Abstract
Postpartum depression (PPD) is associated with mood disorders and elevated inflammation. Studies have evidenced the activation/inhibition of autophagy and excessive activation of microglia to have a close relationship with depression. C57 and microglia-specific autophagy-deficient mice (Cx3Cr1Cre/+ATG5loxp/loxp) were employed to establish the chronic unpredicted mild stress depression mice model from embryonic day 7 (E7) to embryonic day 16 (E16). Fluoxetine was administered for 3 weeks (commencing from 1 week after birth). Behavioral tests (open field, forced swimming, and sucrose preference tests) were implemented. Western blot and immunofluorescence staining were employed to assess the brain-derived neurotrophic factor (BDNF) expression level, autophagy-associated proteins, and inflammatory factors. Depressive behavior was reversed following fluoxetine treatment; this was evidenced via open field, sucrose preference, and forced swimming tests. Both BDNF and autophagy-associated proteins (ATG5, Beclin-1, and LC3II) were upregulated following fluoxetine treatment. Inflammatory factors including nuclear factor kappa B and inducible nitric oxide synthase were reduced while anti-inflammatory factor interleukin-10 (IL-10) was increased after fluoxetine treatment. Microglia-specific autophagy-deficient mice (Cx3Cr1Cre/+ATG5loxp/loxp) showed a curtailed autophagy level, higher inflammatory level, and reduced BDNF expression when compared with C57 mice. Autophagy inhibition in microglia contributes to inflammation, which further instigates PPD. Fluoxetine might mediate its antidepressant effect in PPD through the autophagic pathway while upregulating BDNF expression. In view of this, regulating BDNF in microglia is a potential novel therapy target for PPD.
Highlights
Postpartum depression (PPD) is often accompanied by extreme sadness and hopelessness, low energy, anxiety, crying episodes, irritability, and infanticide [1, 2]
Since the role of autophagy in PPD pathogenesis is ambiguous, this study investigates whether the inhibition of autophagy in microglia arouses inflammation, further influencing the usage of antidepressants in PPD treatment
Considering that the neuroprotective role of the Brain-derived neurotrophic factor (BDNF) pathway has been reported in previous studies and combining evidence from other depression studies, we hypothesized that the inhibition of autophagy in microglia may have a detrimental effect on fluoxetine treatment for PPD through upregulation of inflammation and reduced BDNF expression
Summary
Postpartum depression (PPD) is often accompanied by extreme sadness and hopelessness, low energy, anxiety, crying episodes, irritability, and infanticide [1, 2]. Inhibited Autophagy Affects Postpartum Depression [5], subsequently leading to devastating outcomes to family and society Numerous factors such as the interaction effect of genetic and epigenetic susceptibilities combined with environmental risk factors, such as stress, hormonal level change, and emotional trauma may account for the emergence of PPD. Since the role of autophagy in PPD pathogenesis is ambiguous, this study investigates whether the inhibition of autophagy in microglia arouses inflammation, further influencing the usage of antidepressants in PPD treatment. Considering that the neuroprotective role of the BDNF pathway has been reported in previous studies and combining evidence from other depression studies, we hypothesized that the inhibition of autophagy in microglia may have a detrimental effect on fluoxetine treatment for PPD through upregulation of inflammation and reduced BDNF expression
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