Aging causes morphological alterations in astrocytes and microglia in human substantia nigra pars compacta

Neurobiol Aging. 2015 Dec;36(12):3321-3333. doi: 10.1016/j.neurobiolaging.2015.08.024. Epub 2015 Aug 31.

Abstract

Age being a risk factor for Parkinson's disease, assessment of age-related changes in the human substantia nigra may elucidate its pathogenesis. Increase in Marinesco bodies, α-synuclein, free radicals and so forth in the aging nigral neurons are clear indicators of neurodegeneration. Here, we report the glial responses in aging human nigra. The glial numbers were determined on Nissl-stained sections. The expression of glial fibrillary acidic protein, S100β, 2', 3'-cyclic nucleotide 3' phosphodiesterase, and Iba1 was assessed on cryosections of autopsied midbrains by immunohistochemistry and densitometry. The glial counts showed a biphasic increase, of which, the first prominent phase from fetal age to birth could be physiological gliogenesis whereas the second one after middle age may reflect mild age-related gliosis. Astrocytic morphology was altered, but glial fibrillary acidic protein expression increased only mildly. Presence of type-4 microglia suggests possibility of neuroinflammation. Mild reduction in 2', 3'-cyclic nucleotide 3' phosphodiesterase-labeled area denotes subtle demyelination. Stable age-related S100β expression indicates absence of calcium overload. Against the expected prominent gliosis, subtle age-related morphological alterations in human nigral glia attribute them a participatory role in aging.

Keywords: Autopsied human midbrains; CNPase; Densitometry; GFAP; Iba1; Morphometry; Parkinson's disease; S100β; Stereology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / metabolism
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / pathology*
  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Calcium / metabolism
  • Child
  • Child, Preschool
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Infant
  • Male
  • Microglia / metabolism
  • Microglia / pathology*
  • Middle Aged
  • Nerve Degeneration*
  • Neurogenic Inflammation
  • Parkinson Disease
  • Pars Compacta / cytology*
  • Pars Compacta / pathology*
  • Risk Factors
  • S100 Calcium Binding Protein beta Subunit / metabolism
  • Young Adult

Substances

  • Glial Fibrillary Acidic Protein
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase
  • Calcium