Characterization of the temporal expression profile of clock genes and thermogenic pathway in the brown adipose tissue of glaucomatous mice.

• Grant number: 23/14439-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Nathália de Carvalho Magalhães Moraes Figueira Borges
• Grantee: Paloma Roberto Alves
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 17/26651-9 - Glaucoma as a model of temporal information disruption: impact on the metabolism, AP.JP

Abstract

Glaucoma is a progressive optic neuropathy caused by the death of retinal ganglion cells (RGCs) and results in functional impairment, characterized by vision loss. In addition to RGCs being related to the image-forming process, they project to non-image-forming areas in the central nervous system, such as the suprachiasmatic hypothalamic nucleus (SCN, known as the central biological clock). This retino-hypothalamic projection is responsible for synchronizing biological rhythms with environmental light-dark (LD) cycles. Therefore, the death of RGCs induced by glaucoma leads to a reduced detection of photic input and, consequently, a failure in the synchronization mechanism of the endogenous circadian rhythm generated by the SCN. At the heart of this generation are the clock genes, which are the biological tools capable of marking time through a complex biochemical mechanism. In addition to the circadian pacemaker located in the SCN, there are oscillators in peripheral tissues. However, the SCN contributes to the phase synchronization of other clocks, as the absence of the central clock results in a loss of synchrony among peripheral clocks. Results from our laboratory demonstrate that animals with glaucoma exhibit impairment of the central clock's molecular mechanism and a reduction in the amplitude of locomotor activity (a behavioral parameter under the control of the central clock). Furthermore, glaucomatous mice exhibit lower body weight compared to healthy animals of the same age.Using indirect calorimetry assays, we observed that glaucomatous mice, when exposed to cold environmental conditions (10 °C), exhibit a higher rate of exhaled CO2, while the consumption of O2 remains unchanged. Interestingly, glaucomatous animals show a higher prevalence of brown adipocytes compared to the healthy group, which predominantly consists of white adipocytes. This morphological characteristic suggested a functional alteration, as thermal imaging revealed increased heat production in the brown adipose tissue (BAT) of glaucomatous animals. Therefore, we hypothesize that glaucoma may exert effects on the thermogenic activity of BAT. Thus, with this project, we aim to assess the molecular components of the BAT thermogenic pathway, as well as the temporal profile of clock genes in healthy and glaucomatous animals. We will use a spontaneous glaucoma animal model and evaluate the temporal gene expression through real-time PCR for clock genes and the thermogenic pathway in BAT. With the quantitative gene expression results in hand, we will conduct circadian analysis to measure rhythmic parameters.