In vivo regulation of amyloid precursor protein secretion in rat neocortex by cholinergic activity

The European Journal of Neuroscience
S RossnerV Bigl

Abstract

The proteolytic cleavage of the amyloid precursor protein (APP) has been shown to be modulated through specific muscarinic receptor activation in vitro in both transfected cell lines and native brain slices, whereas a demonstration of receptor-mediated control of APP processing under in vivo conditions is still lacking. To simulate alterations in muscarinic receptor stimulation in vivo, we have (i) specifically reduced the cortical cholinergic innervation in rats using partial immunolesions with 192IgG-saporin, and (ii) restored cholinergic function in lesioned rats by transplantation of nerve growth factor producing fibroblasts. While total APP levels in cortical homogenates were unaffected by cholinergic deafferentation, we observed a significant reduction in the abundance of secreted APP and a concomitant increase in membrane-bound APP. These changes were reversed in immunolesioned rats with nerve growth factor-producing fibroblasts. There was a strong positive correlation between the ratio of secreted APP to membrane-bound APP and the activity of choline acetyltransferase and M1 muscarinic acetylcholine receptor density (measured by [3H]pirenzepine binding) in experimental groups. Additionally, we observed a transient decre...Continue Reading

References

Nov 1, 1991·Brain Research·T KawarabayashiS Hirai
Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J D BuxbaumP Greengard
Aug 15, 1995·Proceedings of the National Academy of Sciences of the United States of America·R K LeeR M Nitsch
Aug 30, 1994·Biochemical and Biophysical Research Communications·R HaringY Karton
Sep 1, 1994·Journal of Neuropathology and Experimental Neurology·D J Selkoe
Apr 1, 1994·The Journal of Comparative Neurology·J G BeesonF H Gage
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·W WallaceV Haroutunian
Feb 23, 1996·The Journal of Biological Chemistry·R M NitschR J Wurtman
Jan 15, 1996·Journal of Neuroscience Research·J YuR J Perez-Polo
Feb 1, 1997·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·J ApeltV Bigl

❮ Previous
Next ❯

Citations

Oct 21, 2006·Journal of Neural Transmission·K Maurer, S Hoyer
Sep 28, 1999·Trends in Pharmacological Sciences·M Racchi, S Govoni
May 6, 1998·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·S Rossner
Apr 13, 1999·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·M P Mattson, W A Pedersen
Dec 13, 2003·Neurobiology of Learning and Memory·Alexandra BourChantal Mathis
Feb 4, 1999·Journal of Neurochemistry·J Mills, P B Reiner
Feb 23, 2010·Behavioural Brain Research·Grazyna NiewiadomskaMarcin Mazurkiewicz
Feb 9, 2008·Neurobiology of Aging·Eugenio AztiriaGiampiero Leanza
Mar 12, 2005·Journal of the Neurological Sciences·Barbara BorroniAlessandro Padovani
Jan 21, 2006·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Wolfgang Liskowsky, Reinhard Schliebs
Dec 31, 2005·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Alán AlpárUlrich Gärtner
Apr 27, 2005·Brain Research. Brain Research Reviews·Silvia MandelMoussa B H Youdim
Dec 29, 2000·Japanese Journal of Pharmacology·A Fisher
Dec 5, 2012·Neuropharmacology·Helena JaníčkováVladimír Doležal
Apr 29, 2010·Journal of Pharmacological Sciences·Kung-Shing LeeIkunobu Muramatsu
Apr 28, 2005·Expert Review of Neurotherapeutics·Nicolaas Paul L G Verhoeff
Feb 8, 2007·Reviews in the Neurosciences·Grazyna NiewiadomskaGernot Riedel
Feb 24, 2001·Annals of the New York Academy of Sciences·O Isacson, L Lin
Feb 24, 2001·Annals of the New York Academy of Sciences·A FisherZ Pittel
Jan 10, 2021·Molecular and Cellular Endocrinology·Juliane de Souza CardosoRejane Giacomelli Tavares
Nov 23, 2000·Journal of Medicinal Chemistry·C C FelderN DeLapp
Oct 3, 2002·Molecular and Cellular Neurosciences·Simona CapsoniAntonino Cattaneo
Dec 2, 2004·Journal of Neuroscience Research·Moussa B H YoudimTamar Amit

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Forebrain- Circuits

Basal forebrain is a region in the brain important for production of acetylcholine and is the major cholinergic output of the CNS. Discover the latest research on circuits in the basal forebrain here.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.