Mice deficient in AKAP13 (BRX) develop compulsive-like behavior and increased body weight
| Autor: | Szu Chi Su, James H. Segars, Charles R. Armstrong, K. Maravet Baig, Irina Burd, Emma Giuliani, Elyse Pettiford, Nils Olsen, Margaret F. Keil, Sunni L. Mumford, Kamaria C. Cayton Vaught, Sinnie Sin Man Ng |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Obsessive-Compulsive Disorder medicine.medical_specialty medicine.drug_class A Kinase Anchor Proteins Estrogen receptor Alpha (ethology) Mice Transgenic Anxiety Biology Article Minor Histocompatibility Antigens 03 medical and health sciences Sex Factors 0302 clinical medicine Internal medicine medicine Animals Guanine Nucleotide Exchange Factors Obesity Behavior Animal General Neuroscience Body Weight Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology Hypothalamus Sex steroid Estrogen Compulsive Behavior Female Analysis of variance Haploinsufficiency 030217 neurology & neurosurgery Hormone |
| Zdroj: | Brain Research Bulletin. 140:72-79 |
| ISSN: | 0361-9230 |
| Popis: | OBJECTIVE: Hormonal contributions to the sex-dependent development of both obsessive-compulsive disorder (OCD) and obesity have been described, but the underlying mechanisms are incompletely understood. A-kinase anchoring protein 13 (AKAP13) significantly augments ligand-dependent activation of estrogen receptors alpha and beta. The hypothalamus and pituitary gland are implicated in the development and exacerbation of OCD and obesity and have strong AKAP13 expression. The AKAP13 localization pattern observed in these key brain regions together with its effects on sex steroid action suggest a potential role for AKAP13 in compulsive-like behaviors. Here we tested the role of AKAP13 in compulsive-like behavior and body weight using an Akap13 haploinsufficient murine model. MATERIALS AND METHODS: Targeted deletion of the Akap13 gene generated haploinsufficient (Akap13+/−) mice in a C57BL6/J genetic background. Established behavioral assays were conducted, video recorded, and scored blindly to assess compulsive-like behavior based on genotype and gender. Tests included: marble-burying, grooming, open-field and elevated plus-maze. Brain and body weights were also obtained. Mean levels of test outcomes were compared using multi-way ANOVA to test for genotype, sex, genotype*sex, and genotype*sex*age interaction effects with Bonferroni adjustment for multiple comparisons, to further explain any significant interactions. RESULTS: The marble-burying and grooming assays revealed significant sex-dependent increases in perseverative, compulsive-like behaviors in female Akap13 haploinsufficient mice compared to female wild type (WT) mice by demonstrating increased marble-burying activity (p=0.0025) and a trend towards increased grooming behavior (p=0.06). Male Akap13 haploinsufficient mice exhibited no behavioral changes (p>0.05). Elevated plus-maze and open-field test results showed no overt anxiety-like behavior in Akap13 haploinsufficient mice irrespective of sex (p>0.05, both). No differences in brain weight were found in Akap13 haploinsufficient mice compared to WT mice (p>0.05). However, female Akap13 haploinsufficient mice weighed more than female WT mice in the 4 to 0.05) at any age range examined. CONCLUSION: Akap13 haploinsufficiency led to sex-dependent, compulsive-like behavioral changes in a murine model. Interestingly, Akap13 haploinsufficiency also led to a sex-dependent increase in body weight. These results revealed a requirement for AKAP13 in murine behavior, particularly in female mice, and is the first report of AKAP13 involvement in murine behavior. Future studies may show AKAP13 involvement in the pathophysiology of OCD in female humans and may contribute to a better understanding of the role of AKAP13 and sex hormones in the development and exacerbation of OCD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect