Faculty Collaboration Database

Adverse early life environment induces anxiety-like behavior and increases expression of FKBP5 mRNA splice variants in mouse brain. Physiol Genomics 2018 Nov 01;50(11):973-981

Date

09/22/2018

Pubmed ID

30240345

DOI

10.1152/physiolgenomics.00054.2018

Scopus ID

2-s2.0-85060294084 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

Adverse early life environment (AELE) predisposes adult offspring toward anxiety disorders. Anxiety disorders are associated with prenatal injuries in key regions of the brain including prefrontal cortex (PFC), hippocampus (HP), and hypothalamus (HT). Injuries in these brain regions result in an impaired hypothalamus-pituitary-adrenal axis (HPA axis) and stress response. An important regulator of the stress response is FK506-binding protein 5 (FKBP5). FKBP5 is a cochaperone of the glucocorticoid receptor (GR) and inhibits GR-mediated regulatory feed-back on the HPA axis in response to stress. Human studies have shown that polymorphisms of FKBP5 are associated with higher FKBP5 levels. Increased FKBP5 leads to GR resistance and impaired negative feedback, which is associated with anxiety disorders. FKBP5 and its mRNA splice variants in the aforementioned brain regions have not been reported. We hypothesized that AELE will increase expression of FKBP5 and its mRNA splice variants in PFC, HP, and HT as well as increase anxiety in adult mice. AELE increased expression of FKBP5 and its mRNA variants in PFC, HP and HT at postnatal day 21. Additionally, AELE caused anxiety and increased GR abundance in association with these changes in FKBP5 expression. We speculate that these changes in FKBP5 mRNA variants affect HPA axis function and contributes to subsequent anxiety-like behavior later in life in AELE mice.

Author List

Ke X, Fu Q, Majnik A, Cohen S, Liu Q, Lane R

Author

Susan Cohen MD Associate Professor in the Pediatrics department at Medical College of Wisconsin

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

Animals
Animals, Newborn
Anxiety
Behavior, Animal
Body Weight
Brain
Corticosterone
Female
Hypothalamo-Hypophyseal System
Male
Mice, Inbred C57BL
Microglia
Pituitary-Adrenal System
Pregnancy
Protein Isoforms
RNA, Messenger
Receptors, Glucocorticoid
Stress, Psychological
Tacrolimus Binding Proteins