Increased calbindin-D28k immunoreactivity in striatal projection neurons of R6/2 Huntington's disease transgenic mice

Z. Sun, H. B. Wang, Yunping Deng, W. L. Lei, J. P. Xie, C. A. Meade, N. Del Mar, D. Goldowitz, Anton Reiner

Research output: Contribution to journalArticle

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Abstract

Striatal degeneration in Huntington's disease (HD) is associated with increases in perikaryal calbindin immunolabeling in yet-surviving striatal projection neurons. Since similar increases have also been observed in surviving striatal projection neurons after intrastriatal injection of the excitotoxin quinolinic acid, the increased calbindin in HD striatum has been interpreted to suggest an excitotoxic process in HD. We used immunolabeling to assess if calbindin is elevated in striatal projection neurons of R6/2 HD transgenic mice. These mice bear exon 1 of the human huntingtin gene with 144 CAG repeats and show some of the neuropathological signs (e.g., neuronal intranuclear inclusions) and clinical traits (e.g., wasting prior to early death) of HD. We found an increased frequency of calbindin-immunoreactive neuronal perikarya in the striatum of 6- and 12-week-old R6/2 mice compared to wild-type controls. This increase was most notable in the normally calbindin-poor dorsolateral striatum. We found no significant changes in the total area of striatum occupied by the calbindin-negative striosomes and no consistent changes in striatal calbindin mRNA. The increase in calbindin in R6/2 striatal neurons was thus limited to the matrix compartment, and it may be triggered by increased Ca 2+ entry due to the demonstrated heightened NMDA sensitivity of these neurons. The data further support the similarity of R6/2 mice to HD, and are consistent with the occurrence of an excitotoxic process in striatum in both.

Original languageEnglish (US)
Pages (from-to)907-917
Number of pages11
JournalNeurobiology of Disease
Volume20
Issue number3
DOIs
StatePublished - Dec 1 2005

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Calbindin 1
Corpus Striatum
Calbindins
Huntington Disease
Transgenic Mice
Neurons
Quinolinic Acid
Intranuclear Inclusion Bodies
Neurotoxins
N-Methylaspartate
Exons
Messenger RNA
Injections

All Science Journal Classification (ASJC) codes

  • Neurology

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Increased calbindin-D28k immunoreactivity in striatal projection neurons of R6/2 Huntington's disease transgenic mice. / Sun, Z.; Wang, H. B.; Deng, Yunping; Lei, W. L.; Xie, J. P.; Meade, C. A.; Del Mar, N.; Goldowitz, D.; Reiner, Anton.

In: Neurobiology of Disease, Vol. 20, No. 3, 01.12.2005, p. 907-917.

Research output: Contribution to journalArticle

Sun, Z. ; Wang, H. B. ; Deng, Yunping ; Lei, W. L. ; Xie, J. P. ; Meade, C. A. ; Del Mar, N. ; Goldowitz, D. ; Reiner, Anton. / Increased calbindin-D28k immunoreactivity in striatal projection neurons of R6/2 Huntington's disease transgenic mice. In: Neurobiology of Disease. 2005 ; Vol. 20, No. 3. pp. 907-917.
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