P Campolongo, P Ratano, MT Ciotti, F Florenzano, SL Nori, R Marolda, M Palmery, AMÂ Rinaldi, C Zona, R Possenti, P Calissano, C Severini, PLos One, 2013, 8(11), e78036.
Reduced levels of Substance P (SP), an endogenous neuropeptide endowed with neuroprotective and anti-apoptotic properties, have been found in brain and spinal fluid of Alzheimer’s disease (AD) patients. Potassium (K+) channel dysfunction is implicated in AD development and the amyloid-Î² (AÎ²)-induced up-regulation of voltage-gated potassium channel subunits could be considered a significant step in AÎ² brain toxicity. The aim of this study was to evaluate whether SP could reduce, in vivo, AÎ²-induced overexpression of Kv subunits. Rats were intracerebroventricularly infused with amyloid-Î² 25â€“35 (AÎ²25â€“35, 20 Âµg) peptide. SP (50 Âµg/Kg, i.p.) was daily administered, for 7 days starting from the day of the surgery. Here we demonstrate that the AÎ² infused rats showed impairment in cognitive performances in the Morris water maze task 4 weeks after AÎ²25â€“35 infusion and that this impairing effect was prevented by SP administration.
Kv1.4, Kv2.1 and Kv4.2 subunit levels were quantified in hippocampus and in cerebral cortex by Western blot analysis and immunofluorescence. Interestingly, SP reduced Kv1.4 levels overexpressed by AÎ², both in hippocampus and cerebral cortex.
Our findings provide in vivo evidence for a neuroprotective activity of systemic administration of SP in a rat model of AD and suggest a possible mechanism underlying this effect.