Neuroinflammation attenuation effects by celastrol and PDIA3 in the amygdala, hippocampus and dorsal raphe nucleus of obese mice

• The expression of PDIA3 is differentially disturbed in the BLA, CA3 and DRN of the obesity-depression comorbid mice. • Celastrol covalently bind and differentially modulate the expression of PDIA3 in above brain nuclei. • PDIA3 expressed in BLA and CA3 alleviate the comorbid conditions, whereas in DRN deteriorate obesity. • In BLA and CA3, overexpressed PDIA3 reshape the activated amoeboid microglia into the ramified quiescent ones. • In DRN, overexpressed PDIA3 may influence 5-HTergic neurons.