کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6808312 | 1433591 | 2012 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Medial septal dysfunction by Aβ-induced KCNQ channel-block in glutamatergic neurons
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Medial septal dysfunction by Aβ-induced KCNQ channel-block in glutamatergic neurons Medial septal dysfunction by Aβ-induced KCNQ channel-block in glutamatergic neurons](/preview/png/6808312.png)
چکیده انگلیسی
Amyloid β (Aβ) peptides play a central role in the pathophysiology of Alzheimer's disease (AD). The cellular mechanisms underlying Aβ toxicity, however, are poorly understood. Here we show that Aβ25-35 and Aβ1-40 acutely and differentially affect the characteristics of 3 classes of medial septum (MS) neurons in mice. In glutamatergic neurons Aβ increases firing frequency and blocks the A- and the M-current (IA and IM, respectively). While the IA block is similar in other MS neuron classes, the block of IM is specific to glutamatergic neurons. IM block and a simulated Aβ block mimic the Aβ-induced increase in spontaneous firing in glutamatergic neurons. Calcium imaging shows that under control conditions glutamatergic neurons rarely fire while nonglutamatergic neurons fire coherently at theta frequencies. Aβ increases the firing rate of glutamatergic neurons while nonglutamatergic neurons lose theta firing coherence. Our results demonstrate that Aβ-induced dysfunction of glutamatergic neurons via IM decrease diminishes MS rhythmicity, which may negatively affect hippocampal rhythmogenesis and underlie the memory loss observed in Alzheimer's disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 33, Issue 9, September 2012, Pages 2046-2061
Journal: Neurobiology of Aging - Volume 33, Issue 9, September 2012, Pages 2046-2061
نویسندگان
Richardson N. Leão, Luis V. Colom, Lotta Borgius, Ole Kiehn, André Fisahn,