Restoration of Memory Along With Neurogenic Enhancement by Therapeutic Botulinum Neurotoxin in a Preclinical Model of Parkinson’s Disease

Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra (SN), leading to motor impairments, while hippocampal dysfunction contributes to memory deficits. Botulinum neurotoxin (BoNT), a therapeutic modulator of acetylcholine (ACh) release, its cognitive effects remain underexplored. We investigated the effect of BoNT on spatial learning, memory, microglia and hippocampal neurogenesis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Behavioral tests, including the open field, novel object recognition, and Morris water maze, demonstrated significant improvements in locomotion, learning, and memory with BoNT treatment. BoNT increased the number of doublecortin (DCX)-positive immature neurons and percentage of bromodeoxyuridine (BrdU)/neuronal nuclei (NeuN) double-positive cells, while the reduced number of microglia was evident in the hippocampal dentate gyrus (DG). Additionally, histological analyses revealed BoNT-mediated protection of pyramidal neurons in hippocampal cornu ammonis (CA)-1 and CA3 regions. These findings suggest that BoNT mitigates memory deficits by promoting neurogenesis in experimental PD.