Long-term memory formation requires gene expression and new protein synthesis. MicroRNAs (miRNAs), a family of small non-coding RNAs that inhibit target gene mRNA expression, are involved in new memory formation. In this study, elevated miR-151-5p (miR-151) levels were found to be responsible for hippocampal contextual fear memory formation. Using a luciferase reporter assay, we demonstrated that miR-151 targets APH1a, a protein that has been identified as a key factor in γ-secretase activity, namely APH1a. Blocking miR-151 can upregulate APH1a protein levels and subsequently impair hippocampal fear memory formation. These results indicate that miR-151 is involved in hippocampal contextual fear memory by inhibiting APH1a protein expression. This work provides novel evidence for the role of miRNAs in memory formation and demonstrates the implication of APH1a protein in miRNA processing in the adult brain.
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http://dx.doi.org/10.1080/15476286.2019.1572435 | DOI Listing |
Acta Neuropathol Commun
January 2025
Department of Biological Sciences, Purdue University, 915 Mitch Daniels Blvd, West Lafayette, IN, USA.
Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.
View Article and Find Full Text PDFNeuroscience
January 2025
Department of Molecular Anatomy, School of Medicine University of the Ryukyus, Uehara, 207, Nishihara, Okinawa 903-0213, Japan.
The subiculum is a main output part of the hippocampal formation and important for learning and memory. According to connection studies, the distal and proximal regions of the subiculum project to the brain regions related to the spatial and emotional memories, respectively. Our previous morphological studies indicated that the ventral subiculum (vSub) consists of two regions, the distal subiculum (Sub1) and the proximal subiculum (Sub2), while the dorsal subiculum (dSub) seemed to comprise only one region (Sub1).
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Weijin Road, 300072 Tianjin, China. Electronic address:
Ethnopharmacological Relevance: Originally formulated to mitigate high-altitude sickness, Xinnaoxin capsules (XNX) are composed of three traditional Chinese medicines (Rhodiola rosea L., Lycium barbarum L. and Hippophae rhamnoides) with properties of anti-hypoxia, anti-fatigue, and anti-aging.
View Article and Find Full Text PDFJ Transl Med
January 2025
Research Unit NeuroBiology of Diabetes, Helmholtz Munich, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
Background: Obese subjects undergoing weight loss often fear the Yoyo dieting effect, which involves regaining or even surpassing their initial weight. To date, our understanding of such long-term obesity and weight cycling effects is still limited and often based on only short-term murine weight gain and loss studies. This study aimed to investigate the long-term impacts of weight cycling on glycemic control and metabolic health, focusing on adipose tissue, liver, and hypothalamus.
View Article and Find Full Text PDFAlzheimers Res Ther
January 2025
Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.
Background: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.
Methods: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1, PSEN2, and APP and mechanistically characterized by integrating RNA-seq and ATAC-seq.
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