Loss of Collapsin Response Mediator Protein 4 Attenuates 6-Hydroxydopamine-Induced Impairments in a Mouse Model of Parkinson's Disease

Neurochem Res. 2020 Oct;45(10):2286-2301. doi: 10.1007/s11064-020-03086-z. Epub 2020 Jul 9.

Abstract

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by impaired motor symptoms induced by the degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc). Many factors are speculated to operate in the mechanism of PD, including oxidative stress, mitochondrial dysfunction, abnormal protein handling, and PD induced apoptosis. Besides, researchers have recently shown that inflammatory secretions may engage neighboring cells such as astrocytes, which then induce autocrine and paracrine responses that amplify the inflammation, leading to neurodegeneration. In the present study, we analyzed the neuroprotective and anti-inflammatory effects of collapsin response mediator protein 4 (CRMP4) deletion in 6-hydroxydopamine (6-OHDA)-injected male mice, as well as its effects on motor impairments. Our findings indicated that the deletion of CRMP4 could maintain the TH-positive fibers in the striatum and the TH-positive cells in SNc, attenuate the inflammatory responses, and improve motor coordination and rotational behavior. Furthermore, based on our findings at the early time points, we hypothesized that primary differences between the Crmp4+/+ and Crmp4-/- mice may occur in microglia instead of neurons. Although further work should be carried out to clarify the specific role of CRMP4 in the pathogenesis of PD, our findings suggest that it could be a possible target for the treatment of PD.

Keywords: Mouse model; Neurodegeneration; Neuroinflammation; Parkinson's disease.

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Dopaminergic Neurons / metabolism
  • Gene Deletion
  • Genetic Therapy
  • Male
  • Mice
  • Microglia / metabolism
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • Oxidopamine
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / therapy*
  • Pars Compacta / metabolism
  • Psychomotor Disorders / genetics
  • Psychomotor Disorders / therapy
  • Psychomotor Performance / drug effects

Substances

  • Crmp-4 protein, mouse
  • Nerve Tissue Proteins
  • Oxidopamine
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Casp3 protein, mouse
  • Caspase 3