Glipr1-expressing VMN neurons role in stress-induced hyperglycaemia – UROP Spring Symposium 2024

Glipr1-expressing VMN neurons role in stress-induced hyperglycaemia

Carla Burton

Pronouns: she/her

Research Mentor(s): Alison Affinati
Research Mentor School/College/Department: Internal Medicine / Medicine
Program:
Authors: Carla Burton, Amanda Mancuso, Jennifer Wloszek, Jiaao Su, Alison Affinati
Session: Session 1: 9:00 am – 9:50 am
Poster: 2

Abstract

The Ventromedial Nucleus of the Hypothalamus (VMN) plays a crucial role in homeostatic regulations, such as glucose mobilization and energy homeostasis, and defensive behaviors including fear and aggression. However, the neuronal mechanisms behind the distinct functions of the VMN are unclear due to the heterogeneity of the region. To identify new VMN subpopulations, we performed single-cell RNA-sequencing and identified a previously unstudied group of VMN neurons marked by Glipr1 (VMN-Glipr1) expression. Preliminary experiments suggest (VMN-Glipr1) are not imperative to baseline metabolism including body weight and blood glucose, however there is a muted glycemic response to physical stressors, such as restraint. Thus, we hypothesize that Glipr1-expressing neurons are specifically involved in the glycemic stress response through the hypothalamic-pituitary- adrenal (HPA) axis and corticosterone production. To test this, we silenced neurons expressing Glipr1-cre using a cre-dependent tetanus toxin virus that prevents neurotransmitter release, therefore preventing downstream neuronal communication. Thus far, we replicated our preliminary data that VMN-Glipr1 neuron silencing through tetanus toxin expression mutes glucose mobilization under restraint stress and novel environment, while not altering baseline and fasting glucose. Future experiments will focus on investigating distinct stressors and their relevance in this mutes glycemic response (i.e. metabolic stressors vs physical) and hormonal analysis to elucidate their importance on corticosterone production. Through investigating the functional significance of the VMN-Glipr1 neurons, we will advance our understanding of the glycemic responses to stress coordinated by the VMN.

Biomedical Sciences, Interdisciplinary, Natural/Life Sciences

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