Altered cellular distribution of phospho-tau proteins coincides with impaired retrograde axonal transport in neurons of aged rats

G Niewiadomska, M Baksalerska-Pazera, G Riedel

Research output: Book/ReportBook

36 Citations (Scopus)

Abstract

We hypothesize that the age-related degeneration of cytoskeleton in basal forebrain cholinergic neurons renders the NGF-TrkA signaling system non-functional and thereby impairs trophic support. Comparing young (4 months) and aged (28 months) rat brain, we examined immunohistochemically the compartmentalization of phosphorylated Tau protein using antibodies phospho-Tau404 and phospho-Tau231 of the GSK3 beta kinase, known to phosphorylate Tau, the neurotrophin NGF, and its receptor P-TrkA. Retrograde labeling of basal forebrain cholinergic cells after injection of fluorogold into multiple sites in cortex and hippocampus revealed a significantly lower number of fluorogold-positive cells in aged brain. Despite a lower density of P-TrkA immunoreactivity in cortex and hippocampus of aged rats, there was no difference in NGF expression. In young animals phospho-Tau404, phospho-Tau231, and GSK3 immunoreactivity was observed mainly in neuronal fibers with lower staining in somata both in cortex and hippocampus. By contrast, Tau and GSK3 labeling were confined to the cell bodies in aged rats. This is confirmation that aging leads to a redistribution of cytoskeletal proteins. Since a somatic localization of phospho-Tau is indicative of cytoskeletal breakdown, we suggest that failure of axonal trafficking may be responsible for the lack of trophic support in aged cholinergic neurons of the basal forebrain.

Original languageEnglish
PublisherUnknown Publisher
Number of pages9
DOIs
Publication statusPublished - 2005

Keywords

  • cholinergic system
  • NGF
  • Tau protein
  • hyperphosphorylation
  • axonal transport
  • neurodegeneration
  • aging
  • rat
  • NERVE GROWTH-FACTOR
  • SYNTHASE KINASE 3-BETA
  • ALZHEIMERS-DISEASE
  • NUCLEUS BASALIS
  • CHOLINERGIC NEURONS
  • MEYNERT
  • FOREBRAIN
  • RECEPTOR
  • NEURODEGENERATION

Cite this

Altered cellular distribution of phospho-tau proteins coincides with impaired retrograde axonal transport in neurons of aged rats. / Niewiadomska, G ; Baksalerska-Pazera, M ; Riedel, G .

Unknown Publisher, 2005. 9 p.

Research output: Book/ReportBook

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