RESUMO
Melanocortin-3 receptors (MC3R) have a contextual role in appetite control that is amplified with hypocaloric conditioning. C57BL/6J (B6) mice subjected to hypocaloric feeding schedules (HFS) exhibit compulsive behavioral responses involving food anticipatory activity (FAA) and caloric loading following food access. These homeostatic responses to calorie-poor environs are attenuated in B6 mice in which Mc3r transcription is suppressed by a lox-stop-lox sequence in the 5'UTR (Mc3rTB/TB). Here, we report that optimization of caloric loading in B6 mice subject to HFS, characterized by increased meal size and duration, is not observed in Mc3rTB/TB mice. Analysis of hypothalamic and neuroendocrine responses to HFS throughout the light-dark cycle suggests uncoupling of hypothalamic responses involving appetite-stimulating fasting-responsive hypothalamic neurons expressing agouti-related peptide (AgRP) and neuropeptide Y (Npy). Rescuing Mc3rs expression in Nkx2.1(+ve) neurons is sufficient to restore normal hypothalamic responses to negative energy balance. In addition, Mc3rs expressed in Nkx2.1(+ve) neurons are also sufficient to restore FAA and caloric loading of B6 mice subjected to HFS. In summary, MC3Rs expressed in Nkx2.1(+ve) neurons are sufficient to coordinate hypothalamic response and expression of compulsive behavioral responses involving meal anticipation and consumption of large meals during situations of prolonged negative energy balance.
Assuntos
Proteína Relacionada com Agouti/genética , Metabolismo Energético/genética , Neuropeptídeo Y/genética , Receptor Tipo 3 de Melanocortina/genética , Animais , Apetite/genética , Ingestão de Energia/genética , Homeostase , Hipotálamo/metabolismo , Camundongos , Neurônios/metabolismo , Fotoperíodo , Fator Nuclear 1 de Tireoide/genéticaRESUMO
Accumulating evidence renders the dogma obsolete according to which the structural organization of the brain would remain essentially stable in adulthood, changing only in response to a need for compensatory processes during increasing age and degeneration. It has indeed become clear from investigations on various models that the adult nervous system can adapt to physiological demands by altering reversibly its synaptic circuits. This potential for structural and functional modifications results not only from the plastic properties of neurons but also from the inherent capacity of the glial cellular components to undergo remodeling as well. This is currently known for astrocytes, the major glial cells in brain which are well-recognized as dynamic partners in the mechanisms of synaptic transmission, and for the tanycytes and pituicytes which contribute to the regulation of neurosecretory processes in neurohemal regions of the hypothalamus. Studies on the neuroendocrine hypothalamus, whose role is central in homeostatic regulations, have gained good insights into the spectacular neuronal-glial rearrangements that may subserve functional plasticity in the adult brain. Following pioneering works on the morphological reorganizations taking place in the hypothalamo-neurohypophyseal system under certain physiological conditions such as dehydration and lactation, studies on the gonadotropic system that orchestrates reproductive functions have re-emphasized the dynamic interplay between neurons and glia in brain structural plasticity processes. This review summarizes the major contributions provided by these researches in the field and also addresses the question of the morphological rearrangements that occur on a 24-h basis in the central component of the circadian clock responsible for the temporal aspects of endocrine regulations. Taken together, the reviewed data highlight the close cooperation between neurons and glia in developing strategies for functional adaptation of the brain to the changing conditions of the internal and external environment.