Depletion of rabphilin 3A in a transgenic mouse model (R6/1) of Huntington's disease, a possible culprit in synaptic dysfunction

Ruben Smith; Asa Petersén; Gillian P Bates; Patrik Brundin; Jia-Yi Li

doi:10.1016/j.nbd.2005.05.008

Depletion of rabphilin 3A in a transgenic mouse model (R6/1) of Huntington's disease, a possible culprit in synaptic dysfunction

Neurobiol Dis. 2005 Dec;20(3):673-84. doi: 10.1016/j.nbd.2005.05.008. Epub 2005 Jun 20.

Authors

Ruben Smith¹, Asa Petersén, Gillian P Bates, Patrik Brundin, Jia-Yi Li

Affiliation

¹ Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A10, 221 84 Lund, Sweden.

PMID: 15967669
DOI: 10.1016/j.nbd.2005.05.008

Abstract

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by progressive psychiatric, cognitive, and motor disturbances. We studied the expression of synaptic vesicle proteins in the R6/1 transgenic mouse model of HD. We observed that the levels of rabphilin 3A, a protein involved in exocytosis, is substantially decreased in synapses of most brain regions in R6/1 mice. The appearance of the reduction coincides with the onset of motor deficits and behavioral disturbances. Double immunohistochemistry did not show colocalization between rabphilin 3A and huntingtin aggregates in the HD mice. Using in situ hybridization, we demonstrated that rabphilin 3A mRNA expression was substantially reduced in the R6/1 mouse cortex compared to wild-type mice. Our results indicate that a decrease in mRNA levels underlie the depletion of protein levels of rabphilin 3A, and we suggest that this reduction may be involved in causing impaired synaptic transmission in R6/1 mice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Adaptor Proteins, Signal Transducing / metabolism
Animals
Behavior, Animal / physiology
Brain / metabolism*
Brain / physiopathology
Disease Models, Animal
Down-Regulation / genetics*
Exocytosis / genetics
Huntingtin Protein
Huntington Disease / genetics*
Huntington Disease / metabolism
Huntington Disease / physiopathology
Inclusion Bodies / genetics
Inclusion Bodies / metabolism
Male
Mice
Mice, Transgenic
Movement Disorders / genetics
Movement Disorders / metabolism
Movement Disorders / physiopathology
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / metabolism
Nuclear Proteins / metabolism
Presynaptic Terminals / metabolism*
Presynaptic Terminals / pathology
RNA, Messenger / metabolism
Rabphilin-3A
Synaptic Transmission / genetics*
Synaptic Vesicles / genetics
Synaptic Vesicles / metabolism
Vesicular Transport Proteins / genetics*
Vesicular Transport Proteins / metabolism

Substances

Adaptor Proteins, Signal Transducing
HTT protein, human
Huntingtin Protein
Nerve Tissue Proteins
Nuclear Proteins
RNA, Messenger
Vesicular Transport Proteins