Systemic Administration of Substance P Recovers Beta Amyloid-Induced Cognitive Deficits in Rat: Involvement of Kv Potassium Channels

被引:30
作者
Campolongo, Patrizia [1 ]
Ratano, Patrizia [1 ]
Ciotti, Maria Teresa [2 ]
Florenzano, Fulvio [2 ,3 ]
Nori, Stefania Lucia [4 ]
Marolda, Roberta [2 ]
Palmery, Maura [1 ]
Rinaldi, Anna Maria [5 ]
Zona, Cristina [5 ,6 ]
Possenti, Roberta [5 ]
Calissano, Pietro [3 ]
Severini, Cinzia [2 ]
机构
[1] Sapienza Univ Rome, Dept Physiol & Pharmacol, Rome, Italy
[2] CNR, Inst Cell Biol & Neurobiol, Rome, Italy
[3] European Brain Res Inst, Rome, Italy
[4] Univ Salerno Med Campus, Dept Med & Surg, Baronissi, SA, Italy
[5] Univ Roma Tor Vergata, Dept Neurosci, Rome, Italy
[6] IRCCS Fdn Santa Lucia, Rome, Italy
来源
PLOS ONE | 2013年 / 8卷 / 11期
关键词
EPISODIC-LIKE MEMORY; ALZHEIMERS-DISEASE; CEREBELLAR GRANULE; IN-VIVO; NEURAL MECHANISMS; MAZE PERFORMANCE; MESSENGER-RNA; WATER MAZE; PEPTIDE; PRECURSOR;
D O I
10.1371/journal.pone.0078036
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-beta (A beta)-induced up-regulation of voltage-gated potassium channel subunits could be considered a significant step in A beta brain toxicity. The aim of this study was to evaluate whether SP could reduce, in vivo, A beta-induced overexpression of Kv subunits. Rats were intracerebroventricularly infused with amyloid-beta 25-35 (A beta(25-35), 20 mu g) peptide. SP (50 mu g/Kg, i.p.) was daily administered, for 7 days starting from the day of the surgery. Here we demonstrate that the A beta infused rats showed impairment in cognitive performances in the Morris water maze task 4 weeks after A beta(25-35) 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 A beta, 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.
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页数:11
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