Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APP(swe)/PS1(dE9) transgenic mice: Effect of long-term treatment with paroxetine

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Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APP(swe)/PS1(dE9) transgenic mice : Effect of long-term treatment with paroxetine. / Olesen, Louise Orum; Sivasaravanaparan, Mithula; Severino, Maurizio et al.

I: Neurobiology of Disease, Bind 104, 08.2017, s. 50-60.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{fc3b80fb8d874dcbaca61055526ec616,
title = "Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APP(swe)/PS1(dE9) transgenic mice: Effect of long-term treatment with paroxetine",
abstract = "Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APP(swe)/PS1(dE9) transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis, and spontaneous alternation behaviour, a measure of spatial working memory, in transgenic mice. We observed no difference in granular neurons between transgenic and wild type mice up till 18 months of age, and no differences with age in wild type mice. The number of neuroblasts and the performance in the spontaneous alternation task was reduced in aged transgenic mice. Paroxetine treatment from 9 to 18 months of age reduced hippocampal amyloidosis without affecting the number of neuroblasts or granular neurons. These findings suggest that the amyloidosis affects the differentiation of neuroblasts and spatial working memory, independent of changes in total granular neurons. Furthermore, while long-term paroxetine treatment may be able to reduce hippocampal amyloidosis, it appears to have no effect on total number of granular neurons or spatial working memory. (C) 2017 Elsevier Inc. All rights reserved.",
keywords = "Aging/genetics, Alzheimer Disease/drug therapy, Amyloid beta-Peptides/metabolism, Amyloid beta-Protein Precursor/genetics, Animals, Bromodeoxyuridine/metabolism, Cytochrome P-450 CYP2D6 Inhibitors/therapeutic use, Dentate Gyrus/drug effects, Disease Models, Animal, Exploratory Behavior/drug effects, Maze Learning/drug effects, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins/metabolism, Mutation/genetics, Neural Stem Cells/drug effects, Neurogenesis/drug effects, Neurons/drug effects, Neuropeptides/metabolism, Paroxetine/therapeutic use, Presenilin-1/genetics",
author = "Olesen, {Louise Orum} and Mithula Sivasaravanaparan and Maurizio Severino and Babcock, {Alicia A.} and Bouzinova, {Elena V.} and West, {Mark J.} and Ove Wiborg and Bente Finsen",
note = "Correction to this article: https://doi.org/10.1016/j.nbd.2019.01.021",
year = "2017",
month = aug,
doi = "10.1016/j.nbd.2017.04.021",
language = "English",
volume = "104",
pages = "50--60",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press",

}

RIS

TY - JOUR

T1 - Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APP(swe)/PS1(dE9) transgenic mice

T2 - Effect of long-term treatment with paroxetine

AU - Olesen, Louise Orum

AU - Sivasaravanaparan, Mithula

AU - Severino, Maurizio

AU - Babcock, Alicia A.

AU - Bouzinova, Elena V.

AU - West, Mark J.

AU - Wiborg, Ove

AU - Finsen, Bente

N1 - Correction to this article: https://doi.org/10.1016/j.nbd.2019.01.021

PY - 2017/8

Y1 - 2017/8

N2 - Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APP(swe)/PS1(dE9) transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis, and spontaneous alternation behaviour, a measure of spatial working memory, in transgenic mice. We observed no difference in granular neurons between transgenic and wild type mice up till 18 months of age, and no differences with age in wild type mice. The number of neuroblasts and the performance in the spontaneous alternation task was reduced in aged transgenic mice. Paroxetine treatment from 9 to 18 months of age reduced hippocampal amyloidosis without affecting the number of neuroblasts or granular neurons. These findings suggest that the amyloidosis affects the differentiation of neuroblasts and spatial working memory, independent of changes in total granular neurons. Furthermore, while long-term paroxetine treatment may be able to reduce hippocampal amyloidosis, it appears to have no effect on total number of granular neurons or spatial working memory. (C) 2017 Elsevier Inc. All rights reserved.

AB - Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APP(swe)/PS1(dE9) transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis, and spontaneous alternation behaviour, a measure of spatial working memory, in transgenic mice. We observed no difference in granular neurons between transgenic and wild type mice up till 18 months of age, and no differences with age in wild type mice. The number of neuroblasts and the performance in the spontaneous alternation task was reduced in aged transgenic mice. Paroxetine treatment from 9 to 18 months of age reduced hippocampal amyloidosis without affecting the number of neuroblasts or granular neurons. These findings suggest that the amyloidosis affects the differentiation of neuroblasts and spatial working memory, independent of changes in total granular neurons. Furthermore, while long-term paroxetine treatment may be able to reduce hippocampal amyloidosis, it appears to have no effect on total number of granular neurons or spatial working memory. (C) 2017 Elsevier Inc. All rights reserved.

KW - Aging/genetics

KW - Alzheimer Disease/drug therapy

KW - Amyloid beta-Peptides/metabolism

KW - Amyloid beta-Protein Precursor/genetics

KW - Animals

KW - Bromodeoxyuridine/metabolism

KW - Cytochrome P-450 CYP2D6 Inhibitors/therapeutic use

KW - Dentate Gyrus/drug effects

KW - Disease Models, Animal

KW - Exploratory Behavior/drug effects

KW - Maze Learning/drug effects

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Microtubule-Associated Proteins/metabolism

KW - Mutation/genetics

KW - Neural Stem Cells/drug effects

KW - Neurogenesis/drug effects

KW - Neurons/drug effects

KW - Neuropeptides/metabolism

KW - Paroxetine/therapeutic use

KW - Presenilin-1/genetics

U2 - 10.1016/j.nbd.2017.04.021

DO - 10.1016/j.nbd.2017.04.021

M3 - Journal article

C2 - 28461249

VL - 104

SP - 50

EP - 60

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

ER -