193 | Study of melanin-concentrating hormone (MCH) and glutamatergic systems in the streptozotocin (STZ)-induced Alzheimer’s disease (AD) model in male rats.

Disorders of the Nervous System

Author: Sofía Niño | Email: sofianino1994@gmail.com

Sofía Niño Rivero , Marialuisa de Ceglia , Ana Luisa Gavito , Fernando Rodríguez de Fonseca , Jessika Urbanavicius , Patricia Lagos

1° Unidad Académica de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
2° UGC Salud Mental, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
3° Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable, Ministerio de Educación y Cultura, Montevideo, Uruguay.

MCH is a hypothalamic neuropeptide that regulates memory, although with contradictory effects. In agreement, it has been postulated to be involved in AD neuropathological mechanisms. In this work, we study behavioral and molecular changes in the MCHegic system in the STZ-induced AD model. Considering the impact of AD on the glutamatergic system, we evaluated markers in our model that are poorly studied. Cognitive performance were evaluated in intracerebroventricularly STZ or vehicle administered male rats in the Novel Object Recognition (NOR) at 15, 30, 60, 90 or 120 days post-administration. After that, we evaluated MCH levels in cerebrospinal fluid (CSF) by ELISA and MCH receptor 1 expression (immunofluorescence or western blot) in hippocampus or hypothalamus. Regarding the glutamatergic system, we measured NMDA 2A and 2B receptor subunit in hippocampus. We found that cognitive deficits appeared later, T90 and T120. MCH CSF levels were similar at all the stages studied and MCHR-1 expression at primary cilia of hippocampal neurons or protein levels did not shown differences between STZ and control group. However, in the hypothalamus we found increased MCHR-1 expression at T30, 90 and 120. In terms of the glutamatergic system, 2A subunit were significantly increased at T15 and T60. Meanwhile, 2B levels decreased at the later T120 time point. Our results suggest that in this AD model, MCHergic system is modified at hypothalamus whereas the glutamatergic system at hippocamppus