We show for the first time that hippocampal GABAergic function is impaired by pathological tau protein, leading to altered synaptic plasticity and severe memory deficits.
Our data demonstrated that human Val97Leu mutant presenilin-1 causes spatial memory deficit in mice and increases tau phosphorylation level in glycogen synthase kinase-3-dependent manner.
To investigate whether GSK-3 inhibition can reduce amyloid and tau pathologies, neuronal cell death and memory deficits in vivo, double transgenic mice coexpressing human mutant APP and tau were treated with a novel non-ATP competitive GSK-3beta inhibitor, NP12.
Mutant Tg2576 mice which possess the human "Swedish" APP mutation have been shown to demonstrate both Abeta plaque pathology and memory deficits in behavioral tasks.
A recently described mouse line, Tg(HuAPP695.K670N/M671L)2576, expressing human amyloid precursor protein with a familial AD gene mutation, age-related amyloid deposits, and memory deficits, was found to develop a significant microglial response using Griffonia simplicifolia lectin or phosphotyrosine probe to identify microglia Both Griffonia simplicifolia lectin and phosphotyrosine staining showed increased numbers of intensely labeled, often enlarged microglia clustered in and around plaques, consistent with microglial activation related to beta-amyloid formation.
Transgenic mice that overexpress the Swedish mutation of human amyloid precursor protein (hAPPswe; Tg2576) show age-dependent memory deficits in hippocampus-dependent learning tasks.
This approach allowed us to isolate a fraction (MpF10) with anti-inflammatory activity, able to ameliorate the spatial learning and memory impairment, and to reduce both astrogliosis as well as IL-1β and TNF production in a murine model of LPS-mediated neuroinflammation.
Results demonstrated that: (a) a moderate treadmill running exercise prevented spatial learning and memory deficits in aged rats; (b) training in the Water maze increased both Na<sup>+</sup>, K<sup>+</sup>-ATPase and AChE activities in the hippocampus of mature and aged rats; (c) aged exercised rats displayed an even further increase of Na<sup>+</sup>, K<sup>+</sup>-ATPase activity in the hippocampus, (d) enzyme activity correlated with memory performance in aged rats.
Specifically, carriage of the ADRA2B deletion abolished the relative memory impairment in homozygous COMT val(158) carriers compared to met(158) carriers.
In vivo electrophysiology in behaving mice showed that long-term potentiation in the hippocampus of 5-HT-deficient mice was altered, and administration of the 5-HT1A agonist 8-OHDPAT rescued the memory deficits.
The short (s) allele of 5-HTTLPR has been linked to greater susceptibility for impaired memory and smaller hippocampal volume compared to the long allele (l).
The memory deficits we observed in mouse prion disease were completely restored by treatment with benzyl quinolone carboxylic acid (BQCA) and benzoquinazoline-12 (BQZ-12), two highly selective positive allosteric modulators (PAMs) of M1 mAChRs.
After the onset of memory deficits in 3xTg-AD mice, a three weeks treatment with the selective A<sub>2A</sub>R antagonist normalized the up-regulation of hippocampal A<sub>2A</sub>R and restored hippocampal-dependent reference memory, as well as the decrease of hippocampal synaptic plasticity (60.0 ± 3.7% decrease of long-term potentiation amplitude) and the decrease of global (syntaxin-I) and glutamatergic synaptic markers (vGluT1).
Mapping self-reports of working memory deficits to executive dysfunction in Fragile X Mental Retardation 1 (FMR1) gene premutation carriers asymptomatic for FXTAS.
Neuropsychological evaluation reveals a significant recognition memory deficit in patients with a GRN mutation but a significant language deficit only in patients without a GRN mutation.
Exposure to PQ significantly increased total WBC, neutrophil, eosinophil, lymphocyte, and monocyte counts, IL-10, interferon gama (INF-γ), nitrite (NO<sub>2</sub>), and malondialdehyde (MDA) levels, but catalase (CAT), superoxide dismutase (SOD), and thiol levels were decreased (<i>p</i> < 0.05 to <i>p</i> < 0.00).<i>Z. multiflora</i> and dexamethasone treatment significantly improved all behavioral as well as lung changes induced by inhaled PQ (<i>p</i> < 0.05 to <i>p</i> < 0.01).<b>Conclusion:</b><i>Z. multiflora</i> treatment improved learning and memory impairment as well as lung inflammation and oxidative stress induced by inhaled PQ.
Moreover, constitutive deletion of the Aβo-binding cellular prion protein (PrP<sup>C</sup>) prevents development of memory deficits in APP<sub>swe</sub>/PS1ΔE9 mice, a model of familial AD.
In TUBA4A, we detected a novel frameshift mutation (p.Arg64Glyfs*90) leading to a truncated protein in 1 FTD patient (1/459 of 0.22%) with family history of Parkinson's disease and cognitive impairment, and a novel missense mutation (p.Thr381Met) in 2 sibs with familial ALS and memory problems (1 index patient/429, 0.23%) in whom we previously identified a pathogenic Chromosome 9 open reading frame 72 repeat expansion mutation.