Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson’s disease

Zhaoxiang Zhou,Qi-Yu Chen,Penghai Ye,Weiqi Liu,Jing-Shan Lu,Lin Lu,Wantong Shi,Muhang Li,Xu-Hui Li,Yanan Li,Ping-Yi Xu,Yuxiang Zhang,Man Xue,Min Zhuo

doi:10.1186/s13041-021-00870-y

Abstract

Parkinson’s disease (PD) is a multi-system neurodegenerative disorder. Patients with PD often suffer chronic pain. In the present study, we investigated motor, sensory and emotional changes in three different PD mice models. We found that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treatment caused significant changes in all measurements. Mechanical hypersensitivity of PD model induced by MPTP peaked at 3 days and persisted for at least 14 days. Using Fos transgenic mice, we found that neurons in the anterior cingulate cortex (ACC) were activated after MPTP treatment. Inhibiting ACC by bilateral microinjection of muscimol significantly reduced mechanical hypersensitivity and anxiety-like responses. By contrast, MPTP induced motor deficit was not affected, indicating ACC activity is mostly responsible for sensory and emotional changes. We also investigated excitatory synaptic transmission and plasticity using brain slices of MPTP treated animals. While L-LTP was blocked or significantly reduced. E-LTP was not significantly affected in slices of MPTP treated animals. LTD induced by repetitive stimulation was not affected. Furthermore, we found that paired-pulse facilitation and spontaneous release of glutamate were also altered in MPTP treated animals, suggesting presynaptic enhancement of excitatory transmission in PD. Our results suggest that ACC synaptic transmission is enhanced in the animal model of PD, and cortical excitation may play important roles in PD related pain and anxiety.

Highlights

Parkinson’s disease (PD) is a neurodegenerative disease classically characterized by motor dysfunction [1]
PD models induced by MPTP, 6‐OHDA, and A53T transgenic mice Since the main symptoms of PD are motor deficits, we performed the RotaRod test, grip strength test, homecage behavior recording, and open field test, which are commonly used to confirm the phenotypes of PD model animals
Motor function was assessed by RotaRod test, grip strength test, and open field test, which significantly declined after MPTP or 6-Hydroxydopa‐ mine (6-OHDA) administration, but not in A53T transgenic mice (Fig. 1a–-d)

Summary

Introduction

Parkinson’s disease (PD) is a neurodegenerative disease classically characterized by motor dysfunction [1]. In addition to the motor symptoms, the non-motor symptoms of PD such as pain and anxiety, are gaining more clinical attention [2]. There are 30–95% of patients with PD suffering from different forms of pain, including acute pain and chronic pain [3]. Most of previous PD basic studies mainly focused on midbrain dopaminergic neurons [7], less is known about the ACC. The anterior cingulate cortex (ACC) is a key cortical region in pain perception, chronic pain and emotional anxiety and fear [8,9,10]. Excitatory synaptic transmission in the ACC undergo both pre- and postsynaptic long-term potentiation (LTP) in different animal

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Results

Discussion

Conclusion