Implication of JAK1/STAT3/SOCS3 Pathway in Aging of Cerebellum of Male Rat: Histological and Molecular study

Sci Rep. 2020 Jun 1;10(1):8840. doi: 10.1038/s41598-020-64050-z.

Abstract

Aging causes morphological and functional changes in the cerebellum. This work aimed to demonstrate the implication of JAK1/STAT3/SOCS3 on aging-induced changes of rat cerebellum. Thirty male rats were divided into: adult (12 months), early senile (24 months) and late senile (32 months) groups. Immunohistochemical reaction of the cerebellum to GFAP and caspase-3 was assessed and the expression of JAK1, STAT3, SOCS3 proteins was also evaluated. TNFα as well as the activities of malondialdehyde (MDA) and reduced glutathione (GSH) in cerebellar tissue were also measured. The cerebellum of late senile rats revealed more degenerative changes than early senile rats in the form of increase in GFAP and caspase-3 immunoreaction. Additionally, there was decrease in JAK1and STAT3 expression in early and late senile rats and increase in SOCS3 when compare early and late senile groups with adult one. Enhancement of TNFα was noticed with aging as well as significant decrease in GSH and increase in MDA in early senile group. Moreover, late senile group revealed significant decrease in GSH and increase in MDA. It could be concluded that aging resulting in variable changes of the cerebellum as detected by morphological changes, immunohistochemical reactions of caspase-3 and GFAP and expression of JAK1/STAT3/SOCS3 proteins. Additionally, inflammatory marker TNFα and the activity of oxidative/antioxidative stress markers; malondialdehyde (MDA) and reduced glutathione (GSH) were also affected with aging.

MeSH terms

  • Aging*
  • Animals
  • Caspase 3 / metabolism
  • Cerebellum / metabolism*
  • Cerebellum / pathology
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutathione / metabolism
  • Immunohistochemistry
  • Janus Kinase 1 / metabolism*
  • Male
  • Malondialdehyde / metabolism
  • Microscopy, Electron
  • Rats
  • Rats, Wistar
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Suppressor of Cytokine Signaling 3 Protein / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • GFAP protein, rat
  • Glial Fibrillary Acidic Protein
  • STAT3 Transcription Factor
  • Suppressor of Cytokine Signaling 3 Protein
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Jak1 protein, rat
  • Janus Kinase 1
  • Caspase 3
  • Glutathione