Altered neurofilament protein expression in the lateral vestibular nucleus in Parkinson's disease

Exp Brain Res. 2017 Dec;235(12):3695-3708. doi: 10.1007/s00221-017-5092-3. Epub 2017 Sep 19.

Abstract

A major cause of morbidity in Parkinson's disease (PD) is postural instability. The neuropathology underlying postural instability is unknown. Postural control is mediated by Deiters' neurons of the lateral vestibular nucleus (LVN), which are the brainstem origin of descending vestibulospinal reflexes. Deiters' neurons express the cytostructural protein, non-phosphorylated neurofilament protein (NPNFP). In PD, reduced expression of NPNFP in substantia nigra (SN) neurons is believed to contribute to dysfunction. It was the aim of this study to determine if there is altered expression of NPNFP in the LVN in PD. We immunolabeled NPNFP in brainstem sections of six aged controls (mean age 92 yo) and six PD donors (mean age 83 yo). Our results show there was a ~ 50% reduction in NPNFP-positive Deiters' neurons compared to controls (13 ± 2.0/section vs 25.7 ± 3.0/section; p < 0.01, repeated measures ANOVA). In contrast, there was no difference in NPNFP-positive counts in the facial nucleus between control and PD. The normalized intensity of NPNFP labeling in LVN was also reduced in PD (0.87 ± 0.05 vs 1.09 ± 0.03; p < 0.01). There was a 35% concurrent reduction in NPNFP-positive neuropil in PD relative to controls (p < 0.01). We also show there was an 84% increase (p < 0.05) in somatic lipofuscin in PD patients compared to control. Lipofuscin aggregation has been shown to increase not only with age but also with neurodegeneration. Furthermore, decreased NPNFP intensity was strongly correlated with increasing lipofuscin autofluorescence across all cases (R 2 = 0.81, p < 0.01). These results show two alterations in cellular content with PD, reduced expression and intensity of NPNFP and increased lipofuscin aggregation in Deiter's neurons. These changes may contribute to degeneration of postural reflexes observed in PD.

Keywords: Lipofuscin; Neurodegeneration; Neurofilament; Parkinson’s disease; Postural instability; Vestibular.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autopsy
  • Female
  • Humans
  • Male
  • Neurofilament Proteins / metabolism*
  • Neurons / metabolism*
  • Neurons / pathology
  • Parkinson Disease / pathology*
  • Supranuclear Palsy, Progressive / pathology
  • Vestibular Nucleus, Lateral / metabolism*
  • Vestibular Nucleus, Lateral / pathology

Substances

  • Neurofilament Proteins