Daily rhythms of cognition-related factors are modified in an experimental model of Alzheimer's disease.
The accumulation of amyloid-β (Aβ) peptides in the brain of Alzheimer disease patients is associated to cognitive deficit, increased oxidative stress, and alterations in the circadian rhythms. Brain-derived neurotrophic factor (BDNF) and Neurogranin (RC3), play an important role in the synaptic plasticity underlying memory and learning. Previously, we observed BDNF and RC3 expression follow a daily rhythmic pattern in the hippocampus of young rats. The objective of this study was to investigate the effects of an intracerebroventricular (i.c.v) injection of aggregated Aβ peptide (1-42) on temporal patterns of ApoE protein, Bdnf and Rc3 mRNA, lipid peroxidation (LPO) and reduced glutathione (GSH) levels, in the rat hippocampus. We observed an i.c.v. injection of Aβ aggregates phase shifts daily BDNF and RC3 expression as well as LPO and decreased the mesor of GSH rhythms. ApoE protein levels vary rhythmically throughout the day. ApoE levels increase at ZT 03:39±00:22 in the hippocampus of control rats and at ZT 06:30±00:28 in the treated animals. Thus, elevated levels of Aβ aggregates, characteristic of AD, altered temporal patterns of cognition related-factors, probably, as a consequence of changes in the daily variation of ApoE-mediated Aβ aggregates clearance as well as in the 24h rhythms of the cellular redox state.
Laboratory of Chronobiology, Multidisciplinary Institute of Biological Research-San Luis (IMIBIO-SL), National Council of Science and Technology (CONICET), National University of San Luis (UNSL), Av Ejército de los Andes N° 950, D5700HHW San Luis, Argentina.
Lorena
L
Navigatore-Fonzo
Laboratory of Chronobiology, Multidisciplinary Institute of Biological Research-San Luis (IMIBIO-SL), National Council of Science and Technology (CONICET), National University of San Luis (UNSL), Av Ejército de los Andes N° 950, D5700HHW San Luis, Argentina.
Andrea
A
Castro
Laboratory of Chronobiology, Multidisciplinary Institute of Biological Research-San Luis (IMIBIO-SL), National Council of Science and Technology (CONICET), National University of San Luis (UNSL), Av Ejército de los Andes N° 950, D5700HHW San Luis, Argentina.
Verónica
V
Pignataro
Laboratory of Biology of Reproduction, Multidisciplinary Institute of Biological Research-San Luis (IMIBIO-SL), National Council of Science and Technology (CONICET), National University of San Luis (UNSL), Av Ejército de los Andes N° 950, D5700HHW San Luis, Argentina.
Marisa
M
Garraza
Laboratory of Biology of Reproduction, Multidisciplinary Institute of Biological Research-San Luis (IMIBIO-SL), National Council of Science and Technology (CONICET), National University of San Luis (UNSL), Av Ejército de los Andes N° 950, D5700HHW San Luis, Argentina.
Marilina
M
Casais
Laboratory of Chronobiology, Multidisciplinary Institute of Biological Research-San Luis (IMIBIO-SL), National Council of Science and Technology (CONICET), National University of San Luis (UNSL), Av Ejército de los Andes N° 950, D5700HHW San Luis, Argentina. Electronic address: acanzu@unsl.edu.ar.
Ana Cecilia
AC
Anzulovich
D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051579:Neurogranin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; C496651:Nrgn protein, rat; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D051579:Neurogranin; D008315:Malondialdehyde; D005978:Glutathione
Alzheimer disease; ApoE; BDNF; Daily rhythm; GSH; Lipid peroxidation