Dopamine-depletion and increased alpha-synuclein load induce degeneration of cortical cholinergic fibers in mice

作者：Szego Eva M^*; Gerhardt Ellen; Outeiro Tiago F; Kermer Pawel

来源：Journal of the Neurological Sciences, 2011, 310(1-2): 90-95.

DOI：10.1016/j.jns.2011.06.048

• MPTP
• Cholinergic
• Nucleus basalis magnocellularis
• BDNF
• TrkB
• Dopamine

Cognitive dysfunction can be common among Parkinson's disease (PD) patients, and multiplication of the gene alpha-synuclein (alpha syn) increases the risk of dementia. Here, we studied the role of dopamine-depletion and increased asyn load and aggregation on cholinergic structures in vivo. Wild-type (WT) and mice with A30P asyn overexpression were treated subacutely with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MFTP), 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 alpha syn 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.

• 出版日期2011-11-15