Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adult
-
Aged, 80 and over
-
Animals
-
Calbindins
-
Choline O-Acetyltransferase / metabolism
-
Corpus Striatum / metabolism*
-
Corpus Striatum / pathology
-
Corpus Striatum / physiopathology
-
Disease Models, Animal
-
Disease Susceptibility / metabolism
-
Disease Susceptibility / physiopathology
-
Humans
-
Huntington Disease / metabolism*
-
Huntington Disease / pathology
-
Huntington Disease / physiopathology
-
Immunohistochemistry
-
Male
-
Middle Aged
-
Nerve Degeneration / metabolism*
-
Nerve Degeneration / pathology
-
Nerve Degeneration / physiopathology
-
Neurons / drug effects
-
Neurons / metabolism*
-
Neurons / pathology
-
Neurotoxins / pharmacology
-
Parvalbumins / metabolism
-
Proto-Oncogene Proteins c-bcl-2 / metabolism*
-
Proto-Oncogene Proteins c-myc / metabolism*
-
Quinolinic Acid / pharmacology
-
Rats
-
Rats, Sprague-Dawley
-
Reference Values
-
S100 Calcium Binding Protein G / metabolism
-
Tumor Suppressor Protein p53 / metabolism*
Substances
-
Calbindins
-
Neurotoxins
-
Parvalbumins
-
Proto-Oncogene Proteins c-bcl-2
-
Proto-Oncogene Proteins c-myc
-
S100 Calcium Binding Protein G
-
Tumor Suppressor Protein p53
-
Choline O-Acetyltransferase
-
Quinolinic Acid