The encephalopathy associated with murine acquired immunodeficiency syndrome.
Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an immune deficiency syndrome together with an encephalopathy characterized by impairments in spatial learning and memory. These cognitive deficits are evident before the appearance of neuron loss and lymphoid cell invasion of the brain. Nonetheless, a prominent gliosis and a variety of neurochemical changes precede the development of cognitive deficits. The neurochemical abnormalities include significant decreases in striatal Met-enkephalin and substance P (but not somatostatin), increases in concentrations of quinolinic acid and platelet-activating factor, and alterations in brain fyn kinase. At this stage of the infection, some of these neurochemical changes can be reversed by glutamate receptor antagonists, cytokine inhibitors, and anti-retroviral agents. In later stages of the infection, however, the infected mice develop irreversible neuronal loss, invasion of hematopoietic cells, and increased viral burden in the CNS. In addition, motor-neuron dysfunction (hindlimb paralysis, weakness, and ataxia) and seizures are sometimes observed during the late stages of infection. Thus, the LP-BM5 MuLV-infected mouse is a useful model for studying the chronology of neurodegenerative changes, ranging from reversible neuron dysfunction to irreversible neuron loss, that are associated with retrovirus-induced immunodeficiency.
Sei
Y
Y
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20892, USA. ysei@mx3.usuhs.mil
Kustova
Y
Y
Li
Y
Y
Morse
H C
HC
Skolnick
P
P
Basile
A S
AS
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001927:Brain Diseases / Q000503:physiopathology* / Q000523:psychology / Q000821:virology*; D018782:Maze Learning / Q000502:physiology; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D009498:Neurotoxins / Q000378:metabolism
D009498:Neurotoxins