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P4‐263: Angiotensin receptors blockers could be associated with a lower MMSE score decline in hypertensive patients with Alzheimer's disease
Author(s) -
Lu Clara,
Mackowiak MarieAnne,
Richard Florence,
Pasquier Florence
Publication year - 2011
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.2011.05.2300
Subject(s) - medicine , angiotensin receptor blockers , disease , antihypertensive drug , blood pressure , medical prescription , alzheimer's disease , cardiology , pharmacology , angiotensin converting enzyme
mg/kg) or vehicle was intragastrically administered once daily to rats with bilateral FFT, starting immediately after the surgery and lasting for 4 weeks. The learning and memory abilities were measured byMorris water maze and step-through tests. Pathological change was evaluated with Nissl’s staining on cerebral cortex and hippocampus. Protein expression of neurotrophic factors, growth-associated protein (GAP43), Nogo A and Chondroitin Sulfate Proteoglycan (CSPG) was detected by immunohistochemistry and Western blot. The expression of apoptosisregulating factors was detected by Western blot. Results: Morris water maze and stepthrough tests showed that the memory deficits seen in FFT rats were significantly improved by CIG treatment. Immunohistochemical analysis showed that CIG treatment attenuated the loss of neurons in hippocampal cornu ammonis (CA) 1 region and dentate gyrus (DG). FFT reduced hippocampal protein levels of nerve growth factor (NGF), tyrosine receptor kinase A (Trk A), brain-derived neurotrophic factor (BDNF), synaptophysin (SYP) and B-cell lymphoma-2 (Bcl-2), but not levels of tyrosine receptor kinase B (Trk B) and GAP-43. FFT also elevated Nogo A, CSPG, cytochorome C (Cyt c) and bcl-2-Associated X Protein (Bax). Administration of CIG to FFT rats significantly elevated the expression of NGF, TrkA, BDNF, SYP, GAP-43 and Bcl-2, and decreased the expression of Nogo A, CSPG, Cyt c and Bax. Conclusions: These results indicated that CIG effectively counteracted cognitive impairments caused by fimbria-fornix lesions, and the mechanisms might be related to promoting neuronal survival and providing a beneficial microenvironment for central nerve regeneration and repair. Thus, CIG may have strong potentials for treating AD.