title: Memantine protects cholinergic and glutamatergic septal neurons from Aβ1-40-induced toxicity.
abstract: The medial septal region (medial septum and diagonal band of Broca, MS/DB) controls hippocampal excitability and synaptic plasticity. MS/DB cholinergic neurons degenerate early in Alzheimer's disease (AD). The presence of MS/DB glutamatergic neurons that project to the hippocampus and are vulnerable to Aβ suggests that excitotoxicity plays a role in AD septal degeneration and hippocampal dysfunction. To demonstrate the presence of excitotoxicity in Aβ-induced septal damage, we compared rats injected with Aβ1-40 into the MS/DB with animals treated with memantine prior, during and after Aβ1-40 injections. Controls were injected with phosphate buffered saline (PBS). MS/DB cholinergic, glutamatergic and GABAergic neurons were immunochemically identified. The number of MS/DB neurons was estimated using stereology. Our results show that memantine blocks Aβ1-40-induced septal damage and suggest that excitotoxicity plays a role in basal forebrain neurodegeneration.
authors: Center for Biomedical Research, The University of Texas at Brownsville, 80 Fort Brown, Brownsville, TX 78520, USA. Luis.colom@utb.edu
authors: L V
authors: LV
authors: Colom
authors: M T
authors: MT
authors: Castaneda
authors: D
authors: D
authors: Aleman
authors: A
authors: A
authors: Touhami
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002452:Cell Count; D059329:Cholinergic Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D020665:Septum of Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005971:Glutamates; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C078592:amyloid beta-protein (1-40); D008559:Memantine