of DOXY administration on amino acid neurotransmitters.