ArticleFrontiers in behavioral neuroscience2021
HINT1 Is Involved in the Chronic Mild Stress Elicited Oxidative Stress and Apoptosis Through the PKC ε/ALDH-2/4HNE Pathway in Prefrontal Cortex of Rats.
Article in Frontiers in behavioral neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Mitochondrial-inflammation crosstalk in major depressive disorder: molecular mechanisms and therapeutic implications.Molecular psychiatry · 2026Pooled it
- Treadmill Exercise in Rats Attenuates Chronic Unpredictable Stress-Induced Depressive-like Behavior Associated with Melatonin-SIRT1/Nrf2 Signaling in the Prefrontal Cortex.Physiological research · 2026Article
- Deletion of Murine Endothelial <italic>Bag3</italic> Alters the Cellular Proteome among Organs of Origin.Journal of vascular research · 2026Article
- ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.Military Medical Research · 2025Review
- Targeting HINT1 to improve synaptic plasticity: toward loganin as a new antidepressant strategy.Molecular psychiatry · 2025Article
- Converged avenues: depression and Alzheimer's disease- shared pathophysiology and novel therapeutics.Molecular biology reports · 2024Review
- Histidine Triad Nucleotide-Binding Protein 1 Improves Critical Limb Ischemia by Regulating Mitochondrial Homeostasis.Nutrients · 2023Article
- Identification of Genetic Variations in the NAD-Related Pathways for Patients with Major Depressive Disorder: A Case-Control Study in Taiwan.Journal of clinical medicine · 2022Article
- Electrolytic lesions of the bilateral ventrolateral orbital cortex not only directly reduce depression-like behavior but also decreased desperate behavior induced by chronic unpredicted mild stress in rats.BMC neuroscience · 2021Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major depressive disorder (MDD) is a severe, highly heterogeneous, and life-threatening psychiatric disease which affects up to 21% of the population worldwide. A new hypothesis suggests that the mitochondrial dysfunction causing oxidative stress (OS) and dysregulation of apoptosis in brain might be one of the key pathophysiological factors in MDD. Histidine triad nucleotide binding protein 1 (HINT1), which was first supposed to be protein kinase C (PKC) inhibitor, has been gradually demonstrated to be involved in diverse neuropsychiatric diseases. It still remains elusive that how HINT1 involves in depression. The present study utilized a rat model exposed to chronic mild stress (CMS) to explore the involvement of HINT1 in depression. Face validity, construct validity and predictive validity of CMS model were comprehensive evaluated in this study. Behavioral tests including sucrose preference test, open field test, and elevated plus maze and forced swimming test revealed that stressed rats displayed elevated level of anxiety and depression compared with the controls. CMS rats showed a significant decrease of superoxide dismutase, and a marked increase malondialdehyde levels in prefrontal cortex (PFC). We also found the CMS rats had elevated expression of HINT1, decreased levels of phosphorylated-PKC ε and aldehyde dehydrogenase-two (ALDH-2), and accumulated 4-hydroxynonenal (4HNE) in PFC. Moreover, CMS increased the levels of cleaved caspase-3 and Bax, and decreased the level of Bcl-2 in PFC. The alterations in behavior and molecule were prevented by antidepressant venlafaxine. These results demonstrated that HINT1 was involved in the CMS elicited OS and apoptosis in PFC, probably through the PKC ε/ALDH-2/4HNE pathway. The results suggest that the suppression of HINT1 might have potential as a novel therapeutic strategy for depression.
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