Abstract
Cognitive dysfunction can be common among Parkinson's disease (PD) patients, and multiplication
of the gene α-synuclein (αsyn) increases the risk of dementia. Here, we studied the
role of dopamine-depletion and increased αsyn load and aggregation on cholinergic
structures in vivo. Wild-type (WT) and mice with A30P αsyn overexpression were treated subacutely with
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and the number of cholinergic
cells in their nucleus basalis magnocellularis-substantia innominata (NBM-SI), their
cortical fiber density and their expression of different genes 1 day or 90 days after the last MPTP-injection were measured. Long-term dopamine depletion decreased
the expression of choline acetyl transferase (ChAT) in the NBM-SI of WT mice, but
no neuron loss was observed. In contrast, cortical cholinergic fiber density was decreased
three months after MPTP-injection. Increased brain-derived neurotrophic factor expression
could maintain cholinergic functions under these conditions. Expression of A30P αsyn
in six-months-old transgenic mice resulted in decreased tyrosine receptor kinase B
expression, and lower cortical cholinergic fiber density. Dopamine-depletion by MPTP
induced cholinergic cell loss in the NBM-SI and increased cortical fiber loss. Our
findings may explain why cholinergic cells are more vulnerable in PD, leading to an
increased probability of dementia.
Keywords
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Article info
Publication history
Published online: July 20, 2011
Accepted:
June 26,
2011
Received in revised form:
May 23,
2011
Received:
March 15,
2011
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
