Fluoxetine Treatment Induces Seizure Behavior and Premature Death in APPswe/PS1dE9 Mice.

Abstract

Treatment of Alzheimer's disease (AD) patients with the antidepressant fluoxetine is known to improve memory and cognitive function. However, the mechanisms underlying these effects are largely unknown. To unravel these mechanisms, we aimed to treat APPswe/PS1dE9 mice with fluoxetine. Unexpectedly, with time, an increased number of animals displayed seizure behavior and died. Although spontaneous behavioral seizures have been reported previously in this mouse model, the observation of seizures and death consequential to fluoxetine treatment is new. Our results warrant further research on the underlying mechanisms as this may refine the treatment of AD patients.

• Authors: Annerieke S R Sierksma, Laurence de Nijs, Govert Hoogland, Tim Vanmierlo, Fred W van Leeuwen, Bart P F Rutten, Harry W M Steinbusch, Jos Prickaerts, Daniel L A van den Hove
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 51 Issue 3 Pg. 677-82 ( 2016) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 26890781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• APP protein, human
• Amyloid beta-Protein Precursor
• Anticonvulsants
• Neuroprotective Agents
• PSEN1 protein, human
• Presenilin-1
• Fluoxetine

Topics

• Alzheimer Disease (drug therapy, physiopathology)
• Amyloid beta-Protein Precursor (genetics, metabolism)
• Animals
• Anticonvulsants (pharmacology)
• Body Weight (drug effects)
• Disease Models, Animal
• Fluoxetine (pharmacology)
• Humans
• Logistic Models
• Male
• Mice, Inbred C57BL
• Mice, Transgenic
• Neuroprotective Agents (pharmacology)
• Presenilin-1 (genetics, metabolism)
• Seizures (drug therapy, physiopathology)