Dynamic changes in Ccn3 expression across the limbic forebrain through the mouse estrous cycle and during lactation

Area of Science:

• Neuroendocrinology
• Molecular Neuroscience
• Bone Biology

Background:

• Cellular communication network factor 3 (CCN3), also known as nephroblastoma overexpressed (NOV), is an adipocytokine.
• CCN3 is proposed to be secreted by hypothalamic arcuate nucleus kisspeptin (ARN^KISS) neurons.
• This secretion is hypothesized to protect bone density during lactation.

Purpose of the Study:

• To investigate the expression patterns of Ccn3 transcripts in the mouse forebrain.
• To examine Ccn3 expression in males and females across the estrous cycle and during lactation.
• To determine the co-localization of Ccn3 and Kiss1 transcripts in ARN neurons.

Main Methods:

• RNAscope hybridization was employed to detect Ccn3 mRNA.
• Expression analysis was conducted in male and female mice.
• Specific brain regions, including the hypothalamus, cerebral cortex, hippocampus, and amygdala, were examined.

Main Results:

• Ccn3 transcripts were highly expressed in the cerebral cortex, hippocampus, subthalamic nucleus, and amygdala in both sexes.
• Lower Ccn3 mRNA levels were observed in the female hypothalamus, but not in males.
• A significant 6-fold increase in Ccn3 mRNA-expressing cells was noted in the arcuate and dorsomedial nuclei, and medial amygdala during lactation.
• Approximately 50% of ARN cells expressing Ccn3 during lactation also expressed Kiss1.
• Ccn3 mRNA expression in ARN^KISS neurons increased during proestrus.

Conclusions:

• Multiple limbic brain regions and cell types coordinately up-regulate Ccn3 expression during lactation.
• CCN3 expression in ARN^KISS neurons is dynamic and responsive to reproductive states.
• These findings highlight a potential role for CCN3 in regulating neuroendocrine functions related to reproduction and bone metabolism.