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P2‐110: Environmental Enrichment–Induced Cognitive Enhancement Through Transient Receptor Potential‐Canonical 1
Author(s) -
Wang Lin,
Zhou Xinwen
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1316
Subject(s) - long term potentiation , hippocampal formation , transient receptor potential channel , western blot , synaptic plasticity , trpc1 , creb , environmental enrichment , neuroscience , morris water navigation task , medicine , endocrinology , biology , chemistry , psychology , receptor , biochemistry , transcription factor , gene
clinical dementia rating (CDR) cognitive scores were also conducted. Results: OAb, phospho-Tau, conformational-Tau and oligomeric-Tau were robustly elevated in AD cf. Non-AD cases, as were inflammatory markers (p<0.05-0.001) while synaptophysin and PSD-95 levels decreased (AD cf. Non-AD, p<0.05). Pathological Tau species tracked disease severity (p<0.05-0.01) and demonstrated strong correlations across Braak stages (p<0.05-0.01, R>0.6). Critically, OAb also reported high correlations with progressive Braak stages (p<0.01, R1⁄40.9), yet only when quantified in non-denaturing protocols. Decreased PSD-95 and increased GFAP levels did not correlate with Braak stages, despite their significant in cases of late stage pathology (Braak 5-6 cf. Braak 0-2, p<0.05). ER stress markers did not overall discriminate between AD vsNon-AD groups, however a strong correlation between phospho-PERK and IRE1 with Braak stages (p<0.05, R>0.6) was observed alongside an increase in BIP/GRP78 levels in cases of moderate pathology (Braak 3-4 cf. 0-2, p<0.05). Importantly, both Tau makers as well as OAb, when in a non-denatured state, strongly correlated with cognitive decline, while phospho-PERK and GFAP demonstrated modest associations. Conclusions: This study provides a comprehensive profile of multiple pathological processes in individual AD cases. Our data highlight disease relevant species, particularly native OAb and Tau, and supports the involvement of ER stress in the pathological process of AD and cognitive deterioration.