Premium
Excitotoxic and metabolic damage to the rodent striatum: Role of the P75 neurotrophin receptor and glial progenitors
Author(s) -
Hanbury Rose,
Charles Vinod,
Chen ErYun,
Leventhal Liza,
Rosenstein Jeffrey M.,
Mufson Elliott J.,
Kordower Jeffrey H.
Publication year - 2002
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.10104
Subject(s) - biology , nestin , quinolinic acid , striatum , low affinity nerve growth factor receptor , neurotrophin , neuroscience , glial scar , lesion , microbiology and biotechnology , astrocyte , receptor , central nervous system , pathology , neural stem cell , stem cell , dopamine , medicine , tryptophan , biochemistry , amino acid
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 (p75 NTR ), 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 p75 NTR response, to define the conditions under which p75 NTR 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 p75 NTR receptor within the rat striatum at different survival times. Intrastriatal administration of QA between 7 days and 21 days postlesion induced p75 NTR expression in astrocytes that was preferentially distributed throughout the lesion core. P75 NTR 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, p75 NTR 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 p75 NTR immunoreactive elements resembled vasculature: but did not colocalize with the pan endothelium cell marker RecA‐1. In contrast, p75 NTR ‐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 p75 NTR 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 p75 NTR in structures related to progenitor cells. The expression of the p75 NTR 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. J. Comp. Neurol. 444:291–305, 2002. © 2002 Wiley‐Liss, Inc.