engleski

Cerebellum in Alzheimer's disease: quercetin as a potential therapeutic

The cerebellum is a relatively neglected area of the Alzheimer's disease (AD) brain, probably because it was formerly thought to be spared by the disease. However, a number of pathological changes have now been revealed in the AD cerebellum, principally by immunocytochemical studies, including widespread deposits of diffuse amyloid. Diffuse plaques, also called benign plaques, occur much earlier than neuritic plaques, thus supporting the idea of a therapeutic intervention in the early stage of the disease. The aetiological mechanisms underlying the neuropathological changes in AD still remain unclear but are probably affected by environmental, genetic, and neuroinflammatory factors. This study was aimed to explore neuroprotective role of quercetin as potential therapeutic in the early stage of induced AD. Three-months-old male (n=10) highly inbred Y59 strain rats were intraperitoneally administered with: (a) 0.9% NaCl, HC control group ; (b) AlCl3 (10 mg/kg) and D-(+)- galactose (60 mg/kg), AD group ; (c) AlCl3 (10 mg/kg) and D-(+)- galactose (60 mg/kg) and quercetin (50 mg/kg), AD+Qu50 ; (d) quercetin (50 mg/kg), Qu50, per day consecutively for 28 days. The brain samples were prepared according to standard paraffin procedure. Sections of 7- 10 microns were stained with hematoxylin- eosin and modified Bielschowsky, comparable areas were analyzed by light microscopy. Changes related to neurodegenerative damage were analyzed by immunohistochemistry using the following primary monoclonal antibodies: purified (azide free) anti- β-amyloid, 17-24 (Clone: 4G8) ; CD68 (E-11) ; anti-phospho-PHF- tau pSer202/Thr205 (AT8) ; anti- tau pSer396/404 (PHF1) and Tau-001 (MC1). Diffuse cerebellar plaques were recognized by antibody 4G8 in AD and AD+Qu50 (reduced number of plaques) group, but neither tau- immunoreactive neurofibrillary tangles nor reactive astrocytes / microglial cells were seen. The results obtained suggest sensitivity of the brain to low doses of aluminium chloride and neuroprotective role of quercetin as a potential therapeutic agent in the early stage of AD.

cerebellum, Alzheimer's disease, quercetin, therapeutic, histology

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