Immunometabolic Changes in Glia - A Potential Role in the Pathophysiology of Obesity and Diabetes.

Chronic low-grade inflammation is a feature of the pathophysiology of obesity and diabetes in the CNS as well as peripheral tissues. Glial cells are critical mediators of the response to inflammation in the brain. Key features of glia include their metabolic flexibility, sensitivity to changes in the CNS microenvironment, and ability to rapidly adapt their function accordingly. They are specialised cells which cooperate to promote and preserve neuronal health, playing important roles in regulating the activity of neuronal networks across the brain during different life stages. Increasing evidence points to a role of glia, most notably astrocytes and microglia, in the systemic regulation of energy and glucose homeostasis in the course of normal physiological control and during disease. Inflammation is an energetically expensive process that requires adaptive changes in cellular metabolism and, in turn, metabolic intermediates can also have immunomodulatory actions. Such "immunometabolic" changes in peripheral immune cells have been implicated in contributing to disease pathology in obesity and diabetes. This review will discuss the evidence for a role of immunometabolic changes in glial cells in the systemic regulation of energy and glucose homeostasis, and how this changes in the context of obesity and diabetes.

Sex-associated differences in excitability within the bed nucleus of the stria terminalis are reflective of cell-type.

The bed nucleus of the stria terminalis (BNST) is a sexually dimorphic brain region which plays a key role in stress, anxiety, and anxiety-related disorders. Human females have an increased susceptibility to anxiety-related disorders, however the physiological basis of this is not fully understood. Here we examined the effect of the oestrous cycle and sex on the electrophysiological properties of Type I and Type II cells in the anterolateral area of the BNST (BNSTALG) in unstressed animals. There was no significant effect of oestrous cycle on any of the parameters examined in either cell type. Compared to males, the female cohort had lower capacitance in Type I cells while having a higher capacitance in Type II cells. Type II cells also displayed decreased excitability in the female cohort. In order to confirm the effect of these populations on stress and anxiety, a correlation with behaviour on the elevated zero maze was carried out. We observed that increased excitability in Type II neurons correlated with a decrease in anxiety-like behaviour. These sex-specific differences in excitability may contribute to altered susceptibility to anxiety-related disorders.

Aging-Associated Changes to Intrinsic Neuronal Excitability in the Bed Nucleus of the Stria Terminalis Is Cell Type-Dependent.

Intrinsic neuronal excitability has been reported to change during normal aging. The bed nucleus of the stria terminalis (BNST), a limbic forebrain structure, is involved in fear, stress and anxiety; behavioral features that exhibit age-dependent properties. To examine the effect of aging on intrinsic neuronal properties in BNST we compared patch clamp recordings from cohorts of female mice at two ages, 3-4 months (Young) and 29-30 months (Aged) focusing on 2 types of BNST neurons. Aged Type I neurons exhibited a hyperpolarized resting membrane potential (RMP) of circa -80 mV compared to circa -70 mV in the Young. A key finding in this study is a hyper-excitability of Type II neurons with age reflected in an increase in firing frequency in response to depolarizing current injections; activation of Type II neurons is believed to dampen anxiety like responses. Such age-related changes in intrinsic neurophysiological function are likely to modulate how the limbic system, acting via BNST, shapes function in the HPA-axis.