ArticleMolecular psychiatry2018
Protein kinase Mζ in medial prefrontal cortex mediates depressive-like behavior and antidepressant response.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Structural Neurotoxic and Neuroprotective Effects of Ketamine and Esketamine in Preclinical and Human Studies: A Systematic Review.Research square · 2026Article
- Efficacy of Venlafaxine and Deep Brain Stimulation Against the Effects of Hippocampal Lesion with Ibotenic Acid in Animals Exposed to the Chronic Mild Stress Model of Depression.Current neuropharmacology · 2026Article
- Review
- Altered synaptic homeostasis: a key factor in the pathophysiology of depression.Cell & bioscience · 2025Review
- Neurotoxic lesions of the anterior claustrum influence cued fear memory in rats.Frontiers in psychiatry · 2024Article
- Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.Neurochemical research · 2023Article
- Sex differences in pre- and post-synaptic glutamate signaling in the nucleus accumbens core.Biology of sex differences · 2023Article
- AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models.Translational psychiatry · 2023Article
- Environment Enrichment Facilitates Long-Term Memory Consolidation through Behavioral Tagging.eNeuro · 2023Article
- DNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKMζ.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- Taurine Alleviates Chronic Social Defeat Stress-Induced Depression by Protecting Cortical Neurons from Dendritic Spine Loss.Cellular and molecular neurobiology · 2023Article
- Research hotspots and trends on neuropathic pain-related mood disorders: a bibliometric analysis from 2003 to 2023.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- TAAR1 regulates drug-induced reinstatement of cocaine-seeking via negatively modulating CaMKIIα activity in the NAc.Molecular psychiatry · 2022Article
- Involvement of PKMζ in Stress Response and Depression.Frontiers in cellular neuroscience · 2022Review
- Beneficial effects of running exercise on hippocampal microglia and neuroinflammation in chronic unpredictable stress-induced depression model rats.Translational psychiatry · 2021Article
- Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression.Molecular brain · 2020Article
- Entorhinal cortex-based metabolic profiling of chronic restraint stress mice model of depression.Aging · 2020Article
- Differentially Expressed Genes in the Brain of Aging Mice With Cognitive Alteration and Depression- and Anxiety-Like Behaviors.Frontiers in cell and developmental biology · 2020Article
- The Claustrum-Prefrontal Cortex Pathway Regulates Impulsive-Like Behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Differential Release of Exocytosis Marker Dyes Indicates Stimulation-Dependent Regulation of Synaptic Activity.Frontiers in neuroscience · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal atrophy and alterations of synaptic structure and function in the medial prefrontal cortex (mPFC) have been implicated in the pathogenesis of depression, but the underlying molecular mechanisms are largely unknown. The protein kinase Mζ (PKMζ), a brain-specific atypical protein kinase C isoform, is important for maintaining long-term potentiation and storing memory. In the present study, we explored the role of PKMζ in mPFC in two rat models of depression, chronic unpredictable stress (CUS) and learned helplessness. The involvement of PKMζ in the antidepressant effects of conventional antidepressants and ketamine were also investigated. We found that chronic stress decreased the expression of PKMζ in the mPFC and hippocampus but not in the orbitofrontal cortex. Overexpression of PKMζ in mPFC prevented the depressive-like and anxiety-like behaviors induced by CUS, and reversed helplessness behaviors. Inhibition of PKMζ in mPFC by expressing a PKMζ dominant-negative mutant induced depressive-like behaviors after subthreshold unpredictable stress and increased learned helplessness behavior. Furthermore, stress-induced deficits in synaptic proteins and decreases in dendritic density and the frequency of miniature excitatory postsynaptic currents in the mPFC were prevented by PKMζ overexpression and potentiated by PKMζ inhibition in subthreshold stress rats. The antidepressants fluoxetine, desipramine and ketamine increased PKMζ expression in mPFC and PKMζ mediated the antidepressant effects of ketamine. These findings identify PKMζ in mPFC as a critical mediator of depressive-like behavior and antidepressant response, providing a potential therapeutic target in developing novel antidepressants.
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