| First Author | Spalloni A | Year | 2006 |
| Journal | Exp Neurol | Volume | 197 |
| Issue | 2 | Pages | 505-14 |
| PubMed ID | 16309674 | Mgi Jnum | J:104511 |
| Mgi Id | MGI:3612211 | Doi | 10.1016/j.expneurol.2005.10.014 |
| Citation | Spalloni A, et al. (2006) Molecular and synaptic changes in the hippocampus underlying superior spatial abilities in pre-symptomatic G93A+/+ mice overexpressing the human Cu/Zn superoxide dismutase (Gly(93) --> ALA) mutation. Exp Neurol 197(2):505-14 |
| abstractText | 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 (GLY(93) --> 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. |
