Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity.
Mol Psychiatry
; 26(6): 2299-2315, 2021 06.
Article
in En
| MEDLINE
| ID: mdl-33432188
ABSTRACT
Previous studies have shown that AgRP neurons in the arcuate nucleus (ARC) respond to energy deficits and play a key role in the control of feeding behavior and metabolism. Here, we demonstrate that chronic unpredictable stress, an animal model of depression, decreases spontaneous firing rates, increases firing irregularity and alters the firing properties of AgRP neurons in both male and female mice. These changes are associated with enhanced inhibitory synaptic transmission and reduced intrinsic neuronal excitability. Chemogenetic inhibition of AgRP neurons increases susceptibility to subthreshold unpredictable stress. Conversely, chemogenetic activation of AgRP neurons completely reverses anhedonic and despair behaviors induced by chronic unpredictable stress. These results indicate that chronic stress induces maladaptive synaptic and intrinsic plasticity, leading to hypoactivity of AgRP neurons and subsequently causing behavioral changes. Our findings suggest that AgRP neurons in the ARC are a key component of neural circuitry involved in mediating depression-related behaviors and that increasing AgRP neuronal activity coule be a novel and effective treatment for depression.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arcuate Nucleus of Hypothalamus
/
Depression
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Psychiatry
Journal subject:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Year:
2021
Document type:
Article
Affiliation country: