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1.
Mol Neurobiol ; 57(8): 3258-3272, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32514860

RESUMO

The complex multifactorial nature of AD pathogenesis has been highlighted by evidence implicating additional neurodegenerative mechanisms, beyond that of amyloid-ß (Aß) and tau. To provide insight into cause and effect, we here investigated the temporal profile and associations of pathological changes in synaptic, endoplasmic reticulum (ER) stress and neuro-inflammatory markers. Quantifications were established via immunoblot and immunohistochemistry protocols in post-mortem lateral temporal cortex (n = 46). All measures were assessed according to diagnosis (non-AD vs. AD), neuropathological severity (low (Braak ≤ 2) vs. moderate (3-4) vs. severe (≥ 5)) and individual Braak stage, and were correlated with Aß and tau pathology and cognitive scores. Postsynaptic PSD-95, but not presynaptic synaptophysin, was decreased in AD cases and demonstrated a progressive decline across disease severity and Braak stage, yet not with cognitive scores. Of all investigated ER stress markers, only phospho-protein kinase RNA-like ER kinase (p-PERK) correlated with Braak stage and was increased in diagnosed AD cases. A similar relationship was observed for the astrocytic glial fibrillary acidic protein (GFAP); however, the associated aquaporin 4 and microglial Iba1 remained unchanged. Pathological alterations in these markers preferentially correlated with measures of tau over those related to Aß. Notably, GFAP also correlated strongly with Aß markers and with all assessments of cognition. Lateral temporal cortex-associated synaptic, ER stress and neuro-inflammatory pathologies are here determined as late occurrences in AD progression, largely associated with tau pathology. Moreover, GFAP emerged as the most robust indicator of disease progression, tau/Aß pathology, and cognitive impairment.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/patologia , Estresse do Retículo Endoplasmático/fisiologia , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Biomarcadores/metabolismo , Encéfalo/metabolismo , Cognição/fisiologia , Disfunção Cognitiva/metabolismo , Feminino , Humanos , Inflamação/patologia , Masculino
2.
Sci Rep ; 7: 43890, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28262715

RESUMO

Citizen science projects have a long history in ecological studies. The research usefulness of such projects is dependent on applying simple and standardized methods. Here, we conducted a citizen science project that involved more than 3500 Swedish high school students to examine the temperature difference between surface water and the overlying air (Tw-Ta) as a proxy for sensible heat flux (QH). If QH is directed upward, corresponding to positive Tw-Ta, it can enhance CO2 and CH4 emissions from inland waters, thereby contributing to increased greenhouse gas concentrations in the atmosphere. The students found mostly negative Tw-Ta across small ponds, lakes, streams/rivers and the sea shore (i.e. downward QH), with Tw-Ta becoming increasingly negative with increasing Ta. Further examination of Tw-Ta using high-frequency temperature data from inland waters across the globe confirmed that Tw-Ta is linearly related to Ta. Using the longest available high-frequency temperature time series from Lake Erken, Sweden, we found a rapid increase in the occasions of negative Tw-Ta with increasing annual mean Ta since 1989. From these results, we can expect that ongoing and projected global warming will result in increasingly negative Tw-Ta, thereby reducing CO2 and CH4 transfer velocities from inland waters into the atmosphere.

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