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Limited effect of serotonergic denervation on beta-amyloid and cognitive impairment in APPswe/PS1dE9 mice.

Ortiz-Barajas O, Ramos-Rodriguez J, Berrocoso E, Garcia Alloza M (2012) Limited effect of serotonergic denervation on beta-amyloid and cognitive impairment in APPswe/PS1dE9 mice. Neuroscience 2012 Abstracts 751.12. Society for Neuroscience, New Orleans, LA.

Summary: Alzheimer’s Disease (AD) is a neurodegenerative disease characterized by progressive cognitive and memory impairment. Amyloid-beta (Aβ) deposition, as senile plaques (SP), seems to play a key role in the development and progression of the illness. Moreover SP tend to accumulate in cortex and hippocampus, relevant areas in learning and memory. On the other hand neuronal loss is the pathological feature that best correlates with duration and severity of the illness and at present animal available animal models hardly reproduce the complexity of the disease. We have previously seen that selective cortical and hipocampal cholinergic denervation, using murine p-75 saporin, may worsen cognitive abilities in APPswe/PS1dE9 mice as well as increase SP deposition in denervated areas. In the present work we lesioned 7 months old APPswe/PS1dE9 mice with 1 µl of 5,7-dyhidroxytiptamine (0.16 µg/µl) injected in the raphe nucleus (RN). In order to guarantee selective removal of cortical and hipocampal serotonergic inervation, and protect noardernergic and dopaminergic neurons, animals were i.p. injected with desipramine and nomifensine before surgery. We observed a clear reduction of tryptophan hydroxilase staining in the RN. In the Morris water maze test we observed learning and memory impairment in APPswe/Ps1dE9 mice, without a synergistic effect of the serotonergic lesion. When we assessed SP deposition we did not observe a significant increase of SP in cortex or hipocampus 14 days after the lesion, as we observed after selective cholinergic denervation. Altogether our data suggest that cognitive impairment and induced SP depositioin observed after cholinergic denervation is not achieved when serotonergic system is affected, supporting a selective effect mediated by different neurotransmitter systems. Acknowledgements: MG-A: RYC-2008-02333, ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (PS09/00969), Fundación Dr. Eugenio Rodriguez Pascual, Junta Andalucia Excelencia (CTS-7847).

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