Abstract
The amygdala is an important center of fear learning and memory and plays a critical role in regulating stress disorders. Previous studies have shown that changes in the amygdala caused by stress are an important cause of mental disorders including anxiety, but the specific mechanism remains unclear. Therefore, the purpose of this study was to investigate whether mental disorders induced by stress are related to γ-aminobutyric acid (GABA)ergic neuron damage in the basolateral amygdala (BLA) and whether endoplasmic reticulum stress (ERS) is involved in the injury process. Rat models of different durations of stress were established by restraint and forced ice-water swimming. Behavioral tests and high-performance liquid chromatography (HPLC) were used to detect anxiety in rats and changes in neurotransmitter levels in the BLA. Morphological approaches and microscopy-based multicolor tissue cytometry (MMTC) were used to detect the damage-induced changes in GABAergic neurons in the BLA. Immunofluorescence double labeling was used to detect the expression of ERS-related proteins before and after the inhibition of protein kinase R-like endoplasmic reticulum kinase (PERK) pathway. Stress resulted in damage to GABAergic neurons in the BLA, decreased GABA and increased glutamic acid (GLU) levels, perturbation of the excitation/inhibition (E/I) ratio in the BLA, and obvious anxiety disorders in rats. Moreover, ERS-mediated GABAergic neuron injury was an important cause of neurotransmitter level changes in the BLA. These results suggested that ERS-mediated GABAergic neuron injury in the BLA may be an important cause of stress-induced mental disorders.
Highlights
Stress involves a series of neuroendocrine, physiological and pathological reactions that occur when the body is stimulated by internal and external factors (McEwen, 2007)
Stress is essentially a defensive adaptive response used by the body to maintain homeostasis of the internal environment through neuroendocrine regulation to better adapt to changes in external stimuli
The amygdala is an important part of the limbic system and plays a critical role in stress-induced mental disorders (LeDoux, 2000; Davis and Whalen, 2001)
Summary
Stress involves a series of neuroendocrine, physiological and pathological reactions that occur when the body is stimulated by internal and external factors (McEwen, 2007). The amygdala is a key brain region for the acquisition and processing of learned fear associations, and plays a critical role in regulating stress-induced disorders, including anxiety disorders (LeDoux, 2000; Davis and Whalen, 2001). Patients with stress-induced anxiety disorder have abnormally increased activity levels in the BLA (Etkin et al, 2009).
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