Memantine protects cholinergic and glutamatergic septal neurons from Aβ1-40-induced toxicity.

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.