Prolactin-induced and neuronal activation in the brain of mother mice

Brain Struct Funct. 2018 Sep;223(7):3229-3250. doi: 10.1007/s00429-018-1686-1. Epub 2018 May 25.

Abstract

Nursing has important consequences on mothers. To separate the prolactin-mediated and the neuronally-mediated actions of nursing, neurons directly affected by prolactin were visualized using pSTAT5 immunohistochemistry in relation to Fos-expressing neurons in suckled mother mice. In response to pup exposure following 22-h pup deprivation, we found a markedly elevated number of pSTAT5-containing neurons in several brain regions, including the lateral septum, medial amygdaloid nucleus, subparafascicular area, caudal periaqueductal gray, dorsal raphe, lateral parabrachial nucleus, nucleus of the solitary tract, and the periventricular, medial preoptic, paraventricular, arcuate and ventromedial nuclei of the hypothalamus. Pup exposure also induced Fos expression in all of these brain regions except the arcuate and ventromedial hypothalamic nuclei. Bromocriptine treatment known to reduce prolactin levels eliminated pSTAT5 from most brain regions while it did not affect Fos activation following suckling. The degree of colocalization for pSTAT5 and Fos ranged from 8 to 80% in the different brain regions suggesting that most neurons responding to pup exposure in mother mice are driven either by prolactin or direct neuronal input from the pups, while the number of neurons affected by both types of inputs depends on the examined brain area. In addition, both pSTAT5 and Fos were also double-labeled with estrogen receptor alpha (ERα) in mother mice, which revealed a very high degree of colocalization between pSTAT5 and ERα with much less potential interaction between Fos- and ERα-containing neurons suggesting that estrogen-sensitive neurons are more likely to be affected by prolactin than by direct neuronal activation.

Keywords: Bromocriptine; Estrogen receptor; Hypothalamus; Lactation; Mice dam; Postpartum period; Suckling; pSTAT5.

MeSH terms

  • Animals
  • Animals, Suckling
  • Behavior, Animal
  • Brain / drug effects
  • Brain / metabolism*
  • Bromocriptine / pharmacology
  • Estrogen Receptor alpha / metabolism
  • Female
  • Hormone Antagonists / pharmacology
  • Lactation / metabolism*
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism*
  • Phosphorylation
  • Prolactin / metabolism*
  • Proto-Oncogene Proteins c-fos / metabolism*
  • STAT5 Transcription Factor / metabolism*

Substances

  • Estrogen Receptor alpha
  • Hormone Antagonists
  • Proto-Oncogene Proteins c-fos
  • STAT5 Transcription Factor
  • Bromocriptine
  • Prolactin