Glutamate mediated signaling in the pathophysiology of autism spectrum disorders.

Autism spectrum disorder (ASD) is a childhood neurodevelopmental disorder. During fetal and neonatal brain development, the cues for neurodevelopment are regulated in a well orchestrated manner. Generally, neurotransmitters play a major role in the formation of central nervous system (CNS) and peripheral nervous system (PNS). Glutamate, the excitatory neurotransmitter actively participates in various neurodevelopmental processes through complex regulatory events. Excitatory neurotransmitter signaling via glutamate receptors modulates cognitive functions such as memory and learning, which are usually impaired in ASD. Therefore, glutamate and its regulatory molecules are considered as potential targets for these disorders. Pharmacological, biochemical and behavioral studies reveal possible involvement of glutamatergic system in ASD pathology. An abnormal increase in electrical activity resulting from excessive glutamate signaling causes prolonged alterations in behavior, as commonly seen in ASDs. On the contrary, reports on animal models of hypoglutamatergia demonstrate phenotypes that overlap with features seen in autism. So controversies prevail whether to regard autism as hyper- or hypo-glutamatergic disorder. This paper reviews the role of glutamate and its regulatory proteins such as different receptors, transporters and metabolizing enzymes in the pathophysiology of ASD based on evidences gathered through multidisciplinary approaches. All these information raise the possibility of exploiting glutamatergic neurotransmitter system for future therapeutic interventions for ASD.

Response of melatonin receptor MT1 in spleen of a tropical Indian rodent, Funambulus pennanti, to natural solar insolation and different photoperiodic conditions.

We analyzed the effect of natural solar insolation and artificial photoperiodic conditions on melatonin MT1 receptor expression of a tropical rodent, Funambulus pennanti. Melatonin mediates reproductive and circadian responses and regulates the production of a large number of cytokines, including interleukin-2 (IL-2), via modulation of MT1 receptor expression. Maximum pineal activity, resulting in high melatonin level, low melatonin receptor expression, and increased splenic mass, was noted in the winter months, while an opposite effect was noted during the summer months. Further, constant light exposure mimicked an "enhanced summer"-like condition with significant hyposplenia, and an opposite effect was observed with constant dark exposure with significant splenomegaly in F. pennanti. In the annual study, a slight increase in melatonin level was noted during the monsoon period, when the duration of photoperiod was the same but the amount of solar insolation and direct radiation decreased. The present study found that not only the duration of natural sunlight (i.e., photoperiod) but the intensity of sunlight expressed by solar insolation affects the circulatory level of melatonin and melatonin receptor expression in this wild tropical rodent. An increase in the circulatory level of melatonin induced a decrease in its receptor subtype MT1 expression in splenic cells, both at the transcriptional and translational levels, thus reflecting autoregulatory down-regulation of melatonin receptors. Therefore, in our animal model, F. pennanti melatonin may be suggested as a molecular messenger of photoperiodic signals (duration and intensity) directly acting via MT1 receptor regulation to adapt the immune system of animals residing in the tropical zone.