Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study the changes in central and peripheral immunity in PD, the advantages and limitations of the techniques, and their applicability to humans. Although a single animal model cannot replicate all pathological features of the human disease, neuroinflammation is present in most animal models of PD and plays a critical role in understanding the involvement of the immune system (IS) in the pathogenesis of PD. The IS and its interactions with different cell types in the central nervous system (CNS) play an important role in the pathogenesis of PD. Even though culture models do not fully reflect the complexity of disease progression, they are limited in their ability to mimic long-term effects and need validation through in vivo studies. They are an indispensable tool for understanding the interplay between the IS and the pathogenesis of this disease. Understanding the immune-mediated mechanisms may lead to potential therapeutic targets for the treatment of PD. We believe that the development of methodological guidelines for experiments with animal models and PD patients is crucial to ensure the validity and consistency of the results.

Activation of Pedunculopontine Tegmental Nucleus Alleviates the Pain Induced by the Lesion of Midbrain Dopaminergic Neurons

“…Notably, the underlying mechanisms of pain or altered pain perception in PD are not fully understood, hindering its effective treatment. PD is characterized by the loss of midbrain dopaminergic (DA) neurons, indicating that a decrease in DA neurons disinhibits pain signals in PD patients [ 6 , 8 , 9 ]. However, the therapeutic efficacy of dopamine drugs in relieving pain symptoms associated with PD has been reported to be inconsistent [ 10 , 11 ], suggesting an urgent need to explore new treatment strategies.…”

“…Based on these considerations, we hypothesized that PD pain is mainly due to the loss of midbrain DA neurons. In this study, we established a mouse model of DA lesion-induced pain by unilaterally injecting 6-hydroxydopamine (6-OHDA) into the midbrain dopamine regions [ 9 , 18 ]. Subsequently, we tested whether the chemogenetic activation of the PPTg could ameliorate pain hypersensitivity in 6-OHDA-lesioned mice.…”