Abnormal calcium activity and CREB phosphorylation are associated with motor memory impairment in presenilin-1 mutant knock-in mice Journal Article
| Authors: | Lin, Y.; Bai, Y.; Martin-Avila, A.; Li, W.; Wu, X.; Ziff, E.; Gan, W. B. |
| Article Title: | Abnormal calcium activity and CREB phosphorylation are associated with motor memory impairment in presenilin-1 mutant knock-in mice |
| Abstract: | Introduction: Presenilin (PS) gene mutations cause memory impairment in early-onset familial Alzheimer's disease (FAD), but the underlying mechanisms remain unclear. Methods: We examined the effects of the PS1 M146V FAD mutation on motor learning, motor learning-related changes in neuronal Ca2+activity and CREB phosphorylation in the primary motor cortex. Results: We found that PS1 M146V knock-in mice displayed long-term deficiencies in motor skill learning. Ca2+ levels are altered in a cortical layer and neuron type-specific manner in PS1 mutant mice as compared to WT control mice. Notably, while running caused a significant increase of CREB phosphorylation in WT mice, it led to a significant decrease of CREB phosphorylation in layer 5 neurons of mutant mice. Discussion: These findings suggest that alterations of Ca2+ activity and CREB phosphorylation in deep cortical layers are early events leading to memory impairment in the PS1 mutation-related familial form of AD. © 2025 |
| Keywords: | immunohistochemistry; controlled study; protein phosphorylation; unclassified drug; gene mutation; nonhuman; protein function; mouse; mouse mutant; familial disease; confocal microscopy; image analysis; animal experiment; transcription factor; calcium; in vivo study; down regulation; upregulation; memory disorder; motor performance; amnesia; alzheimer disease; knockout mouse; presenilin 1; molecular pathology; alzheimer's disease; calcium ion; rotarod test; pyramidal nerve cell; memory deficits; primary motor cortex; time interval; male; female; article; transcription factor creb; adeno associated virus vector; motor learning; creb phosphorylation; in vivo ca<sup>2+</sup> imaging; brain cortex layer; long term memory deficit; short term memory deficit |
| Journal Title: | Cell Calcium |
| Volume: | 130 |
| ISSN: | 0143-4160 |
| Publisher: | Elsevier Ltd |
| Date Published: | 2025-09-01 |
| Start Page: | 103048 |
| Language: | English |
| DOI: | 10.1016/j.ceca.2025.103048 |
| PROVIDER: | scopus |
| PUBMED: | 40609403 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
