Amyloid-beta accumulation, neurogenesis, behavior, and the age of rats.
The goals of this research were to describe age-related changes in brain biochemistry and behavior, and the relationships between them. The chronological ages of greatest change are particularly important for targeting interventions. In this experiment, 36 Fischer 344/Brown-Norway rats (3, 12, 20, and 30 months old) were trained in lever boxes on temporal discrimination tasks. The greatest response rate decrease and response pattern change occurred between 12 and 20 months. The biochemical results showed that amyloid-beta peptides (Aβ40 and Aβ42) increased with age. The endothelial expression of the Aβ influx transporter (RAGE) also increased, and the expression of Aβ efflux transporter (LPR-1) decreased, with age. The greatest change in the biochemical measures also were between 12 and 20 months. Twenty additional rats were analyzed for stem cell proliferation, and neurogenesis decreased with age, particularly between about 12 and 20 months. These early changes in brain, biochemistry, and behavior provide opportunity for new therapies or prophylaxis.
Cognitive, Linguistic, and Psychological Sciences.
Russell M
RM
Church
Department of Neurosurgery.
Miles C
MC
Miller
Cognitive, Linguistic, and Psychological Sciences.
David
D
Freestone
Department of Neurosurgery.
Catharine
C
Chiu
Department of Neurosurgery.
Doreen P
DP
Osgood
Biostatistics Core.
Jason T
JT
Machan
Department of Neurosurgery.
Arthur A
AA
Messier
Department of Neurosurgery.
Conrad E
CE
Johanson
Department of Neurosurgery.
Gerald D
GD
Silverberg
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D003216:Conditioning, Operant; D004192:Discrimination, Psychological / Q000502:physiology; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology*; D055495:Neurogenesis; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D016229:Amyloid beta-Peptides; D026901:Membrane Transport Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)