TY - JOUR
T1 - Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system
AU - Chen, Jing
AU - Buchanan, Jessica B.
AU - Sparkman, Nathan L.
AU - Godbout, Jonathan P.
AU - Freund, Gregory G.
AU - Johnson, Rodney W.
N1 - Funding Information:
We thank Dr. James Zachary for assisting with LCM and Dr. Masaaki Nakai (University of Illinois) for helping with IHC staining. Dr. Colm Cunningham at University of Southampton (U.K.) also provided helpful advice on IHC staining. This research was supported by NIH grants AG16710 (R.W.J.), AG023580 (R.W.J.), MH069148 (R.W.J.) and DK64862 (G.G.F.). J.B.B. and J.P.G. were supported by a Ruth L. Kirchstein NRSA Postdoctoral Fellowship.
PY - 2008/3
Y1 - 2008/3
N2 - Acute cognitive disorders are common in elderly patients with peripheral infections but it is not clear why. Here, we injected old and young mice with Escherichia coli lipopolysaccharide (LPS) to mimic an acute peripheral infection and separated the hippocampal neuronal cell layers from the surrounding hippocampal tissue by laser capture microdissection and measured mRNA for several inflammatory cytokines (IL-1β, IL-6, and TNFα) that are known to disrupt cognition. The results showed that old mice had an increased inflammatory response in the hippocampus after LPS compared to younger cohorts. Immunohistochemistry further showed more microglial cells in the hippocampus of old mice compared to young adults, and that more IL-1β-positive cells were present in the dentate gyrus and in the CA1, CA2, and CA3 regions of LPS-treated old mice compared to young adults. In a test of cognition that required animals to effectively integrate new information with a preexisting schema to complete a spatial task, we found that hippocampal processing is more easily disrupted in old animals than in younger ones when the peripheral innate immune system is stimulated. Collectively, the results suggest that aging can facilitate neurobehavioral complications associated with peripheral infections probably by allowing the over expression of inflammatory cytokines in brain areas that mediate cognitive processing.
AB - Acute cognitive disorders are common in elderly patients with peripheral infections but it is not clear why. Here, we injected old and young mice with Escherichia coli lipopolysaccharide (LPS) to mimic an acute peripheral infection and separated the hippocampal neuronal cell layers from the surrounding hippocampal tissue by laser capture microdissection and measured mRNA for several inflammatory cytokines (IL-1β, IL-6, and TNFα) that are known to disrupt cognition. The results showed that old mice had an increased inflammatory response in the hippocampus after LPS compared to younger cohorts. Immunohistochemistry further showed more microglial cells in the hippocampus of old mice compared to young adults, and that more IL-1β-positive cells were present in the dentate gyrus and in the CA1, CA2, and CA3 regions of LPS-treated old mice compared to young adults. In a test of cognition that required animals to effectively integrate new information with a preexisting schema to complete a spatial task, we found that hippocampal processing is more easily disrupted in old animals than in younger ones when the peripheral innate immune system is stimulated. Collectively, the results suggest that aging can facilitate neurobehavioral complications associated with peripheral infections probably by allowing the over expression of inflammatory cytokines in brain areas that mediate cognitive processing.
KW - Aging
KW - Hippocampus
KW - Interleukin-1
KW - Laser capture microdissection
KW - Lipopolysaccharide
KW - Working memory
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U2 - 10.1016/j.bbi.2007.08.014
DO - 10.1016/j.bbi.2007.08.014
M3 - Article
C2 - 17951027
AN - SCOPUS:38649119160
SN - 0889-1591
VL - 22
SP - 301
EP - 311
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
IS - 3
ER -