Selective immunolesion of cholinergic neurons leads to long-term changes in 5-HT2A receptor levels in hippocampus and frontal cortex.
Although loss of cholinergic neurons in the basal forebrain is considered a key initial feature in Alzheimer's disease (AD), changes in other transmitter systems, including serotonin and 5-HT(2A) receptors, are also associated with early AD. The aim of this study was to investigate whether elimination of the cholinergic neurons in the basal forebrain directly affects 5-HT(2A) receptor levels. For this purpose intraventricular injection of the selective immunotoxin 192 IgG-Saporin was given to rats in doses of either 2.5 or 5 microg. The rats were sacrificed after 1, 2, 4 and 20 weeks. 5-HT(2A) protein levels were determined by western techniques in frontal cortex and hippocampus. A significant 70% downregulation in frontal cortex and a 100% upregulation in hippocampus of 5-HT(2A) receptor levels were observed 20 weeks after the cholinergic lesion when using the highest dose of 192 IgG-Saporin. Our results show that cholinergic deafferentation leads to decreased frontal cortex and increased hippocampal 5-HT(2A) receptor levels. This is probably a consequence of the interaction between the serotonergic and the cholinergic system that may vary depending on the brain region.
Severino
Maurizio
M
Neurobiology Research Unit, CIMBI, Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital, Copenhagen, Denmark.
Pedersen
Anja F
AF
Trajkovska
Viktorija
V
Christensen
Ellen
E
Lohals
Rasmus
R
Veng
Lone M
LM
Knudsen
Gitte M
GM
Aznar
Susana
S
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013997:Time Factors
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D044402:Receptor, Serotonin, 5-HT2A; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D000109:Acetylcholine