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Impairment of the septal cholinergic neurons in MPTP-treated A30P α-synuclein mice

Lookup NU author(s): Professor Tiago Outeiro

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Abstract

Dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) are characterized by loss of acetylcholine (ACh) from cortical areas. Clinical studies report positive effects of acetylcholine esterase (AChE) inhibitors in PDD and dementia with Lewy bodies. We here report that the number of neurons expressing a cholinergic marker in the medial septum-diagonal band of Broca complex decreases in A30P α-synuclein-expressing mice during aging, paralleled by a lower AChE fiber density in the dentate gyrus and in the hippocampal CA1 field. After inducing dopamine depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), no acute but a delayed loss of cholinergic neurons and AChE-positive fibers was observed, which was attenuated by L-3,4-dihydroxyphenylalanine (DOPA) treatment. Expression of nerve growth factor (NGF) and tyrosine receptor kinase A (TrkA) genes was upregulated in 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride-treated wild type mice, but not in A30P α-synuclein expressing animals. In contrast, upregulation of sortilin and p75NTR genes was found in the A30P α-synuclein-expressing mice. These results suggest that dopamine deficiency may contribute to the impairment of the septohippocampal system in patients with PDD and that L-3,4-dihydroxyphenylalanine may not only result in symptomatic treatment of the akinetic-rigid syndrome but may also alleviate the degeneration of basal forebrain cholinergic system and the cognitive decline. © 2013 Elsevier Inc.


Publication metadata

Author(s): Szego EM, Outeiro TF, Kermer P, Schulz JB

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2013

Volume: 34

Issue: 2

Pages: 589-601

Print publication date: 11/05/2012

Online publication date: 21/04/2012

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier

URL: https://doi.org/10.1016/j.neurobiolaging.2012.04.012

DOI: 10.1016/j.neurobiolaging.2012.04.012

PubMed id: 22579457


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