The effects of α-synuclein oligomers on neurogenesis in the hippocampus and the behavior of aged mice

Abstract

We studied the effects of intranasal administration of oligomeric forms of the α-synuclein protein, which plays an important role in the pathogenesis in a group of chronic neurodegenerative diseases, that is, synucleinopathies. Neurogenesis in the hippocampus, the number of dopaminergic neurons in the substantia nigra, locomotor and orienting-exploratory activity, learning and memory, and the emotional state were studied in aged animals. Twelve-month-old male C57Bl/6 mice were used for the experiments. The solution of oligomers of α-synuclein was administered daily to mice for 14 days. The behavioral testing included the open-field test, novel-object recognition, passive avoidance conditioning, and the elevated plus-maze. Proliferating cells, immature neurons, and dopaminergic neurons were detected using immunohistochemical staining with antibodies to the bromodeoxyuridine, doublecortin, and tyrosine hydroxylase markers. We found that α-synuclein oligomers induced a significant increase in the number of proliferating cells and immature neurons in the hippocampal dentate gyrus and a decrease in the number of dopaminergic neurons in the substantia nigra pars compacta. The treated mice exhibited decreased locomotor and orienting-exploratory activities, impaired formation and retrieval of episodic memory, and increased anxiety. Our data show that the non-motor behavioral effects of α-synuclein oligomers may be related to impairments in hippocampal neurogenesis and may be considered as experimental evidence of the involvement of postnatal neurogenesis in the development of synucleinopathies.