کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4932841 | 1433534 | 2017 | 23 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Forebrain depletion of Rheb GTPase elicits spatial memory deficits in mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
The precise molecular and cellular events responsible for age-dependent cognitive dysfunctions remain unclear. We report that Rheb (ras homolog enriched in brain) GTPase, an activator of mammalian target of rapamycin (mTOR), regulates memory functions in mice. Conditional depletion of Rheb selectively in the forebrain of mice obtained from crossing Rhebf/f and CamKIICre results in spontaneous signs of age-related memory loss, that is, spatial memory deficits (T-maze, Morris water maze) without affecting locomotor (open-field test), anxiety-like (elevated plus maze), or contextual fear conditioning functions. Partial depletion of Rheb in forebrain was sufficient to elicit memory defects with little effect on the neuronal size, cortical thickness, or mammalian target of rapamycin activity. Rheb depletion, however, increased the levels of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), a protein elevated in aging and Alzheimer's disease. Overall, our study demonstrates that forebrain Rheb promotes aging-associated cognitive defects. Thus, molecular understanding of Rheb pathway in brain may provide new therapeutic targets for aging and/or Alzheimer's disease-associated memory deficits.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 50, February 2017, Pages 134-143
Journal: Neurobiology of Aging - Volume 50, February 2017, Pages 134-143
نویسندگان
Neelam Shahani, Wen-Chin Huang, Megan Varnum, Damon T. Page, Srinivasa Subramaniam,