Longitudinal brain corticotropin releasing factor and somatostatin in a transgenic mouse (TG2576) model of Alzheimer's disease.
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.
Horgan
Jennifer
J
Department of Pharmacology and Toxicology, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
Miguel-Hidalgo
Jose Javier
JJ
Thrasher
Martha
M
Bissette
Garth
G
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*
D016564:Amyloid beta-Protein Precursor; D013004:Somatostatin; D003346:Corticotropin-Releasing Hormone