Excitotoxic and metabolic damage to the rodent striatum: Role of the p75 neurotrophin receptor and glial progenitors

Rose Hanbury, Vinod Charles, Er Yun Chen, Liza Leventhal, Jeffrey M. Rosenstein, Elliott J. Mufson, Jeffrey H. Kordower

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


After injury, the striatum displays several morphologic responses that may play a role in both regenerative and degenerative events. One such response is the de novo expression of the low-affinity p75 neurotrophin receptor (p75NTR), a gene that plays critical roles in central nervous system (CNS) cell death pathways. The present series of experiments sought to elucidate the cellular origins of this p75NTR response, to define the conditions under which p75NTR is expressed after striatal injury, and how this receptor expression is associated with neuronal plasticity. After chemical lesions, by using either the excitotoxin quinolinic acid (QA) or the complex II mitochondria inhibitor 3-nitropropionic acid (3-NP), we compared the expression of the p75NTR receptor within the rat striatum at different survival times. Intrastriatal administration of QA between 7 days and 21 days postlesion induced p75NTR expression in astrocytes that was preferentially distributed throughout the lesion core. P75NTR immunoreactivity within astrocytes was seen at high (100-220 nmol) but not low (50 nmol) QA doses. Seven and 21 days after 3-NP lesions, p75NTR expression Was present in astrocytes at all doses tested (100-1, 000 nmol). However, in contrast to QA, these cells were located primarily around the periphery of the lesion and not within the lesion core. At the light microscopic level p75NTR immunoreactive elements resembled vasculature: But did not colocalize with the pan endothelium cell marker RecA-1. In contrast, p75NTR-containing astrocytes colocalized with nestin, vimentin, and 5-bromo-2-deoxyuridine, indicating that these cells are newly born astrocytes. Additionally, striatal cholinergic neurons were distributed around the lesion core expressed p75NTR 3-5 days after lesion in both QA and 3-NP lesions. These cells did not coexpress the pro-apoptotic degradation enzyme caspase-3. Taken together, these data indicate that striatal lesions created by means of excitotoxic or metabolic mechanisms trigger the expression of p75NTR in structures related to progenitor cells. The expression of the p75NTR receptor after these chemical lesions support the concept that this receptor plays a role in the initiation of endogenous cellular events associated with CNS injury.

Original languageEnglish (US)
Pages (from-to)291-305
Number of pages15
JournalJournal of Comparative Neurology
Issue number4
StatePublished - Mar 18 2002
Externally publishedYes


  • 3-nitropropionic acid
  • 5-bromo-2-deoxyuridine (BrdU)
  • GFAP
  • Mitochondrial dysfunction
  • Nestin
  • Neurodegeneration
  • Quinolinic acid
  • Vimentin

ASJC Scopus subject areas

  • General Neuroscience


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