Kisspeptin fiber and receptor distribution analysis suggests its potential role in central sensorial processing and behavioral state control

Abstract

Kisspeptin (Kp) is a neuropeptide well-established as the master regulator of the mammalian reproductive axis. However, information on Kp neuronal chemotype and distribution, especially in extra-hypothalamic brain regions, is incomplete, and has limited understanding of how Kp neurons function to affect behavior beyond direct effects on LH-RH release and activation of the hypothalamo-pituitary gonadal (HPG) axis. We therefore examined the chemotype (molecular signature) and fiber distribution of Kp neurons throughout the brain in mice and rat. Serial immunohistochemical sampling employing dual in situ hybridization with mRNA probes for kisspeptin and VGAT, VGLUT2, neurokinin, dynorphin, estrogen receptors, and androgen receptor was used for neuroanatomical analysis. Five distinct types of Kp-expressing cell populations distinguished by molecular signature were identified. One hundred sixteen brain regions were observed to contain Kp fibers and terminals, and eighty-one of these were extra-hypothalamic regions closely involved in central sensory processing and behavioral state control. This study provides an anatomical basis for further hypothesis generation and testing for the role of Kp in a wider scope of brain function than previously envisaged.