title: Increase in Alzheimer's related markers preceeds memory disturbances: studies in vasopressin-deficient Brattleboro rat.
abstract: Alzheimer's disease (AD) is the most common form of dementia in the elderly. For more effective therapy early diagnostic markers could be beneficial. Therefore we compared one year old rats with adults and examined if changes in possible brain markers of AD preceeded memory decline. We also tested if vasopressin-deficient animals were useful model of AD as vasopressin has well known positive effect on memory and AD patient has decreased vasopressin production. We compared adult (3 month) and old (12 month), normal and vasopressin-deficient Brattleboro rats. To receive a comprehensive picture about their memory we examined their social discrimination, object discrimination and conditioned learning abilities (shuttle box). Amyloid precursor protein (APP), mitogen-activated protein kinase 1 (MAPK1), β-actin and tryptophan 2,3-dioxygenase 2 (TDO2) mRNA levels was measured by quantitative PCR. There was no difference between the memory of adult and aged groups. The vasopressin-deficient rats at both ages showed a weaker performance in the course of social and object discrimination tests and a higher escape failure during the shuttle box experiment. The brain marker mRNAs of the elder animals were higher than the levels of the adults, but the absence of vasopressin had no influence on them. Thus, the one year old rats showed elevated levels of AD-related markers, but memory deficits were observable only in vasopressin deficient animals. Vasopressin does not seem to have pathogenic role in AD. Changes in the studied markers might predict later symptoms, although further studies are required for confirmation.
authors.affiliation: Department of Behavioural Neurobiology, Institute of Experimental Medicine, Budapest Szigony 43, 1083 Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Varga
authors.affiliation: Department of Behavioural Neurobiology, Institute of Experimental Medicine, Budapest Szigony 43, 1083 Budapest, Hungary.
authors.forename: Barbara
authors.initials: B
authors.lastname: Klausz
authors.affiliation: Department of Behavioural Neurobiology, Institute of Experimental Medicine, Budapest Szigony 43, 1083 Budapest, Hungary; Department of Psychiatry, Alzheimer Research Group, University of Szeged, Szeged, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Domokos
authors.affiliation: Department of Psychiatry, Alzheimer Research Group, University of Szeged, Szeged, Hungary.
authors.forename: Sára
authors.initials: S
authors.lastname: Kálmán
authors.affiliation: Department of Psychiatry, Alzheimer Research Group, University of Szeged, Szeged, Hungary.
authors.forename: Magdolna
authors.initials: M
authors.lastname: Pákáski
authors.affiliation: Department of Psychiatry, Alzheimer Research Group, University of Szeged, Szeged, Hungary.
authors.forename: Szabina
authors.initials: S
authors.lastname: Szűcs
authors.affiliation: Department of Psychiatry, Alzheimer Research Group, University of Szeged, Szeged, Hungary.
authors.forename: Dénes
authors.initials: D
authors.lastname: Garab
authors.affiliation: Laboratory of Functional Genomics, Biological Research Centre, Szeged, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Zvara
authors.affiliation: Laboratory of Functional Genomics, Biological Research Centre, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Puskás
authors.affiliation: Department of Psychiatry, Alzheimer Research Group, University of Szeged, Szeged, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Kálmán
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
authors.forename: Júlia
authors.initials: J
authors.lastname: Tímár
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Bagdy
authors.affiliation: Department of Behavioural Neurobiology, Institute of Experimental Medicine, Budapest Szigony 43, 1083 Budapest, Hungary. Electronic address: zelena.dora@koki.mta.hu.
authors.forename: Dóra
authors.initials: D
authors.lastname: Zelena
mesh_terms: D000199:Actins / Q000032:analysis; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000032:analysis*; D020790:Diabetes Insipidus, Neurogenic; D004195:Disease Models, Animal; D042241:Early Diagnosis; D008297:Male; D008569:Memory Disorders / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011910:Rats, Brattleboro; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014366:Tryptophan Oxygenase / Q000032:analysis / Q000378:metabolism
chemical_list: D000199:Actins; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D012333:RNA, Messenger; D014366:Tryptophan Oxygenase; D019950:Mitogen-Activated Protein Kinase 1
keywords: APP; MAPK1; Object and social discrimination; Shuttle box; TDO2; β-Actin