Susceptibility of striatal neurons to excitotoxic injury correlates with basal levels of Bcl-2 and the induction of P53 and c-Myc immunoreactivity.
The present studies evaluated the potential contribution of Bcl-2, p53, and c-Myc to the differential vulnerability of striatal neurons to the excitotoxin quinolinic acid (QA). In normal rat striatum, Bcl-2 immunoreactivity (Bcl-2-i) was most intense in large aspiny interneurons including choline acetyltransferase positive (CAT+) and parvalbumin positive (PARV+) neurons, but low in a majority of medium-sized neurons. In human brain, intense Bcl-2-i was seen in large striatal neurons but not in medium-sized spiny projection neurons. QA produced degeneration of numerous medium-sized neurons, but not those enriched in Bcl-2-i. Many Bcl-2-i-enriched interneurons including those with CAT+ and PARV+ survived QA injection, while medium-sized neurons labeled for calbindin D-28K (CAL D-28+) did not. In addition, proapoptotic proteins p53-i and c-Myc-i were robustly induced in medium-sized neurons, but not in most large neurons. The selective vulnerability of striatal medium spiny neurons to degeneration in a rodent model of Huntington's disease appears to correlate with their low levels of Bcl-2-i and high levels of induced p53-i and c-Myc-i.
Liang
Zhong-Qin
ZQ
Department of Pharmacology, Soochow University School of Medicine, Suzhou 215007, P.R. China.
Wang
Xiao-Xia
XX
Wang
Yumei
Y
Chuang
De-Maw
DM
DiFiglia
Marian
M
Chase
Thomas N
TN
Qin
Zheng-Hong
ZH
D000328:Adult; D000369:Aged, 80 and over; D000818:Animals; D064026:Calbindins; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology; D010320:Parvalbumins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D064026:Calbindins; D009498:Neurotoxins; D010320:Parvalbumins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D064030:S100 Calcium Binding Protein G; D016159:Tumor Suppressor Protein p53; D002795:Choline O-Acetyltransferase; D017378:Quinolinic Acid