Activated microglia proliferate at neurites of mutant huntingtin-expressing neurons.


Journal Article

In Huntington's disease (HD), mutated huntingtin (mhtt) causes striatal neurodegeneration which is paralleled by elevated microglia cell numbers. In vitro corticostriatal slice and primary neuronal culture models, in which neuronal expression of mhtt fragments drives HD-like neurotoxicity, were employed to examine wild type microglia during both the initiation and progression of neuronal pathology. As neuronal pathology progressed, microglia initially localized in the vicinity of neurons expressing mhtt fragments increased in number, demonstrated morphological evidence of activation, and expressed the proliferation marker, Ki67. These microglia were positioned along irregular neurites, but did not localize with mhtt inclusions nor exacerbate mhtt fragment-induced neurotoxicity. Prior to neuronal pathology, microglia upregulated ionized calcium binding adaptor molecule 1 (Iba1), signaling a functional shift. With neurodegeneration, interleukin-6 and complement component 1q were increased. The results suggest a stimulatory, proliferative signal for microglia present at the onset of mhtt fragment-induced neurodegeneration. Thus, microglia effect a localized inflammatory response to neuronal mhtt expression that may serve to direct microglial removal of dysfunctional neurites or aberrant synapses, as is required for reparative actions in vivo.

Full Text

Cited Authors

  • Kraft, AD; Kaltenbach, LS; Lo, DC; Harry, GJ

Published Date

  • March 2012

Published In

Volume / Issue

  • 33 / 3

Start / End Page

  • 621.e17 - 621.e33

PubMed ID

  • 21482444

Pubmed Central ID

  • 21482444

Electronic International Standard Serial Number (EISSN)

  • 1558-1497

International Standard Serial Number (ISSN)

  • 0197-4580

Digital Object Identifier (DOI)

  • 10.1016/j.neurobiolaging.2011.02.015


  • eng