Ezh2 is a catalytic subunit of the polycomb repressive complex 2 (PRC2) which mediates epigenetic gene silencing through depositing the mark histone H3 lysine 27 trimethylation (H3K27me3) at target genomic sequences. Previous studies have demonstrated that Enhancer of Zeste Homolog 2 (Ezh2) was differentially expressed during maturation of hippocampal neurons; in immature neurons, Ezh2 was abundantly expressed, whereas in mature neurons the expression Ezh2 was significantly reduced. Here, we report that Ezh2 is downregulated by microRNAs (miRs) that are expressed during the hippocampal maturation process. We show that, in mature hippocampal neurons, lethal-7 (let-7) and microRNA-124 (miR-124) are robustly expressed and can target cognate motifs at the 3'-UTR of the Ezh2 gene sequence to downregulate Ezh2 expression. Together, these data demonstrate that the PRC2 repressive activity during hippocampal maturation is controlled through a post-transcriptional mechanism that mediates Ezh2 downregulation in mature neurons.
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http://dx.doi.org/10.3390/ijms21228472 | DOI Listing |
Mol Psychiatry
January 2025
Institut de Neurociències, Department de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Alzheimer's disease (AD) is characterized by memory loss and neuropsychiatric symptoms associated with cerebral amyloid-β (Aβ) and tau pathologies, but whether and how these factors differentially disrupt neural circuits remains unclear. Here, we investigated the vulnerability of memory and emotional circuits to Aβ and tau pathologies in mice expressing mutant human amyloid precursor protein (APP), Tau or both APP/Tau in excitatory neurons. APP/Tau mice develop age- and sex-dependent Aβ and phosphorylated tau pathologies, the latter exacerbated at early stages, in vulnerable brain regions.
View Article and Find Full Text PDFJ Nutr
January 2025
Jean Mayer USDA HNRCA, Tufts University, Boston, MA 02111.
Background: In addition to its important roles in blood coagulation and bone formation, vitamin K (VK) contributes to brain function. Low dietary VK intake, which is common among older adults, is associated with age-related cognitive impairment.
Objective: To elucidate the biological mechanisms underlying VK's effects on cognition, we investigated the effects of low VK (LVK) intake on cognition in C57BL/6 mice.
J Ethnopharmacol
January 2025
Health Medical Center, Hubei Minzu University, Enshi, Hubei, 445000, PR China; Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Disease, Hubei Minzu University, Enshi, Hubei, 445000, PR China. Electronic address:
Ethnopharmacological Relevance: Qiangji Decoction (QJD), a Chinese medicine, is widely used in Traditional Chinese Medicine to treat amnesia and Alzheimer's disease (AD), showing significant anti-AD effects. However, the precise mechanisms behind these effects are not well understood and require more research.
Aim Of The Study: This study aims to elucidate the mechanisms by which QJD ameliorates neuronal damage, synaptic dysfunction, and mitochondrial impairment in AD through the regulation of ROCK2/Drp1-mediated mitochondrial dynamics.
Proc Natl Acad Sci U S A
February 2025
Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD 21218.
The hippocampal dentate gyrus (DG) is thought to orthogonalize inputs from the entorhinal cortex (pattern separation) and relay this information to the CA3 region. In turn, attractor dynamics in CA3 perform a pattern completion or error correction operation before sending its output to CA1. In a mouse model of congenital hypoplasia of the DG, a deficiency in the (Wls) gene, specifically in cells expressing , which targets neuronal progenitors, led to an almost total absence of dentate granule cells and modestly impaired performance in spatial tasks.
View Article and Find Full Text PDFScience
January 2025
Department of Neuroscience, University of California, Berkeley, Berkeley, CA, USA.
The mechanisms by which the brain replays neural activity sequences remain unknown. Recording from large ensembles of hippocampal place cells in freely behaving rats, we observed that replay content is strictly organized over multiple timescales and governed by self-avoidance. After movement cessation, replays avoided the animal's previous path for 3 seconds.
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