TY - JOUR
T1 - Presenilin-1 familial Alzheimer's disease mutation alters hippocampal neurogenesis and memory function in CCL2 null mice
AU - Kiyota, Tomomi
AU - Morrison, Christine M.
AU - Tu, Guihua
AU - Dyavarshetty, Bhagyalaxmi
AU - Weir, Robert A.
AU - Zhang, Gang
AU - Xiong, Huangui
AU - Gendelman, Howard E.
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Aberrations in hippocampal neurogenesis are associated with learning and memory, synaptic plasticity and neurodegeneration in Alzheimer's disease (AD). However, the linkage between them, β-amyloidosis and neuroinflammation is not well understood. To this end, we generated a mouse overexpressing familial AD (FAD) mutant human presenilin-1 (PS1) crossed with a knockout (KO) of the CC-chemokine ligand 2 (CCL2) gene. The PS1/CCL2KO mice developed robust age-dependent deficits in hippocampal neurogenesis associated with impairments in learning and memory, synaptic plasticity and long-term potentiation. Neurogliogenesis gene profiling supported β-amyloid independent pathways for FAD-associated deficits in hippocampal neurogenesis. We conclude that these PS1/CCL2KO mice are suitable for studies linking host genetics, immunity and hippocampal function.
AB - Aberrations in hippocampal neurogenesis are associated with learning and memory, synaptic plasticity and neurodegeneration in Alzheimer's disease (AD). However, the linkage between them, β-amyloidosis and neuroinflammation is not well understood. To this end, we generated a mouse overexpressing familial AD (FAD) mutant human presenilin-1 (PS1) crossed with a knockout (KO) of the CC-chemokine ligand 2 (CCL2) gene. The PS1/CCL2KO mice developed robust age-dependent deficits in hippocampal neurogenesis associated with impairments in learning and memory, synaptic plasticity and long-term potentiation. Neurogliogenesis gene profiling supported β-amyloid independent pathways for FAD-associated deficits in hippocampal neurogenesis. We conclude that these PS1/CCL2KO mice are suitable for studies linking host genetics, immunity and hippocampal function.
KW - Chemokine
KW - Hippocampus
KW - Long-term potentiation
KW - Morris water maze
KW - Neurogliogenesis
UR - http://www.scopus.com/inward/record.url?scp=84940573722&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940573722&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2015.06.014
DO - 10.1016/j.bbi.2015.06.014
M3 - Article
C2 - 26112421
AN - SCOPUS:84940573722
SN - 0889-1591
VL - 49
SP - 311
EP - 321
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -