PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse

Pituitary adenylate cyclase activating polypeptide (PACAP, ) is a neuromodulator implicated in anxiety, metabolism and reproductive behavior. PACAP global knockout mice have decreased fertility and PACAP modulates LH release. However, its source and role at the hypothalamic level remain unknown. We...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2018-06, Vol.7
Main Authors: Ross, Rachel A, Leon, Silvia, Madara, Joseph C, Schafer, Danielle, Fergani, Chrysanthi, Maguire, Caroline A, Verstegen, Anne Mj, Brengle, Emily, Kong, Dong, Herbison, Allan E, Kaiser, Ursula B, Lowell, Bradford B, Navarro, Victor M
Format: Article
Language:English
Subjects:
Animals
Brain
Female
Gonadotropin-Releasing Hormone - metabolism
hypothalamus
kisspeptin
Kisspeptins - genetics
Kisspeptins - metabolism
Leptin
Male
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Neural circuitry
Neurons
Neurons - cytology
Neurons - metabolism
Neuroscience
PACAP
Physiological aspects
Pituitary Adenylate Cyclase-Activating Polypeptide - genetics
Pituitary Adenylate Cyclase-Activating Polypeptide - metabolism
Polypeptides
Receptors, Leptin - genetics
Receptors, Leptin - metabolism
reproduction
Reproduction - genetics
Reproduction - physiology
Sex Factors
Sexual Maturation - genetics
Ventromedial Hypothalamic Nucleus - cytology
Ventromedial Hypothalamic Nucleus - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pituitary adenylate cyclase activating polypeptide (PACAP, ) is a neuromodulator implicated in anxiety, metabolism and reproductive behavior. PACAP global knockout mice have decreased fertility and PACAP modulates LH release. However, its source and role at the hypothalamic level remain unknown. We demonstrate that PACAP-expressing neurons of the ventral premamillary nucleus of the hypothalamus (PMV ) project to, and make direct contact with, kisspeptin neurons in the arcuate and AVPV/PeN nuclei and a subset of these neurons respond to PACAP exposure. Targeted deletion of PACAP from the PMV through stereotaxic virally mediated cre- injection or genetic cross to LepR-i-cre mice with mice led to delayed puberty onset and impaired reproductive function in female, but not male, mice. We propose a new role for PACAP-expressing neurons in the PMV in the relay of nutritional state information to regulate GnRH release by modulating the activity of kisspeptin neurons, thereby regulating reproduction in female mice.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.35960