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Monoamine Oxidase A is Required for Rapid Dendritic Remodeling in Response to Stress
Sean C Godar1, Marco Bortolato1, Sarah E Richards1
1Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA (Drs Godar, Chen, and Shih and Mr Li); Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA (Dr Shih); Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS (Drs Godar and Bortolato); Consortium for Translational Research on Aggression and Drug Abuse (ConTRADA), University of Kansas, Lawrence, KS, (Drs Godar and Bortolato); Department of Psychological & Brain Sciences and Program in Neuroscience, Indiana University, Bloomington, IN (Ms Richards and Dr Wellman).
Background:
Acute stress triggers transient alterations in the synaptic release and metabolism of brain monoamine neurotransmitters. These rapid changes are essential to activate neuroplastic processes aimed at the appraisal of the stressor and enactment of commensurate defensive behaviors. Threat evaluation has been recently associated with the dendritic morphology of pyramidal cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA); thus, we examined the rapid effects of restraint stress on anxiety-like behavior and dendritic morphology in the BLA and OFC of mice. Furthermore, we tested whether these processes may be affected by deficiency of monoamine oxidase A (MAO-A), the primary enzyme catalyzing monoamine metabolism.
Methods:
Following a short-term (1-4h) restraint schedule, MAO-A knockout (KO) and wild-type (WT) mice were sacrificed, and histological analyses of dendrites in pyramidal neurons of the BLA and OFC of the animals were performed. Anxiety-like behaviors were examined in a separate cohort of animals subjected to the same experimental conditions.
Results:
In WT mice, short-term restraint stress significantly enhanced anxiety-like responses, as well as a time-dependent proliferation of apical (but not basilar) dendrites of the OFC neurons; conversely, a retraction in BLA dendrites was observed. None of these behavioral and morphological changes were observed in MAO-A KO mice.
Conclusions:
These findings suggest that acute stress induces anxiety-like responses by affecting rapid dendritic remodeling in the pyramidal cells of OFC and BLA; furthermore, our data show that MAO-A and monoamine metabolism are required for these phenomena.
