title: Systemic administration of substance P recovers beta amyloid-induced cognitive deficits in rat: involvement of Kv potassium channels.
abstract: 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-β (Aβ)-induced up-regulation of voltage-gated potassium channel subunits could be considered a significant step in Aβ brain toxicity. The aim of this study was to evaluate whether SP could reduce, in vivo, Aβ-induced overexpression of Kv subunits. Rats were intracerebroventricularly infused with amyloid-β 25-35 (Aβ25-35, 20 µg) peptide. SP (50 µg/Kg, i.p.) was daily administered, for 7 days starting from the day of the surgery. Here we demonstrate that the Aβ infused rats showed impairment in cognitive performances in the Morris water maze task 4 weeks after Aβ25-35 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 Aβ, 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.
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ratano
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ciotti
authors.forename: Fulvio
authors.initials: F
authors.lastname: Florenzano
authors.forename: Stefania Lucia
authors.initials: SL
authors.lastname: Nori
authors.forename: Roberta
authors.initials: R
authors.lastname: Marolda
authors.forename: Maura
authors.initials: M
authors.lastname: Palmery
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Rinaldi
authors.forename: Cristina
authors.initials: C
authors.lastname: Zona
authors.forename: Roberta
authors.initials: R
authors.lastname: Possenti
authors.forename: Pietro
authors.initials: P
authors.lastname: Calissano
authors.forename: Cinzia
authors.initials: C
authors.lastname: Severini
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051665:Kv1.4 Potassium Channel / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D051665:Kv1.4 Potassium Channel; D010446:Peptide Fragments; D024642:Potassium Channels, Voltage-Gated; C074636:amyloid beta-protein (25-35); D013373:Substance P