Distinct subsets of nucleus basalis neurons exhibit similar sensitivity to excitotoxicity.
Excitotoxic lesions in the magnocellular nucleus basalis (MBN) lead to a significant damage of cholinergic neurons concomitant with increased amyloid precursor protein (APP) expression in the cerebral cortex. However, the sensitivity of non-cholinergic neurons to excitotoxicity, and changes of APP expression in the damaged MBN are still elusive. Hence, we performed multiple-labeling immunocytochemistry for choline-acetyltransferase (ChAT), neuron-specific nuclear protein (NeuN) and APP 4, 24, and 48 h after NMDA infusion in the MBN. Whereas all cholinergic neurons were immunoreactive for NeuN, this neuronal marker also labeled a population of ChAT-immunonegative non-cholinergic neurons. Both neuron populations exhibited a similar degree of sensitivity to NMDA excitotoxicity that became evident as early as 4 h post-lesion. Cholinergic MBN neurons showed abundant APP immunoreactivity (approximately 90%), while only a fraction (approximately 20-30%) of non-cholinergic neurons expressed the protein. Remarkably, cholinergic but not non-cholinergic neurons retained their APP immunoreactivity after NMDA infusion. In conclusion, cholinergic MBN neurons are not preferentially sensitive to short-term excitotoxicity, but are one of the major sources of APP in the basal forebrain.
Harkany
Tibor
T
Department of Molecular Neurobiology, University of Groningen, The Netherlands.
Varga
Csaba
C
Grosche
Jens
J
Mulder
Jan
J
Luiten
Paul G M
PG
Hortobágyi
Tibor
T
Penke
Botond
B
Härtig
Wolfgang
W
D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D002232:Carbocyanines; D002452:Cell Count; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000502:physiology; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D007150:Immunohistochemistry; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D002232:Carbocyanines; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D009498:Neurotoxins; D009687:Nuclear Proteins; D020800:Receptor, Nerve Growth Factor; C089187:cyanine dye 3; D016202:N-Methylaspartate; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine