Curcumin Prevents Degeneration of Medial Septal Cholinergic Neurons Produced by Parkinsonism-Inducing Neurotoxin 1-Methyl-4-Phenylpyridinium

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is converted into the active metabolite 1-methyl-4-phenylpyridinium (MPP+), which damages dopamine (DA)-containing neurons of Substantia Nigra, and norepinephrine (NE)-containing neurons of Locus Coeruleus, thus mimicking the pathology of Parkinson’s disease (PD). In PD, cognitive impairment often occurs, which may be due to a loss of acetylcholine (ACh)-containing neurons within the basal forebrain. In turn, this may result from either direct damage to ACh neurons or indirect damage through loss of their DA and/or NE innervation. In the present study, we used neurons from the medial septal nucleus (MSN), which grow in the absence of DA or NE innervation, to assess the direct effects of MPP+ on MSN-derived ACh neurons. Administration of MPP+ directly damages MSN-derived neurons, as evidenced by neuronal loss and dramatic mitochondrial alterations. The phytochemical curcumin administered before MPP+ prevents ACh neuronal damage and mitochondrial derangement. Curcumin administration following MPP+ still promotes neuronal survival while reshaping both damaged mitochondria and cellular processes of ACh neurons. These latter effects are consistent with the expression of key proteins such as PINK1, Parkin, and LC3-II and activation of autophagy flux.