Abstract
Increasing evidence supports the involvement of amyloid β-peptide (Aβ) and an excitotoxic mechanism of neuronal injury in the pathogenesis of Alzheimer's disease. However, approaches aimed at preventing Aβ toxicity and neurofibrillary degeneration are undeveloped. We now report that anticonvulsants (carbamazepine, phenytoin, and valproic acid) can protect cultured rat hippocampal neurons againsts Aβ- and glutamate-induced injury. Each of the anticonvulsant attentuated the elevated of intracellular free calcium levels [(Ca2+)i] elicited by Aβ or glutamate suggesting that their neuroprotective mechanism of action involved stabilization of [Ca2+]i. These compounds were effective at clinically relevant concentrations (carbamazepine, 100 nM-10 μM; phenytoin, 100 nM-1 μM; valproic acid, 100 nM-100 μM). The anticonvulsants suppressed glutamate-induced alterations in tau and ubiquitin immunoreactivities. Compounds that stabilize [Ca2+]i may afford protection against the kinds of insults believed to underlie neuronal injury in Alzheimer's disease.
Original language | English (US) |
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Pages (from-to) | 187-198 |
Number of pages | 12 |
Journal | Neurobiology of Aging |
Volume | 16 |
Issue number | 2 |
DOIs | |
State | Published - 1995 |
Externally published | Yes |
Keywords
- Alzheimer's disease
- Anticonvulsant
- Calcium
- Carbamazepine
- Fura-2
- Glutamate
- Hippocampus
- Microtubule-associated protein
- Neurofibrillary tangle
- Phenytoin
- Phosphorylation
- Tau
- Valproic acid
ASJC Scopus subject areas
- Aging
- Developmental Biology
- Geriatrics and Gerontology
- Clinical Neurology
- General Neuroscience
- Biological Psychiatry
- Developmental Neuroscience
- Neurology
- General Psychology