Background Our previous studies demonstrated that cholinergic dysfunction occurred in transgenic mouse models and patients with Huntington's disease (HD). This may contribute to the cognitive deficits in the disease. Nerve growth factor (NGF) is an essential regulator of cholinergic neuronal survival and neurotransmission. We hypothesise that the cholinergic dysfunction may result from a failure of NGF availability and/or of retrograde NGF signalling.
Aim The project aimed to study whether administration of NGF could rescue cholinergic deficits in the models of HD.
Methods/techniques Intraventricular infusion. Star maze tests and immunohistochemistry.
Results Two weeks after intracerebroventricular NGF infusion, we performed behavioural tests using a starmaze setup, and injection of BrdU to assess cell proliferation and differentiation. The animals were killed 4 weeks after the NGF administration. Immunohistochemistry was performed. We observed significant improvement of the deteriorated spatial working memory in NGF treated R6/1 HD mice. Moreover, we unravel the underlying mechanisms by demonstrating a normalisation of cholinergic function and increased neurogenesis in the hippocampus of NGF treated R6/1 mice.
Conclusion The study provided rationales for early therapeutic intervention with NGF in HD.
- Huntington disease
- cholinergic function
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