Impaired theta-gamma coupling in APP-deficient mice

Scientific Reports, Год журнала: 2016, Номер 6(1)

Опубликована: Фев. 24, 2016

Abstract Amyloid precursor protein (APP) is critically involved in the pathophysiology of Alzheimer’s disease, but its physiological functions remain elusive. Importantly, APP knockout (APP-KO) mice exhibit cognitive deficits, suggesting that plays a role at neuronal network level. To investigate this possibility, we recorded local field potentials (LFPs) from posterior parietal cortex, dorsal hippocampus and lateral prefrontal cortex freely moving APP-KO mice. Spectral analyses showed oscillations within theta- gamma-frequency bands were not different between wild-type Surprisingly, however, while gamma amplitude coupled to theta phase all regions animals, theta-gamma coupling was strongly diminished recordings hippocampus, LFPs cortex. Thus, lack reduces oscillatory LFP specific brain regions, despite affecting oscillations. Together, our findings reveal reduced cross-frequency as functional marker deficiency

Язык: Английский

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APP Receptor? To Be or Not To Be

Trends in Pharmacological Sciences, Год журнала: 2016, Номер 37(5), С. 390 - 411

Опубликована: Янв. 31, 2016

Язык: Английский

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CRISPR/Cas9 editing of APP C-terminus attenuates β-cleavage and promotes α-cleavage

Nature Communications, Год журнала: 2018, Номер 10(1)

Опубликована: Дек. 28, 2018

CRISPR/Cas9 guided gene-editing is a potential therapeutic tool, however application to neurodegenerative disease models has been limited. Moreover, conventional mutation correction by would only be relevant for the small fraction of cases that are inherited. Here we introduce CRISPR/Cas9-based strategy in cell and animal edit endogenous amyloid precursor protein (APP) at extreme C-terminus reciprocally manipulate pathway, attenuating APP-β-cleavage Aβ production, while up-regulating neuroprotective APP-α-cleavage. APP N-terminus compensatory APP-homologues remain intact, with no apparent effects on neurophysiology vitro. Robust APP-editing seen human iPSC-derived neurons mouse brains detectable off-target effects. Our likely works limiting BACE-1 approximation, also delineate mechanistic events abrogates APP/BACE-1 convergence this setting. work offers conceptual proof selective silencing strategy.

Язык: Английский

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Alzheimer’s Disease: Mechanism and Approach to Cell Therapy

International Journal of Molecular Sciences, Год журнала: 2015, Номер 16(11), С. 26417 - 26451

Опубликована: Ноя. 4, 2015

Alzheimer’s disease (AD) is the most common form of dementia. The risk AD increases with age. Although two main pathological features AD, amyloid plaques and neurofibrillary tangles, were already recognized by Alois Alzheimer at beginning 20th century, pathogenesis remains unsettled. Therapeutic approaches targeting or tangles have not yet resulted in satisfactory improvements treatment. This may, part, be due to early-onset late-onset being underpinned different mechanisms. Most animal models are generated from gene mutations involved early onset familial accounting for only 1% all cases, which may consequently complicate our understanding In this article, authors discuss according neuropathologies, including senescence-related mechanisms possible treatments using stem cells, namely mesenchymal neural cells.

Язык: Английский

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Aerobic exercise improves quality of life, psychological well-being and systemic inflammation in subjects with Alzheimer’s disease

African Health Sciences, Год журнала: 2017, Номер 16(4), С. 1045 - 1045

Опубликована: Март 7, 2017

Background: Alzheimer's disease has a destructive drawbacks on the patient and his/her entire family as this badly affects behavior, cognition abilities to do activities of daily living (ADL). The physical mental benefits exercise are widely known but seldom available persons suffering from disease.Objective: aim study was measure quality life, systemic inflammation psychological well-being response aerobic exercises in Alzheimer's.Methods: Forty Alzheimer elderly subjects were enrolled two groups; first group received treadmill exercise, while second considered control no training intervention for months. Assessment tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), Rosenberg Self-Esteem Scale (RSES),Beck Depression Inventory (BDI), Profile Mood States(POMS) SF-36 health life (SF-36 HRQL) taken before at end study.Results: There 25.2%, 19.4%, 23.5%, 21.3%, 17.7% , 11.7%, 12.5% 10.1 % reduction mean values TNF-α, IL-6, BDI, POMS, transition subscale, bodily pain role functioning: emotional subscale respectively addition 15.7%, 13.1%, 12.6%, 11.1%, 13.2% 11.2 increase RSES, functioning functioning:physical general Vitality Social (A) training, so that there significant BDI & POMS HRQL scores, RSES result results (B) who not significant. Also, differences between levels investigated parameters (P<0.05).Conclusion: Treadmill walking is an effective treatment policy improve wellbeing Alzheimer's.Keywords: Aerobic well-being, inflammation,

Язык: Английский

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