&nbsp;Roscovitine rescuing neuronal loss and neuroinflammation in brain regions associated with Parkinson’s disease mice

LIU Ye; CHU Ya-Nan; XU Cen-Lu; HE Jia-Cheng; SU Bing-Yin; TAI Hao-Ran

doi:10.16098/j.issn.0529-1356.2023.06.003

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Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (6) : 635-643. DOI: 10.16098/j.issn.0529-1356.2023.06.003

Neurobiology

Roscovitine rescuing neuronal loss and neuroinflammation in brain regions associated with Parkinson’s disease mice

LIU Ye¹ CHU Ya-nan¹,2 XU Ce-lu¹ HE Jia-cheng¹ SU Bing-yin^{1,2 *} TAI Hao-ran^1,2*

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Abstract

Objective To investigate the effect and possible mechanism of cell cycle-dependent kinase (Cdk)5 inhibitor Roscovitine on 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced pathological changes in brain regions associated with Parkinson’s disease (PD) model mice. Methods The effect of Roscovitine on the relative expression levels of P25 and Cdk5 proteins was detected by Western blotting in MPP+-treated cells. The ELISA method detected the effect of Roscovitine on the release of dopamine. Fifteen male C57BL/6N mice were randomly divided into 3 groups, PBS group, MPTP group, and MPTP + Roscovitine group, 5 mice in each group. PD model mice were prepared by intraperitoneal injection of 25 mg/(kg ·d) MPTP for 7 consecutive days from the 3rd day in the MPTP + Roscovitine group, and 10 mg/(kg ·d) Roscovitine was injected intraperitoneally for 10 days in the MPTP + Roscovitine group, and the PBS group was given the same volume of PBS. Twenty-four hours after the last dose, the effect of Roscovitine on the behavior of PD model mice was detected by gait analysis, open field experiment, and rod rotation experiment. The effect of Roscovitineon the expression of neurons, glial cells, neuroinflammation and other related indexes in PD model mice such as nigrostriatal tyrosine hydrogenase (TH) and PD-related brain regions was detected by immunohistochemistry. Results Western blotting and ELISA showed that the expression levels of P25 and Cdk5 proteins and the release of dopamine decreased relatively low in MPP+ treated cells (P<0.01), Roscovitine could reduce the expression level of P25 and Cdk5 protein (P<0.05), increased the release of dopamine (P< 0.05）; Compared with the PBS group, the PD model mice in the MPTP group had motor dysfunction and decreased the number of TH+ cells in the substantia nigra and striatum (P< 0.01). The number of positive cells in PD-related brain regions increased in glial fibrillary acidic protein (GFAP), Iba1, inhibitor of nuclear factor kappa B (NF-κB) kinase subunit α(IKKα), and p-IKK (P<0.05), and Roscovitine intervention significantly improved exercise capacity (P<0.01), increased TH(P<0.01), reduced GFAP, Iba1, IKKα, p-IKK (P< 0.05). Conclusion Roscovitine can reduce the loss of dopaminergic neurons and glial cell activation in PD-related brain regions of MPTP model mice, and inhibit the activation of NF-κB signaling pathway, thereby exerting neuroprotective effects.

Key words

Parkinson’s disease

/ 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / cyclin-dependent kinase 5 / Roscovitine / Immunohisochemistry / Mouse

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LIU Ye CHU Ya-nan XU Ce-lu HE Jia-cheng SU Bing-yin TAI Hao-ran. Roscovitine rescuing neuronal loss and neuroinflammation in brain regions associated with Parkinson’s disease mice[J]. Acta Anatomica Sinica. 2023, 54(6): 635-643 https://doi.org/10.16098/j.issn.0529-1356.2023.06.003

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