T-cell-mediated loss of pancreatic beta-cells is the crucial event in the development of type 1 diabetes. The phenotypic characteristics of disease-associated T-cells in type 1 diabetes have not yet been defined. The negative results from two intervention trials (the Diabetes Prevention Trial-Type 1 Diabetes and the European Nicotinamide Diabetes Intervention Trial) illustrate the need for tech...

tem (CNS), the (GATs). The predominant neuronal GABA transporter GAT1 is localized in GABAergic axons and nerve terminals, where it is thought to influence GABAergic synaptic transmission, but the details rain of GAT1 pocampal GABAAwaveform or amplitude y of quantal GABA release was one-third of WT, although the densities of GABAA-receptors, GABABt mice lacked a requency of ced extracellular on...

gamma-Aminobutyric acid (GABA)-mediated neurotransmission from the granule cells to CA3 is transiently expressed during the first 3 weeks of age in the rat. In the adult, seizures provoke this inhibitory signaling to reappear. To gain insight into the origin of GABA in these cells, we explored the expression of both isoforms of glutamic acid decarboxylase (GAD, 65 and 67 kDa), during developmen...

Autoimmune disease and/or autoantibodies have been reported in mood disorder patients. We screened for autoantibodies to glutamic acid decarboxylase (GAD65), thyroid peroxidase (TPO), gastric H+/K+ ATPase (ATP4B), and Ro52 in a psychiatric patient cohort. A 24-year-old woman with major depressive disorder (MDD) with reduced psychomotor activity was identified with unusually high serum GAD65 and...

Posttranslational modification (PTM) of self-proteins has been shown to elicit clinically relevant immune responses in rheumatoid arthritis and celiac disease. Accumulating evidence suggests that recognition of modified self-proteins may also be important in type 1 diabetes. Our objective was to identify posttranslationally modified GAD65 peptides, which are recognized by subjects with type 1 d...

BACKGROUND Autoantibodies to GAD65 (anti-GAD65) are present in the sera of 70-80% of patients with type 1 diabetes (T1D), but antibodies to the structurally similar 67 kDa isoform GAD67 are rare. Antibodies to GAD67 may represent a cross-reactive population of anti-GAD65, but this has not been formally tested. METHODOLOGY/PRINCIPAL FINDINGS In this study we examined the frequency, levels and ...

Autoreactive CD4(+) T cells are an essential feature of type 1 diabetes mellitus. We applied single-cell TCR α- and β-chain sequencing to peripheral blood GAD65-specific CD4(+) T cells, and TCR α-chain next-generation sequencing to bulk memory CD4(+) T cells to provide insight into TCR diversity in autoimmune diabetes mellitus. TCRs obtained for 1650 GAD65-specific CD4(+) T cells isolated from ...

OBJECTIVE The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known. METHOD Using polym...

The thalamus may be the critical brain area involved in sensory gating and the relay of respiratory mechanical information to the cerebral cortex for the conscious awareness of breathing. We hypothesized that respiratory mechanical stimuli in the form of tracheal occlusions would modulate the gene expression profile of the thalamus. Specifically, it was reasoned that conditioning to the respira...

Our previous study demonstrated that persistent pain can epigenetically suppress the transcription of Gad2 [encoding glutamic acid decarboxylase 65 (GAD65)] and consequently impair the inhibitory function of GABAergic synapses in central pain-modulating neurons. This contributes to the development of persistent pain sensitization. Histone deacetylase (HDAC) inhibitors increased GAD65 activity c...