Age-dependent spatial memory loss can be partially restored by immune activation.
Aging is often associated with a decline in hippocampus-dependent spatial memory. Here, we show that functional cell-mediated immunity is required for the maintenance of hippocampus-dependent spatial memory. Sudden imposition of immune compromise in young mice caused spatial memory impairment, whereas immune reconstitution reversed memory deficit in immune-deficient mice. Analysis of hippocampal gene expression suggested that immune-dependent spatial memory performance was associated with the expression of insulin-like growth factor (Igf1) and of genes encoding proteins related to presynaptic activity (Syt10, Cplx2). We further showed that memory loss in aged mice could be attributed to age-related attenuation of the immune response and could be reversed by immune system activation. Homeostatic-driven proliferation of lymphocytes, which expands the existing T cell repertoire, restored spatial memory deficits in aged mice. Thus, our results identify a novel function of the immune system in the maintenance of spatial memory and suggest an original approach for arresting or reversing age-associated memory loss.
Ron-Harel
N
N
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Segev
Y
Y
Lewitus
G M
GM
Cardon
M
M
Ziv
Y
Y
Netanely
D
D
Jacob-Hirsch
J
J
Amariglio
N
N
Rechavi
G
G
Domany
E
E
Schwartz
M
M
D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000523:psychology*; D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D017628:Microglia / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000235:genetics; D050857:Synaptotagmins / Q000235:genetics
D017931:DNA Primers; D009419:Nerve Tissue Proteins; D050857:Synaptotagmins; D007334:Insulin-Like Growth Factor I