RLN3/RXFP3 Signaling in the PVN Inhibits Magnocellular Neurons via M-like Current Activation and Contributes to Binge...

Area of Science:

• Neuroscience
• Endocrinology
• Behavioral Science

Background:

• Binge-eating disorder (BED) is the most prevalent eating disorder, disproportionately affecting women.
• Neuropeptides, including relaxin-3 (RLN3), regulate feeding behavior.
• RLN3 exerts orexigenic effects through the relaxin-family peptide-3 receptor (RXFP3).

Purpose of the Study:

• To elucidate the mechanism of RLN3's orexigenic action in the paraventricular nucleus (PVN).
• To investigate the role of RLN3/RXFP3 signaling in binge-eating behavior.
• To characterize sex differences in RLN3 innervation of the PVN.

Main Methods:

• Electrophysiological recordings in male and female rats.
• Immunohistochemistry to assess RLN3 fiber density.
• Pharmacological blockade of RXFP3 in a rat model of binge-eating.

Main Results:

• RLN3 inhibits oxytocin and vasopressin-synthesizing magnocellular neurosecretory cells in the PVN via RXFP3.
• This inhibition is dependent on M-like potassium conductance.
• Females exhibit higher intra- and peri-PVN RLN3 fiber density compared to males.
• RXFP3 blockade in the PVN attenuated binge-eating behavior in female rats.

Conclusions:

• Hypothalamic RLN3/RXFP3 signaling directly regulates binge-eating behavior.
• The findings identify specific ionic mechanisms underlying RLN3's action in the PVN.
• Sex differences in PVN innervation may contribute to BED prevalence disparities.
• RXFP3 represents a potential therapeutic target for binge-eating disorders.