دانلود مقاله ISI انگلیسی شماره 30803
عنوان فارسی مقاله

بررسی اثر اختلال حرکتی ، یک داروی ضد صرع، اختلالات حافظه بر روی ارتباط با پیری و بیماری آلزایمر در موش

کد مقاله سال انتشار مقاله انگلیسی ترجمه فارسی تعداد کلمات
30803 2013 5 صفحه PDF سفارش دهید محاسبه نشده
خرید مقاله
پس از پرداخت، فوراً می توانید مقاله را دانلود فرمایید.
عنوان انگلیسی
Effects of levetiracetam, an antiepileptic drug, on memory impairments associated with aging and Alzheimer’s disease in mice
منبع

Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)

Journal : Neurobiology of Learning and Memory, Volume 102, May 2013, Pages 7–11

کلمات کلیدی
داروی ضد صرع - پیری - بیماری آلزایمر - یادگیری و حافظه - تهویه ترس ’
پیش نمایش مقاله
پیش نمایش مقاله بررسی اثر اختلال حرکتی ، یک داروی ضد صرع، اختلالات حافظه بر روی ارتباط با پیری و بیماری آلزایمر در موش

چکیده انگلیسی

Emerging evidence suggests that elevated hippocampal activation may be important for disrupting cognitive functions in aged subjects as well as patients with Alzheimer’s disease (AD). Therefore, reducing deleterious overactivity of the hippocampus may have therapeutic benefits. This study was designed to compare the effects of levetiracetam, an antiepileptic drug, on memory deficits associated with normal aging and AD in mouse models. Pretraining administration of levetiracetam ameliorated memory impairments of aged C57BL/6 mice (17–20 months of age) in the contextual fear conditioning paradigm. Acute levetiracetam immediately after training was also efficacious in rescuing contextual memory decline in aged mice, whereas administration at a later posttraining interval (3 h) had no effect. These results suggest that suppressing overexcitation with acute levetiracetam around the time of acquisition or early consolidation may be sufficient to reverse memory decline associated with aging. In contrast, pretraining administration of levetiracetam was not able to rescue memory deficits in 5XFAD transgenic mice harboring amyloid plaque pathologies at moderate (6–8 months old) or massive (12–15 months old) levels, differentiating between normal aging- and AD-related memory impairments in the responsiveness to acute levetiracetam treatment.

مقدمه انگلیسی

Normal aging is often accompanied by a decline in memory functions that depend on the hippocampus, in the absence of age-associated diseases such as Alzheimer’s disease (AD). Although the underlying neurobiological mechanisms have not been fully understood, recent evidence suggests that excess neural activity in the CA3 region of the hippocampus occurs in aged rodents with memory impairment when these neurons are unable to encode new information (Wilson et al., 2006 and Wilson et al., 2005). Consistent with these findings, studies with functional magnetic resonance imaging (fMRI) have successfully detected increased hippocampal activation such as a specific pattern of hyperactivity in the CA3/dentate gyrus (DG) region in elderly humans with mild cognitive impairment (MCI), a transient phase between normal aging and AD (Ewers et al., 2011 and Yassa et al., 2010). Moreover, it is demonstrated that treatments targeting elevated neuron activity, including administration of low-dose antiepileptic agents, can improve cognition in aged rats (Koh et al., 2010 and Koh et al., 2013) and patients with MCI (Bakker et al., 2012), supporting the idea that the overactive hippocampal system may represent a dysfunctional condition leading to memory impairments associated with aging or MCI. Intriguingly, the neuronal overexcitation is also hypothesized to play a role in progression on the path to AD conditions (Gallagher & Koh, 2011). For example, hippocampal hyperactivation during memory testing in individuals with MCI has been reported to predict greater subsequent cognitive decline and conversion to AD-related neurodegeneration (Miller et al., 2008 and Putcha et al., 2011). Recent investigations of transgenic mice overexpressing amyloid precursor protein (APP) have revealed amyloid-β (Aβ)-associated hyperactive neurons and aberrant excitatory network activity or nonconvulsive seizures in the hippocampus and cerebral cortex (Busche et al., 2008, Minkeviciene et al., 2009, Palop and Mucke, 2010, Palop et al., 2007 and Ziyatdinova et al., 2011), although a causal link between the hyperexcitability and memory deficits in these AD models remains unclear. In this study, we examined the effects of pretraining or posttraining administration of levetiracetam, an antiepileptic drug, on memory impairments associated with normal aging in C57BL/6 mice. Furthermore, the effects were compared with those on memory deficits in 5XFAD transgenic mice, which provide a rapid-onset and aggressive amyloid model based on a combination of five familial AD (FAD) mutations and the consequent acceleration of Aβ42 production (Oakley et al., 2006, Ohno et al., 2006 and Ohno et al., 2007). We found that an acute injection of levetiracetam around the time of acquisition or early consolidation is efficacious in rescuing memory decline in aged C57BL/6 mice in the contextual fear conditioning task, while it has no effects on memory deficits in 5XFAD mice at pathological stages developing moderate (6–8 months of age) to massive (12–15 months of age) levels of Aβ plaque deposition.

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