CGRP overexpression does not alter depression-like behavior in mice.

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• Calcitonin gene-related peptide (CGRP) is a vasodilator involved in pain and inflammation, notably studied in migraines.
• The role of CGRP overexpression in depressive-like behaviors is not well understood.

Purpose of the Study:

• To investigate the effects of CGRP overexpression on depressive-like behaviors in mice.
• To analyze the impact of stress on CGRP-overexpressing mice and relevant molecular pathways.

Main Methods:

• Behavioral tests (social interaction, open field, sucrose preference) were used to assess stress and depressive-like behaviors in CGRP transgenic (Tg) mice.
• mRNA and protein analyses were conducted on hippocampal brain-derived neurotrophic factor (BDNF), phosphorylated Akt, mTOR, and p70S6K.

Main Results:

• CGRP Tg mice initially showed stress resistance with increased BDNF mRNA but normal social interaction.
• After 15-day social defeat stress, CGRP Tg mice exhibited depressive-like phenotypes, including social avoidance and reduced sucrose preference.
• Stress exposure decreased hippocampal p-Akt, p-mTOR, and p-p70S6K levels in CGRP Tg mice, while BDNF levels remained unchanged.

Conclusions:

• CGRP-overexpressing mice demonstrate normal sensitivity to social defeat stress.
• Stress induces depressive-like behaviors in CGRP Tg mice, linked to down-regulation of the hippocampal Akt/mTOR/p70S6K signaling pathways.