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[P6]: The embryonic MGE, LGE and cortex contribute progenitors to the adult SVZ
Author(s) -
Young K.M.,
Kessaris N.,
Fogarty M.,
Haines R.,
Richardson W.D.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.070
Subject(s) - citation , psychology , library science , cognitive science , computer science
Previous studies demonstrated that elevation in the levels of the pro-inflammatory cytokine interleukin-1 (IL-1) within the brain is involved in mediating the memory impairments associated with inflammation and aging. In the present study, we used a model of chronic stress, in which each mouse was isolated in an individual cage for 3 weeks. In both the contextual fear conditioning (FC) test and the spatial version of the Morris water maze (MWM) paradigm, which depend on hippocampal functioning, isolated mice displayed significant memory impairments. Isolation had no effect on the hippocampus independent auditory-cued FC and the non-spatial version of the MWM. Isolation caused a significant elevation in hippocampal IL-1 levels as well as a significant decrease in hippocampal neurogenesis. To explore the role of hippocampal IL-1 in stress-induced memory impairments and suppressed neurogenesis, neural precursor cells (NPCs) were isolated from neonatal mice with transgenic over-expression of IL-1 receptor antagonist (IL-1raTG) under the GFAP promoter, labeled with PKH-26 and transplanted into the hippocampus of WT mice. Three weeks later, transplanted cells, expressing mainly astrocytic markers, could be observed within the hippocampus, and the levels of hippocampal IL-1ra were markedly elevated. In isolated mice, transplantation of IL1raTG NPCs completely rescued the memory impairments and significantly increased hippocampal neurogenesis, compared with isolated mice transplanted with WT cells or sham-operated only. The transplantation had no effect in non-stressed mice. These findings elucidate the role of IL-1 in the pathophysiology of chronic stress and suggest that the intra-hippocampal transplantation of transgenic IL-1raTG NPCs may provide a useful therapeutic procedure for IL-1-mediated memory disturbances in other conditions, particularly neurodegenerative diseases.