Nk3R blockade has sex-divergent effects on memory in mice

Area of Science:

• Neuroscience
• Endocrinology
• Molecular Biology

Background:

• Memory consolidation is crucial for long-term memory formation.
• The neurokinin-3 receptor (Nk3R) and sex hormones influence fear memory consolidation, with opposing effects in males and females.
• The role of Nk3R in other memory types across sexes is unknown.

Purpose of the Study:

• To investigate the effect of systemic Nk3R blockade on memory consolidation using the novel object recognition paradigm.
• To examine the expression of estrogen receptors (ERα, ERβ), androgen receptors (AR), and Nk3R heterodimerization in the medial prefrontal cortex (mPFC) and dorsal hippocampus (DH).

Main Methods:

• Systemic administration of an Nk3R antagonist.
• Novel object recognition test for memory assessment.
• Western blot analysis for receptor expression and heterodimerization in brain regions (mPFC, DH).

Main Results:

• Nk3R antagonism impaired memory consolidation in males but enhanced it in females during proestrus.
• Differential expression of Nk3R, ERα, ERβ, and AR was observed between sexes in the mPFC and DH.
• Evidence of Nk3R heterodimerization with G-protein estrogen receptors in females and G-protein androgen receptors in males was found, suggesting hormone-specific interactions.

Conclusions:

• Sex-specific interactions between Nk3R and sex hormones (estradiol, testosterone) modulate memory consolidation.
• Differential receptor expression and heterodimerization highlight distinct molecular mechanisms in males and females.
• These findings offer new insights into the neurobiological basis of memory consolidation.