title: Kinin B2 receptor can play a neuroprotective role in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is characterized by cognitive decline, presence of amyloid-beta peptide (Aβ) aggregates and neurofibrillary tangles. Kinins act through B1 and B2 G-protein coupled receptors (B1R and B2R). Chronic infusion of Aβ peptide leads to memory impairment and increases in densities of both kinin receptors in memory processing areas. Similar memory impairment was observed in C57BL/6 mice (WTAβ) but occurred earlier in mice lacking B2R (KOB2Aβ) and was absent in mice lacking B1R (KOB1Aβ). Thus, the aim of this study was to evaluate the participation of B1R and B2R in Aβ peptide induced cognitive deficits through the evaluation of densitiesof kinin receptors, synapses, cell bodies and number of Aβ deposits in brain ofWTAβ, KOB1Aβ and KOB2Aβ mice. An increase in B2R density was observed in both WTAβ and KOB1Aβ in memory processing related areas. KOB1Aβ showed a decrease in neuronal density and an increase in synaptic density and, in addition, an increase in Aβ deposits in KOB2Aβ was observed. In conclusion, memory preservation in KOB1Aβ, could be due to the increase in densities of B2R, suggesting a neuroprotective role for B2R, reinforced by the increased number of Aβ plaques in KOB2Aβ. Our data point to B2R as a potential therapeutic target in AD.
authors.affiliation: Department of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, SP CEP 01221-020, Brazil; Research Group on Neuropharmacology of Aging, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Caetano
authors.affiliation: Department of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, SP CEP 01221-020, Brazil; Research Group on Neuropharmacology of Aging, Brazil.
authors.forename: K E
authors.initials: KE
authors.lastname: Dong-Creste
authors.affiliation: Department of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, SP CEP 01221-020, Brazil.
authors.forename: F A
authors.initials: FA
authors.lastname: Amaral
authors.affiliation: Department of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, SP CEP 01221-020, Brazil.
authors.forename: K C
authors.initials: KC
authors.lastname: Monteiro-Silva
authors.affiliation: Department of Biophysics, Federal University of Sao Paulo, São Paulo, SP CEP 04021-001, Brazil.
authors.forename: J B
authors.initials: JB
authors.lastname: Pesquero
authors.affiliation: Department of Biochemistry, Federal University of Sao Paulo, São Paulo, SP CEP 04021-001, Brazil.
authors.forename: M S
authors.initials: MS
authors.lastname: Araujo
authors.affiliation: Department of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, SP CEP 01221-020, Brazil.
authors.forename: W R
authors.initials: WR
authors.lastname: Montor
authors.affiliation: School of Arts, Sciences and Humanities and Graduation Course on Pharmacology at Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP CEP 03828-080, Brazil; Research Group on Neuropharmacology of Aging, Brazil.
authors.forename: T A
authors.initials: TA
authors.lastname: Viel
authors.affiliation: Department of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, SP CEP 01221-020, Brazil; Research Group on Neuropharmacology of Aging, Brazil.
authors.forename: H S
authors.initials: HS
authors.lastname: Buck
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis / Q000473:pathology; D000818:Animals; D001923:Brain Chemistry; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects; D043782:Receptor, Bradykinin B2 / Q000187:drug effects / Q000235:genetics; D013569:Synapses
chemical_list: D016229:Amyloid beta-Peptides; D043782:Receptor, Bradykinin B2
keywords: Alzheimer's disease; Amyloid beta; B2 receptor; Bradykinin; Knockout mice