Assessment of the Role of the Glutamatergic System in the Activation of Melanin-Concentrating Hormone Neurons

The hypothalamus is the part of the central nervous system that contains many neuropeptide and neurotransmitter systems. It functions as an integrative center for peripheral and central signals that control appetite and regulate energy homeostasis. Neurons located in various nuclei of the hypothalamus regulate feeding behavior with the many different hormones and peptides they synthesize. While some of these molecules have orexigenic effects that stimulate food intake, others have anorexigenic effects that suppress food intake. One orexigenic peptide is melanin-concentrating hormone (MCH). The mammalian melanin-concentrating hormone is a nineteen-amino acid neuropeptide produced in the lateral hypothalamic area (LHA) and incerto-hypothalamic area (IHA) in the brain and exerts its orexigenic effects through MCHR1 receptors. In our study, we investigated the relationship between the glutamatergic system and MCH neurons histologically. In the experiments, double immunohistochemical labeling with anti-MCH and anti-pCREB antibodies was performed on sections from rat brains injected with glutamate agonists and antagonists. CREB phosphorylation (pCREB) was used as a marker of neuronal activation in the experiments. In male rats, an increased proportion of MCH neurons expressing pCREB was observed in the lateral hypothalamic nucleus after injection of all three agonists. Applying the specific antagonist before injections of all three agonists led to a statistically significant decrease in the number of activated MCH neurons. This study shows that intracellular pathways that require p-CREB protein expression are used to activate MCH neurons. Additionally, for the first time in the literature, the presence of phosphorylated CREB protein in MCH neurons was determined. New information has been added to the literature on glutamatergic regulation of MCH neurons.