Acute MPTP treatment decreases dendritic spine density of striatal medium spiny neurons via SNK-SPAR pathway in C57BL/6 mice

Abstract

Parkinson's disease (PD) is a well-known neurodegenerative disorder associated with a high risk in middle-aged and elderly individuals, severely impacting the patient's quality of life. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is frequently used to establish PD in animals. Dendritic spines are dendritic processes that form the foundation of learning and memory. Reportedly, dendritic spine density of striatal medium spiny neurons (MSNs) declines in PD, and this decline has been associated with PD progression; however, the underlying mechanism remains elusive. Herein, we used the MPTP animal model to examine whether serum-induced kinase (SNK) and spine-associated Rap guanosine triphosphatase (SPAR) contribute to decreased dendritic spine density in striatal MSNs. MPTP was used to establish the animal model, which exhibits motor function impairment and dopaminergic cell loss. To assess spine density, Golgi staining was performed to count striatal dendritic spines, which were reduced in the MPTP group when compared with those in the normal control group. Immunohistochemistry was performed to analyze changes in SNK and SPAR expression. MPTP treatment significantly increased the expression of SNK in striatal MSNs, whereas that of SPAR was significantly decreased when compared with the normal control group. These findings offer clues to further explore the mechanism of declining dendritic spine density in patients with PD and provide evidence for potential target identification in PD.

Keywords: MPTP; MSNs; PD; SNK; SPAR; dendritic spine density.