Altered brain fyn kinase in a murine acquired immunodeficiency syndrome.
Mice infected with the replication-defective virus (BM5def) in the LP-BM5 murine leukemia virus (MuLV) mixture develop an immune deficiency syndrome and encephalopathy characterized by impaired spatial learning and memory as demonstrated in the Morris water maze. However, the molecular mechanism (or mechanisms) underlying this cognitive deficit remains unknown. Here we report that brain fyn kinase, which has been proposed to be involved in spatial learning and memory, was unresponsive to glutamatergic stimulation in mice with MAIDS. Thus, whereas application of glutamate to hippocampal slices from control mice increased fyn protein tyrosine kinase (PTK) activity more than 2.5-fold, these changes were significantly impaired in LP-BM5 MuLV-infected mice. Moreover, mice with MAIDS exhibited an abnormal histological distribution of fyn PTK in the hippocampus. These findings suggest that virus-associated disruption of fyn kinase-mediated signaling contributes to the cognitive deficits observed in mice with MAIDS and other retrovirus-induced encephalopathies.
Sei
Y
Y
Laboratory of Neuroscience, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Whitesell
L
L
Kustova
Y
Y
Paul
I A
IA
Morse
H C
HC
Skolnick
P
P
Basile
A S
AS
D000818:Animals; D001921:Brain / Q000201:enzymology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000201:enzymology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D014443:Tyrosine / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn