Distinct subsets of nucleus basalis neurons exhibit similar sensitivity to excitotoxicity

Neuroreport. 2002 May 7;13(6):767-72. doi: 10.1097/00001756-200205070-00007.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Protein Precursor / biosynthesis*
  • Animals
  • Basal Nucleus of Meynert / drug effects
  • Basal Nucleus of Meynert / metabolism*
  • Basal Nucleus of Meynert / physiopathology
  • Biomarkers / analysis
  • Carbocyanines
  • Cell Count
  • Choline O-Acetyltransferase / metabolism
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / metabolism*
  • Cholinergic Fibers / pathology
  • Down-Regulation / physiology
  • Fluorescent Dyes
  • Immunoglobulin G
  • Immunohistochemistry
  • Male
  • N-Methylaspartate / pharmacology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / pathology
  • Neurotoxins / pharmacology*
  • Nuclear Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Nerve Growth Factor / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • Biomarkers
  • Carbocyanines
  • Fluorescent Dyes
  • Immunoglobulin G
  • Neurotoxins
  • Nuclear Proteins
  • Receptor, Nerve Growth Factor
  • cyanine dye 3
  • N-Methylaspartate
  • Choline O-Acetyltransferase
  • Acetylcholine