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ISDN2012_0195: Influence of age on aluminum induced neurobehavioral, neurochemical and ultrastructural changes in rat brain: Protective role of donepezil HCl
Author(s) -
Tripathi Sandeep,
Choudhary Manisha,
Joshi Devesh K.,
Mahdi Abbas Ali,
Hasan Mahdi,
Mitra Kalyan
Publication year - 2012
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2012.10.020
Subject(s) - neurochemical , donepezil , medicine , context (archaeology) , biology , dementia , paleontology , disease
Sandeep Tripathi 1,∗, Manisha Choudhary 1, Devesh K. Joshi 1, Abbas Ali Mahdi 2, Mahdi Hasan 3, Kalyan Mitra 4 1 Department of Biotechnology, NIMS University, Jaipur (Raj) 303121, India 2 Department of Biochemistry, C.S.M. Medical University, Lucknow (UP) 226 003, India 3 Department of Anatomy, C.S.M. Medical University, Lucknow (UP) 226 003, India 4 Electron Microscopy Division, CDRI, Lucknow 226 001, India Aluminum exposure is known to be associated with oxidative stress and cognitive decline in experimental animals but the precise mechanism of its neurotoxicity has not yet been delineated. Evidence from clinical and animal model studies demonstrates that brain aluminum content increases with age. The donepezil HCl (DP) has been used extensively as neuropsychotic disorders. The present study attempts to assess the learning and memory capacity of rats using Y-maze test for cognitive functioning. The markers of oxidative stress, e.g. lipid peroxides and endogenous antioxidants as well as acetylcholinesterase (AChE) were measured in the hippocampus of young and aged rats fed with AlCl3 (100 mg/kg b.w.) for 90 days and normal saline treated controls. The other groups were treated AlCl3 along with 2.5 mg/kg b.w. donepezil HCl. We observed significant changes between Al treated young and aged rats and their controls in terms of lipid peroxides and endogenous antioxidants. Moreover, treatment with donepezil HCL restored the altered antioxidant enzyme activities and AChE when compared with experimental rats. Al treated groups exhibited significant changes in behavioral activity but it was reverses in DP treated group. Ultrastructural studies of the hippocampus of exposed rats revealed that the changes were more pronounced in the Al treated aged rats in terms of presence of spongiform lipofuscin, vacuolization and lysosomal degradation. Changes in synaptic morphology and decreased number of synapses were detected in the hippocampus of Al treated aged rats. Moreover, these changes were found to be restoring in DP treated groups. On the basis of the results, we safely conclude that Al may be linked with alteration in neurobehavioral and neurochemical changes and it may be responsible for the development of age related disorders. Moreover, DP may be used for the treatment of aluminum induced neurotoxicity.