scholarly journals Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.

1996 ◽  
Vol 184 (4) ◽  
pp. 1425-1433 ◽  
Author(s):  
Y Vodovotz ◽  
M S Lucia ◽  
K C Flanders ◽  
L Chesler ◽  
Q W Xie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nitric Oxide Synthase ◽  
No Production ◽  
Tgf Beta ◽  
Control Subjects ◽  
Human Neurons ◽  
Oxide Synthase ◽  
High Output

In Alzheimer's disease (AD), affected neurons accumulate beta amyloid protein, components of which can induce mouse microglia to express the high-output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice, NOS2 is normally suppressed by transforming growth factor beta 1 (TGF-beta 1). Expression of TGF-beta 1 is decreased in brains from AD patients, a situation that might be permissive for accumulation of NOS2. Accordingly, we investigated the expression of NOS2 in patients with AD, using three monospecific antibodies: a previously described polyclonal and two new monoclonal antibodies. Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was undetectable in brains from 6 control subjects aged 23-72 years, but was expressed in small amounts in 3 control subjects aged 77-87 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD.

Metallothionein-3 and neuronal nitric oxide synthase levels in brains from the Tg2576 mouse model of Alzheimer's disease

2006 ◽  
Vol 283 (1-2) ◽  
pp. 129-137 ◽  
Author(s):  
Bruce L. Martin ◽  
Abigail M. Tokheim ◽  
Patrick T. McCarthy ◽  
Brendan S. Doms ◽  
Andrew A. Davis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nitric Oxide Synthase ◽  
Mouse Model ◽  
Neuronal Nitric Oxide Synthase ◽  
Tg2576 Mouse ◽  
Model Of Alzheimer’S Disease ◽  
Oxide Synthase

Does Nitric Oxide Synthase Contribute to the Pathogenesis of Alzheimer's Disease?

2003 ◽  
Vol 1010 (1) ◽  
pp. 639-642 ◽  
Author(s):  
D K. LAHIRI ◽  
D CHEN ◽  
Y-W GE ◽  
M FARLOW ◽  
G KOTWAL ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nitric Oxide Synthase ◽  
Oxide Synthase

scholarly journals NITRIC OXIDE SYNTHASE DYSFUNCTION UNDERLIES CEREBROVASCULAR DEFICITS IN A MOUSE MODEL OF TAUOPATHY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S91-S91
Author(s):  
Candice E Van Skike ◽  
Stacy A Hussong ◽  
Andy Banh ◽  
Veronica Galvan
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Mouse Model ◽  
Doppler Flowmetry ◽  
Cerebrovascular Dysfunction ◽  
Oxide Synthase

Abstract We recently identified pathogenic soluble aggregated tau (tau oligomers) in the cerebral microvasculature of human patients with tauopathies, including Alzheimer’s disease (AD). The functional consequences of cerebrovascular tau accumulation are not yet understood. The aim of the present study was to determine whether pathogenic tau accumulation leads to cerebrovascular dysfunction. To this end, we measured neurovascular coupling (NVC), a highly regulated process that synchronizes cerebral blood flow to neuronal activation, using the PS19(P301S) mouse model of tauopathy. The change in cerebral blood flow evoked by whisker stimulation was measured using Laser Doppler flowmetry in PS19 and wildtype control mice and the functional contribution of neuronal and endothelial nitric oxide synthase (nNOS and eNOS, respectively) was calculated. Vascular reactivity was assessed using topical acetylcholine to evoke endothelium-dependent vasodilation. To assess the direct impact of pathogenic tau on cell-specific NOS function, we treated N2a neuroblastoma cells or mouse brain vascular endothelial cells with soluble tau aggregates and measured activity of nNOS and eNOS. Our data indicate isolated overexpression of mutant tau impairs NVC responses, and this deficit is mediated by a reduction in nNOS activity in vivo. Further, our studies suggest tauopathy also impairs endothelium-dependent vasoreactivity in the cortex. Additionally, soluble tau aggregates inhibit the phosphorylation of NOS in primary cultured cells. Therefore, inhibition of NOS phosphorylation by pathogenic soluble tau aggregates may underlie cerebrovascular dysfunction in tauopathies. Thus, therapeutic modulation of pathogenic tau may mitigate brain microvascular deficits, which occur prior to clinical onset in Alzheimer’s disease and potentially other tauopathies.

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