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

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

doi:10.3233/JAD-151066

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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	677-682
Number of pages	6
Journal	Journal of Alzheimer's Disease
Volume	51
Issue number	3
DOIs	https://doi.org/10.3233/JAD-151066
Publication status	Published - 30 Mar 2016

Keywords

Alzheimer Disease/drug therapy
Amyloid beta-Protein Precursor/genetics
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
Seizures/drug therapy

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title = "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.",

keywords = "Alzheimer Disease/drug therapy, Amyloid beta-Protein Precursor/genetics, 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, Seizures/drug therapy",

author = "Sierksma, \{Annerieke S R\} and \{de Nijs\}, Laurence and Govert Hoogland and Tim Vanmierlo and \{van Leeuwen\}, \{Fred W\} and Rutten, \{Bart P F\} and Steinbusch, \{Harry W M\} and Jos Prickaerts and \{van den Hove\}, \{Daniel L A\}",

year = "2016",

month = mar,

day = "30",

doi = "10.3233/JAD-151066",

language = "English",

volume = "51",

pages = "677--682",

journal = "Journal of Alzheimer's Disease",

issn = "1387-2877",

publisher = "SAGE Publications Ltd",

number = "3",

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TY - JOUR

T1 - Fluoxetine Treatment Induces Seizure Behavior and Premature Death in APPswe/PS1dE9 Mice

AU - Sierksma, Annerieke S R

AU - de Nijs, Laurence

AU - Hoogland, Govert

AU - Vanmierlo, Tim

AU - van Leeuwen, Fred W

AU - Rutten, Bart P F

AU - Steinbusch, Harry W M

AU - Prickaerts, Jos

AU - van den Hove, Daniel L A

PY - 2016/3/30

Y1 - 2016/3/30

N2 - 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.

AB - 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.

KW - Alzheimer Disease/drug therapy

KW - Amyloid beta-Protein Precursor/genetics

KW - Animals

KW - Anticonvulsants/pharmacology

KW - Body Weight/drug effects

KW - Disease Models, Animal

KW - Fluoxetine/pharmacology

KW - Humans

KW - Logistic Models

KW - Male

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Neuroprotective Agents/pharmacology

KW - Presenilin-1/genetics

KW - Seizures/drug therapy

U2 - 10.3233/JAD-151066

DO - 10.3233/JAD-151066

M3 - Article

C2 - 26890781

SN - 1387-2877

VL - 51

SP - 677

EP - 682

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

IS - 3

ER -

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

Abstract

Keywords

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