Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperEffects of chronic immobilization stress on anxiety-like behavior and basolateral amygdala morphology in Fmr1 knockout mice
Highlights
▶Chronic stress (CS) on anxiety and amygdala dendrites in WT and Fmr1 KO mice. ▶Control Fmr1 KO mice had reduced dendritic arbors and elevated spine densities. ▶ACTH and CORT increased in both genotypes in response to spatial novelty after CS. ▶CS increased anxiety and dendritic branching in WT but not in Fmr1 KO mice. ▶Following CS, spine density increased in WT but decreased in Fmr1 KO mice.
Section snippets
Animals
Male WT and Fmr1 KO offspring were generated by FVB/NJ-Fmr1tm1Cgr breeding pairs (heterozygous females and WT males). We studied male WT and Fmr1 KO mice at 96±1 days of age. Mice with no previous exposure to these or any other stressful conditions were singly housed, beginning one week before the study. Four groups of mice were studied: WT-unstressed control (WT-US) (n=24), Fmr1 KO-US control (n=24), WT-CS (n=19), Fmr1 KO-CS (n=20). All mice were housed in a central facility and maintained
Effects of CS on body weight
We monitored body weight during the 10 days of CS (Fig. 1A). Body weight tended to decrease on Day 3 of CS in both genotypes and continued to decrease in Fmr1 KO mice, while leveling off in WT. The genotype×condition×day of stress interaction was statistically significant (F(4.1,316.8)=2.401, P=0.048). At each time point, we tested for differences between four pairs of groups by means of post hoc t-tests. Results indicate that in US mice, body weights were higher in Fmr1 KO mice compared with
Discussion
The central finding of this study is that stress-induced remodeling of dendritic arbors in murine amygdala is altered in the absence of FMRP. Moreover, Fmr1 KO mice fail to show the increased anxiety induced by CS in rodents. Our findings indicate that these differences in response to CS between WT and Fmr1 KO mice are not the result of a deficiency at the level of circulating stress hormones, because hormone responses are intact in the Fmr1 KO mouse. Results of our study indicate that
Conclusions
Long-term adaptive changes are essential for optimal function of the nervous system. They endow the nervous system with the ability to respond to the environment and make adjustments important for survival. In WT mice, such changes occur in response to CS and are manifest as increased anxiety-like behavior and structural remodeling in the amygdala. Fmr1 KO mice appear to lack this capacity to respond to CS in BLA at least in the time frame that we have studied. Our findings indicate that this
Acknowledgments
We thank Dr. Zhong-Hua Liu for help with the statistical analyses. The research was supported by the Intramural Research Program of the NIMH, NIH and the Fragile X Research Foundation.
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