Recent studies of the hippocampus have suggested that a network of genes is associated with the regulation of the GAD₆₇ (GAD1) expression and may play a role in γ-amino butyric acid (GABA) dysfunction in schizophrenia (SZ) and bipolar disorder (BD). To obtain a more detailed understanding of how GAD₆₇ regulation may result in GABAergic dysfunction, we have developed an in vitro model in which G...

The role of Sirtuins in brain function is emerging, yet little is known about SIRT5 in this domain. Our previous work demonstrates that protein kinase C epsilon (PKCε)-induced protection from focal ischemia is lost in SIRT5-/- mice. Thus, metabolic regulation by SIRT5 contributes significantly to ischemic tolerance. The aim of this study was to identify the SIRT5-regulated metabolic pathways in...

Schizophrenia (SZ) is associated with GABA neuron dysfunction in the hippocampus, particularly the stratum oriens of sector CA3/2. A gene expression profile analysis of human postmortem hippocampal tissue followed by a network association analysis had shown a number of genes differentially regulated in SZ, including the epigenetic factors HDAC1 and DAXX. To characterize the contribution of thes...

It is suggested that the maternal transmission of islet autoantibodies increases the risk of autoimmune diabetes in mice. The aim of this study was to determine whether fetal exposure to islet autoantibodies modified the risk of type 1 diabetes in humans. Islet autoantibodies were measured at birth in 720 offspring of mothers with type 1 diabetes. Offspring were prospectively followed for the d...

Stiffness and spasticity are common neurologic symptoms that affect limb movements. We describe a patient who presented with ill-defined stiffness and an exaggerated startle response, who on serial examinations had variable degrees of stiffness and marked hyperreflexia but with plantar flexor signs. Stiff-person syndrome (SPS) was considered when axial stiffness became evident and was confirmed...

Strategies to induce recovery from lesions of the spinal cord have not fully resulted in clinical applications. This is a consequence of a number of impediments that axons encounter when trying to regrow beyond the lesion site, and that intraspinal rearrangements are subjected to. In the present study we evaluated (1) the possibility to improve locomotor recovery after complete transection of t...

OBJECTIVE We evaluated a novel electrochemiluminescent assay for insulin/proinsulin autoantibodies (ECL-IAA) as a new marker of the onset of islet autoimmunity and as a predictor of type 1 diabetes. RESEARCH DESIGN AND METHODS The Diabetes Autoimmunity Study in the Young (DAISY) prospectively follows children at increased genetic risk for development of islet autoimmunity (defined as presence...

Sleep-wake behavior is regulated by a circadian rhythm, homeostatically and by additional mechanisms that determine the timing of slow-wave sleep and rapid eye movement sleep (REMS) episodes. The posterior hypothalamus coordinates the neural and humoral signals with the rest-activity cycle. It contains wake-active neurons, and is a site where stimulation of inhibitory GABAA receptors promotes s...

OBJECTIVES Development of the nervous system in human and most animals is continued after the birth. Critical role of this period in generation and specialization of the neuronal circuits is confirmed in numerous studies. Any pharmacological intervention in this period may result in structural, functional or behavioral abnormalities. In this study, sodium thiopental a GABA mimetic drug was admi...

GAD is a major target of autoimmunity in preclinical type 1 diabetes. Here we examine the maturation of the humoral response to GAD epitopes sequentially from birth to diabetes onset or current follow-up in 29 GAD antibody (GADA)+ offspring of parents with diabetes from the BABYDIAB Study. Antibodies were measured against GAD65, GAD67, and GAD65/67 chimeras by radiobinding assay. In 28 of 29 of...