Obesogenic Diet-Induced Neuroinflammation: A Pathological Link between Hedonic and Homeostatic Control of Food Intake.

Obesity-induced neuroinflammation is a chronic aseptic central nervous system inflammation that presents systemic characteristics associated with increased pro-inflammatory cytokines such as interleukin 1 beta (IL-1ß) and interleukin 18 (IL-18) and the presence of microglia and reactive astrogliosis as well as the activation of the NLRP3 inflammasome. The obesity pandemic is associated with lifestyle changes, including an excessive intake of obesogenic foods and decreased physical activity. Brain areas such as the lateral hypothalamus (LH), lateral septum (LS), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been implicated in the homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. In this context, a chronic lipid intake triggers neuroinflammation in several brain regions such as the hypothalamus, hippocampus, and amygdala. This review aims to present the background defining the significant impact of neuroinflammation and how this, when induced by an obesogenic diet, can affect feeding control, triggering metabolic and neurological alterations.

Gliotransmission: A Novel Target for the Development of Antiseizure Drugs.

For more than a century, epilepsy has remained an incapacitating neurological disorder with a high incidence worldwide. Mesial temporal lobe epilepsy (TLE) is a common type of epilepsy without an effective pharmacological treatment. An increase in excitability and hypersynchrony of electrical neuronal activity during development are typically associated with an excitatory/inhibitory imbalance in the neuronal network. Astrocytes release gliotransmitters, which can regulate neuronal excitability and synaptic transmission; therefore, the classical neurocentric vision of the cellular basis of epileptogenesis has begun to change. Growing evidence suggests that the key contribution of astrocyte-to-neuron signaling in the mechanisms underlies the initiation, propagation, and recurrence of seizure activity. The aim of this review was to summarize current evidence obtained from experimental models that suggest how alterations in astroglial modulation of synaptic transmission and neuronal activity contribute to the development of this brain disease. In this article, we will summarize the main pharmacological, Ca2+-imaging, and electrophysiological findings in the gliotransmitter-mediated modulation of neuronal activity and their possible regulation as a novel cellular target for the development of pharmacological strategies for treating refractory epilepsies.