Research progress of non-monoamine antidepressants

Background Previous studies have shown that depression is often accompanied by an increase in mtDNA copy number and a decrease in ATP levels; however, the exact regulatory mechanisms remain unclear. Methods In the present study, Western blot, cell knockdown, immunofluorescence, immunoprecipitation and ChIP-qPCR assays were used to detect changes in the Ahi1/GR-TFAM-mtDNA pathway in the brains of neuronal Abelson helper integration site-1 (Ahi1) KO mice and dexamethasone (Dex)-induced mice to elucidate the pathogenesis of depression. In addition, a rescue experiment was performed to determine the effects of regular exercise on the Ahi1/GR-TFAM-mtDNA-ATP pathway and depression-like behavior in Dex-induced mice and Ahi1 KO mice under stress. Results In this study, we found that ATP levels decreased and mitochondrial DNA (mtDNA) copy numbers increased in depression-related brain regions in Dex-induced depressive mice and Ahi1 knockout (KO) mice. In addition, Ahi1 and glucocorticoid receptor (GR), two important proteins related to stress and depressive behaviors, were significantly decreased in the mitochondria under stress. Intriguingly, GR can bind to the D-loop control region of mitochondria and regulate mitochondrial replication and transcription. Importantly, regular exercise significantly increased mitochondrial Ahi1/GR levels and ATP levels and thus improved depression-like behaviors in Dex-induced depressive mice but not in Ahi1 KO mice under stress. Conclusions In summary, our findings demonstrated that the mitochondrial Ahi1/GR complex and TFAM coordinately regulate mtDNA copy numbers and brain ATP levels by binding to the D-loop region of mtDNA Regular exercise increases the levels of the mitochondrial Ahi1/GR complex and improves depressive behaviors.

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The mitochondrial Ahi1/GR participates the regulation on mtDNA copy numbers and brain ATP levels and modulates depressive behaviors in mice

Wang

Shi

et al. 2023

Cell Commun Signal

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The neural mechanism of the different sub-regions of hippocampus involved in post-traumatic stress disorder

Zuo¹,

Zhou²,

Zhou³

et al. 2022

Stress and Brain

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post-traumatic stress disorder (PTSD), under water trauma (UWT) model rats, long-term depression, alpha calcium/calmodulin-dependent protein kinase II (αCaMKII) Post-traumatic stress disorder (PTSD) patients have severe fear extinction disorder, but the underlying molecular and neurobiological mechanisms are still unknown. The hippocampus has sub-regional specific functions, however, their involvement in PTSD is unclear. In this study, we used under water trauma (UWT) model rats which exhibit multiple core PTSD symptoms, including anxiety, depression, and impaired fear extinction. In the dorsal or ventral hippocampus, we found that long-term depression at Schaffer collateral and medial perforant pathway were impaired in UWT model rats. Moreover, although the expression levels of ionotropic glutamate receptors including NR2A, NR2B, GluA1, and GluA2 were normal, the activity of alpha calcium/calmodulin-dependent protein kinase II (αCaMKII) significantly increased in both the dorsal and ventral hippocampus of UWT model rats. These findings reveal similar abnormalities in synaptic plasticity and αCaMKII activity in different hippocampal sub-regions of UWT rats. Our results shed light on the regionspecific role of the hippocampus in PTSD and provide a theoretical basis for the development of specific treatments for PTSD.

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Research progress of non-monoamine antidepressants

Cited by 2 publications

References 104 publications

The mitochondrial Ahi1/GR participates the regulation on mtDNA copy numbers and brain ATP levels and modulates depressive behaviors in mice

The mitochondrial Ahi1/GR participates the regulation on mtDNA copy numbers and brain ATP levels and modulates depressive behaviors in mice

The neural mechanism of the different sub-regions of hippocampus involved in post-traumatic stress disorder

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