title: Longitudinal brain corticotropin releasing factor and somatostatin in a transgenic mouse (TG2576) model of Alzheimer's disease.
abstract: Neuropeptides corticotropin releasing factor (CRF) and somatostatin (SRIF) are substantially decreased in cortical regions of Alzheimer's disease (AD) post-mortem brain tissue. The accumulation of amyloid-beta (Abeta) in AD brain has been postulated to be neurotoxic. Using male Tg2576 mice transgenic over-expressing amyloid-beta protein precursor (APP), we examined brain concentrations of CRF and SRIF at 12, 18 and 24 months. Mice were evaluated for locomotor activity and spatial memory. The APP mice had continued increased locomotor activity from 6 months of age compared to controls. Spatial memory was impaired beginning at 12 months in the APP mice relative to controls. APP mice at 24 months had a significantly higher number of amyloid plaques when compared to the 12 and 18 month time points. Brain concentrations of SRIF and CRF were significantly altered in a number of cortical and sub-cortical brain regions relative to controls, but in most regions were increased rather than decreased as in clinical AD. This data shows that although the insertion of the APP gene does cause age dependent increase in plaque load, it does not cause a change in regional neuropeptides consistent with AD, suggesting that neuropeptide changes in AD are not solely due to Abeta load.
authors.affiliation: Department of Pharmacology and Toxicology, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Horgan
authors.forename: Jose Javier
authors.initials: JJ
authors.lastname: Miguel-Hidalgo
authors.forename: Martha
authors.initials: M
authors.lastname: Thrasher
authors.forename: Garth
authors.initials: G
authors.lastname: Bissette
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008124:Locomotion / Q000502:physiology; D008297:Male; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D013004:Somatostatin / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D013004:Somatostatin; D003346:Corticotropin-Releasing Hormone