Faculty Collaboration Database

Disruption of the neuregulin 1 gene in the rat alters HPA axis activity and behavioral responses to environmental stimuli. Physiol Behav 2011 Aug 03;104(2):205-14

Date

11/26/2010

Pubmed ID

21092742

Pubmed Central ID

PMC3081908

DOI

10.1016/j.physbeh.2010.11.015

Scopus ID

2-s2.0-79958799340 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

Exposure to stress can result in an increased risk for psychiatric disorders, especially among genetically predisposed individuals. Neuregulin 1 (NRG1) is a susceptibility gene for schizophrenia and is also associated with psychotic bipolar disorder. In the rat, the neurons of the hypothalamic paraventricular nucleus show strong expression of Nrg1 mRNA. In patients with schizophrenia, a single nucleotide polymorphism in the 5' region of NRG1 interacts with psychosocial stress to affect reactivity to expressed emotion. However, there is virtually no information on the role of NRG1 in hypothalamic-pituitary-adrenal axis function, and whether the protein is expressed in the paraventricular nucleus is unknown. The present studies utilize a unique line of Nrg1 hypomorphic rats (Nrg1(Tn)) generated by gene trapping with the Sleeping Beauty transposon. We first established that the Nrg1(Tn) rats displayed reduced expression of both the mRNA and protein corresponding to the Type II NRG1 isoform. After confirming, using wild type animals, that Type II NRG1 is expressed in the neurocircuitry involved in regulating hypothalamic-pituitary-adrenal axis responses to environmental stimuli, the Nrg1(Tn) rats were then used to test the hypothesis that altered expression of Type II NRG1 disrupts stress regulation and reactivity. In support of this hypothesis, Nrg1(Tn) rats have disrupted basal and acute stress recovery corticosterone secretion, differential changes in expression of glucocorticoid receptors in the pituitary, paraventricular nucleus and hippocampus, and a failure to habituate to an open field. Together, these findings point to NRG1 as a potential novel regulator of neuroendocrine responses to stress as well as behavioral reactivity.

Author List

Taylor SB, Taylor AR, Markham JA, Geurts AM, Kanaskie BZ, Koenig JI

Author

Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Analysis of Variance
Animals
Animals, Newborn
Behavior, Animal
Corticosterone
Environment
Exploratory Behavior
Female
Glucocorticoids
Habituation, Psychophysiologic
Hypothalamo-Hypophyseal System
Male
Maternal Behavior
Mutation
Neuregulin-1
Pituitary-Adrenal System
RNA, Messenger
Radioimmunoassay
Rats
Rats, Inbred F344
Rats, Transgenic
Receptors, Mineralocorticoid
Restraint, Physical