کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
937210 1645018 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice
چکیده انگلیسی

Misfolded amyloid beta peptide (Aβ) is a pathological hallmark of Alzheimer’s disease (AD), a neurodegenerative illness characterized by cognitive deficits and neuronal loss. Transgenic mouse models of Aβ over-production indicate that Aβ-induced cognitive deficits occur in the absence of overt neuronal death, suggesting that while extensive neuronal death may be associated with later stages of the human disease, subtle physiological changes may underlie initial cognitive deficits. Therefore, identifying signaling elements involved in those Aβ-induced cognitive impairments that occur prior to loss of neurons may reveal new potential pharmacological targets. Here, we report that the enzymatic activity of calcineurin, a key protein phosphatase involved in phosphorylation-dependent kinase activity crucial for synaptic plasticity and memory function, is upregulated in the CNS of the Tg2576 animal model for Aβ over-production. Furthermore, acute treatment of Tg2576 mice with the calcineurin inhibitor FK506 (10 mg/kg i.p.) improves memory function. These results indicate that calcineurin may mediate some of the cognitive effects of excess Aβ such that inhibition of calcineurin shall be further explored as a potential treatment to reverse cognitive impairments in AD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Learning and Memory - Volume 88, Issue 2, September 2007, Pages 217–224
نویسندگان
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