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DOI: 10.1055/s-0033-1353304
Improved neuritogenesis and mitochondrial dynamics by levetiracetam might explain cognitive improvement in brain aging and animal models of Alzheimer's disease
The antiepileptic levetiracetam (Lev) has been shown to improve hippocampal hyperactivity associated with Mild Cognitive Impairment (MCI) in patients and cognitive deficits in an animal model of Alzheimer's disease (AD). These effects have been explained by improvement of synaptic function but the mechanism has not yet been clarified, also effects on mitochondrial function seem to be involved. Since loss of synapses and neurites associated with impaired mitochondrial function and dynamics (fission and fusion) are typical for brain aging and early AD, we assessed the effects of Lev on neurite outgrowth and mitochondrial parameters. Human neuroblastoma cells (SY5Y) and PC12 cells were used under conditions imitating aging and SY5Y cells expressing slightly higher beta-amyloid levels typical for very early stages of AD. These cells exhibit impaired neuritogenesis and mitochondrial dynamics already under baseline conditions and/or after treatment with rotenone. Lev improves neuritogenesis and mitochondrial dynamics in both cell lines following oxidative stress and rotenone treatment (complex I inhibition) at similar concentrations and also had some beneficial effects on both parameters in SY5Y cells overexpressing beta-amyloid. Improved neuroplasticity might be associated by the beneficial effects of Lev on cognitive functions independent of its anticonvulsant properties. This study was supported by UCB.