Matching Items (385)
ContributorsWard, Geoffrey Harris (Performer) / ASU Library. Music Library (Publisher)
Created2018-03-18
Description
Patients with Alzheimer's disease (AD) exhibit a significantly higher incidence of unprovoked seizures compared to age-matched non-AD controls, and animal models of AD (i.e., transgenic human amyloid precursor protein, hAPP mice) display neural hyper-excitation and epileptic seizures. Hyperexcitation is particularly important because it contributes to the high incidence of epilepsy in AD patients as well as AD-related synaptic deficits and neurodegeneration. Given that there is significant amyloid-β (Aβ) accumulation and deposition in AD brain, Aβ exposure ultimately may be responsible for neural hyper-excitation in both AD patients and animal models. Emerging evidence indicates that α7 nicotinic acetylcholine receptors (α7-nAChR) are involved in AD pathology, because synaptic impairment and learning and memory deficits in a hAPPα7-/- mouse model are decreased by nAChR α7 subunit gene deletion. Given that Aβ potently modulates α7-nAChR function, that α7-nAChR expression is significantly enhanced in both AD patients and animal models, and that α7-nAChR play an important role in regulating neuronal excitability, it is reasonable that α7-nAChRs may contribute to Aβ-induced neural hyperexcitation. We hypothesize that increased α7-nAChR expression and function as a consequence of Aβ exposure is important in Aβ-induced neural hyperexcitation. In this project, we found that exposure of Aβ aggregates at a nanomolar range induces neuronal hyperexcitation and toxicity via an upregulation of α7-nAChR in cultured hippocampus pyramidal neurons. Aβ up-regulates α7-nAChRs function and expression through a post translational mechanism. α7-nAChR up-regulation occurs prior to Aβ-induced neuronal hyperexcitation and toxicity. Moreover, inhibition of α7-nAChR or deletion of α7-nAChR prevented Aβ induced neuronal hyperexcitation and toxicity, which suggests that α7-nAChRs are required for Aβ induced neuronal hyperexcitation and toxicity. These results reveal a profound role for α7-nAChR in mediating Aβ-induced neuronal hyperexcitation and toxicity and predict that Aβ-induced up-regulation of α7-nAChR could be an early and critical event in AD etiopathogenesis. Drugs targeting α7-nAChR or seizure activity could be viable therapies for AD treatment.
ContributorsLiu, Qiang (Author) / Wu, Jie (Thesis advisor) / Lukas, Ronald J (Committee member) / Chang, Yongchang (Committee member) / Sierks, Michael (Committee member) / Smith, Brian (Committee member) / Vu, Eric (Committee member) / Arizona State University (Publisher)
Created2011
ContributorsBolari, John (Performer) / ASU Library. Music Library (Publisher)
Created2018-10-04
ContributorsOftedahl, Paul (Performer) / ASU Library. Music Library (Publisher)
Created2018-09-29
ContributorsMarshall, Kimberly (Performer) / Meszler, Alexander (Performer) / Yatso, Toby (Narrator) / ASU Library. Music Library (Publisher)
Created2018-09-16
ContributorsTaylor, Karen Stephens (Performer) / ASU Library. Music Library (Publisher)
Created2018-04-21
ContributorsCramer, Craig (Performer) / ASU Library. Music Library (Publisher)
Created1997-02-16
ContributorsMarshall, Kimberly (Performer) / ASU Library. Music Library (Publisher)
Created2019-03-17
ContributorsCampbell, Jeffrey (Performer) / ASU Library. Music Library (Publisher)
Created2005-10-23
ContributorsMarshall, Kimberly (Performer) / ASU Library. Music Library (Publisher)
Created2007-03-11