Molecular and synaptic changes in the hippocampus underlying superior spatial abilities in pre-symptomatic G93A+/+ mice overexpressing the human Cu/Zn superoxide dismutase (Gly93 !
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- 作者：Alida Spalloni ; Raffaella Geracitano ; Nicola Berretta ; Carmelo Sgobio ; Giorgio Bernardi ; Nicola B. Mercuri ; Patrizia Longone and Martine Ammassari-Teule
- 关键词：ALS ; G93A+/+ mice ; Cu/Zn superoxide dismutase (SOD1) gene ; Spatial novelty ; Hippocampus ; Glutamate ; AMPAR GluR1 subunit ; Long-term potentiation
- 刊名：Experimental Neurology
- 出版年：2006
- 出版时间：February 2006
- 年：2006
- 卷：197
- 期：2
- 页码：505-514
- 全文大小：438 K
文摘
Although amyotrophic lateral sclerosis (ALS) is mainly considered as a motor disease, extramotor neural and cognitive alterations have also been reported in ALS patients. There is evidence that mutations in the Cu/Zn superoxide dismutase (SOD1) gene are implicated in about 20 % of familiar ALS and transgenic mice overexpressing the human Cu/Zn superoxide dismutase (GLY93 → ALA) mutation show an ALS-like phenotype. However, while motor behavior has been extensively analyzed in these mutants, little is known on their cognitive abilities. To characterize the pre-symptomatic cognitive profile of G93A+/+ mice, we estimated their capability to detect spatial novelty and examined several indexes of their hippocampal function. We found an enhancement of spatial abilities in mutant mice associated with (1) a higher expression of hippocampal AMPA subunit GluR1 mRNA and of GluR1 protein levels, and (2) an increased induction and maintenance of long-term potentiation (LTP) at Schaffer collateral-CA1 synapses. Thus, before leading to extensive neuronal excitotoxicity, the high endogenous levels of glutamate present in the brain of pre-symptomatic G93A+/+ mice could mediate site-specific molecular and synaptic changes providing favorable conditions to spatial information processing. These findings suggest that identification of pre-symptomatic behavioral changes in murine models of ALS may point to early neural abnormalities selectively associated with mutations in the Cu/Zn superoxide dismutase (SOD1) gene.