El autismo como una patología sináptica : estudio de la conectividad mediada por NCAM y de su modulación farmacológica
Newly considered as a synaptopathy, autism spectrum disorders (ASD) lacks an effective pharmacological treatment. The aim of this work was to identify a novel molecular target and design a new pharmacological treatment based on synaptic connectivity modulation by using the animal model of autism ind...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2015
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_5750 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_5750.dir/5750.PDF |
| Aporte de: |
| Sumario: | Newly considered as a synaptopathy, autism spectrum disorders (ASD) lacks an effective pharmacological treatment. The aim of this work was to identify a novel molecular target and design a new pharmacological treatment based on synaptic connectivity modulation by using the animal model of autism induced by rat prenatal exposure to Valproic Acid (VPA). At postnatal day (PND) 35, when social and exploratory deficits have already been established, we found in the medial prefrontal cortex (mPFC) and the hippocampus of VPA animals an imbalance in the expression of the neural cell adhesion molecule (NCAM) and its polysialylated variant (PSA-NCAM). Since Fluoxetine (F) has been shown to induce synaptic remodeling, its effects on VPA adhesive imbalance and behavioral features were tested. Early F treatment (10 mg/kg; PND 16-30) fully corrected the exploratory deficit and partially remedied VPA social deficit. Concomitantly to the behavioral benefit, F balanced NCAM/PSA-NCAM levels in the mPFC. Neither a late onset (10 mg/kg; PND 23-37) nor a lower F dose (5 mg/kg; PND 16-30) resulted in additional behavioral benefit. These findings could lead the way in designing new rational drug therapies for ASD. |
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