Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia

Casey Cook, Judy H. Dunmore, Melissa E Murray, Kristyn Scheffel, Nawsheen Shukoor, Jimei Tong, Monica Castanedes-Casey, Virginia Phillips, Linda Rousseau, Michael S. Penuliar, Aishe Kurti, Dennis W Dickson, Leonard Petrucelli, John D. Fryer

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative tauopathy caused by mutations in the tau gene (MAPT). Individuals with FTDP-17 have deficits in learning, memory, and language, in addition to personality and behavioral changes that are often characterized by a lack of social inhibition. Several transgenic mouse models expressing tau mutations have been tested extensively for memory or motor impairments, though reports of amygdala-dependent behaviors are lacking. To this end, we tested the rTg4510 mouse model on a behavioral battery that included amygdala-dependent tasks of exploration. As expected, rTg4510 mice exhibit profound impairments in hippocampal-dependent learning and memory tests, including contextual fear conditioning. However, rTg4510 mice also display an abnormal hyperexploratory phenotype in the open-field assay, elevated plus maze, light-dark exploration, and cued fear conditioning, indicative of amygdala dysfunction. Furthermore, significant tau burden is detected in the amygdala of both rTg4510 mice and human FTDP-17 patients, suggesting that the rTg4510 mouse model recapitulates the behavioral disturbances and neurodegeneration of the amygdala characteristic of FTDP-17.

Original languageEnglish (US)
Pages (from-to)1769-1777
Number of pages9
JournalNeurobiology of Aging
Volume35
Issue number7
DOIs
StatePublished - Jul 2014

Fingerprint

Frontotemporal Dementia
Amygdala
Transgenic Mice
Fear
Learning
Tauopathies
Chromosomes, Human, Pair 17
Mutation
Personality
Language
Phenotype
Light
Genes

Keywords

  • Amygdala
  • Frontotemporal dementia
  • Neurodegeneration
  • Tau
  • Tauopathy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia. / Cook, Casey; Dunmore, Judy H.; Murray, Melissa E; Scheffel, Kristyn; Shukoor, Nawsheen; Tong, Jimei; Castanedes-Casey, Monica; Phillips, Virginia; Rousseau, Linda; Penuliar, Michael S.; Kurti, Aishe; Dickson, Dennis W; Petrucelli, Leonard; Fryer, John D.

In: Neurobiology of Aging, Vol. 35, No. 7, 07.2014, p. 1769-1777.

Research output: Contribution to journalArticle

Cook, C, Dunmore, JH, Murray, ME, Scheffel, K, Shukoor, N, Tong, J, Castanedes-Casey, M, Phillips, V, Rousseau, L, Penuliar, MS, Kurti, A, Dickson, DW, Petrucelli, L & Fryer, JD 2014, 'Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia', Neurobiology of Aging, vol. 35, no. 7, pp. 1769-1777. https://doi.org/10.1016/j.neurobiolaging.2013.12.023
Cook, Casey ; Dunmore, Judy H. ; Murray, Melissa E ; Scheffel, Kristyn ; Shukoor, Nawsheen ; Tong, Jimei ; Castanedes-Casey, Monica ; Phillips, Virginia ; Rousseau, Linda ; Penuliar, Michael S. ; Kurti, Aishe ; Dickson, Dennis W ; Petrucelli, Leonard ; Fryer, John D. / Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia. In: Neurobiology of Aging. 2014 ; Vol. 35, No. 7. pp. 1769-1777.
@article{03d9368c19134ae29506ab122faa2a91,
title = "Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia",
abstract = "Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative tauopathy caused by mutations in the tau gene (MAPT). Individuals with FTDP-17 have deficits in learning, memory, and language, in addition to personality and behavioral changes that are often characterized by a lack of social inhibition. Several transgenic mouse models expressing tau mutations have been tested extensively for memory or motor impairments, though reports of amygdala-dependent behaviors are lacking. To this end, we tested the rTg4510 mouse model on a behavioral battery that included amygdala-dependent tasks of exploration. As expected, rTg4510 mice exhibit profound impairments in hippocampal-dependent learning and memory tests, including contextual fear conditioning. However, rTg4510 mice also display an abnormal hyperexploratory phenotype in the open-field assay, elevated plus maze, light-dark exploration, and cued fear conditioning, indicative of amygdala dysfunction. Furthermore, significant tau burden is detected in the amygdala of both rTg4510 mice and human FTDP-17 patients, suggesting that the rTg4510 mouse model recapitulates the behavioral disturbances and neurodegeneration of the amygdala characteristic of FTDP-17.",
keywords = "Amygdala, Frontotemporal dementia, Neurodegeneration, Tau, Tauopathy",
author = "Casey Cook and Dunmore, {Judy H.} and Murray, {Melissa E} and Kristyn Scheffel and Nawsheen Shukoor and Jimei Tong and Monica Castanedes-Casey and Virginia Phillips and Linda Rousseau and Penuliar, {Michael S.} and Aishe Kurti and Dickson, {Dennis W} and Leonard Petrucelli and Fryer, {John D.}",
year = "2014",
month = "7",
doi = "10.1016/j.neurobiolaging.2013.12.023",
language = "English (US)",
volume = "35",
pages = "1769--1777",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "7",

}

TY - JOUR

T1 - Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia

AU - Cook, Casey

AU - Dunmore, Judy H.

AU - Murray, Melissa E

AU - Scheffel, Kristyn

AU - Shukoor, Nawsheen

AU - Tong, Jimei

AU - Castanedes-Casey, Monica

AU - Phillips, Virginia

AU - Rousseau, Linda

AU - Penuliar, Michael S.

AU - Kurti, Aishe

AU - Dickson, Dennis W

AU - Petrucelli, Leonard

AU - Fryer, John D.

PY - 2014/7

Y1 - 2014/7

N2 - Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative tauopathy caused by mutations in the tau gene (MAPT). Individuals with FTDP-17 have deficits in learning, memory, and language, in addition to personality and behavioral changes that are often characterized by a lack of social inhibition. Several transgenic mouse models expressing tau mutations have been tested extensively for memory or motor impairments, though reports of amygdala-dependent behaviors are lacking. To this end, we tested the rTg4510 mouse model on a behavioral battery that included amygdala-dependent tasks of exploration. As expected, rTg4510 mice exhibit profound impairments in hippocampal-dependent learning and memory tests, including contextual fear conditioning. However, rTg4510 mice also display an abnormal hyperexploratory phenotype in the open-field assay, elevated plus maze, light-dark exploration, and cued fear conditioning, indicative of amygdala dysfunction. Furthermore, significant tau burden is detected in the amygdala of both rTg4510 mice and human FTDP-17 patients, suggesting that the rTg4510 mouse model recapitulates the behavioral disturbances and neurodegeneration of the amygdala characteristic of FTDP-17.

AB - Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative tauopathy caused by mutations in the tau gene (MAPT). Individuals with FTDP-17 have deficits in learning, memory, and language, in addition to personality and behavioral changes that are often characterized by a lack of social inhibition. Several transgenic mouse models expressing tau mutations have been tested extensively for memory or motor impairments, though reports of amygdala-dependent behaviors are lacking. To this end, we tested the rTg4510 mouse model on a behavioral battery that included amygdala-dependent tasks of exploration. As expected, rTg4510 mice exhibit profound impairments in hippocampal-dependent learning and memory tests, including contextual fear conditioning. However, rTg4510 mice also display an abnormal hyperexploratory phenotype in the open-field assay, elevated plus maze, light-dark exploration, and cued fear conditioning, indicative of amygdala dysfunction. Furthermore, significant tau burden is detected in the amygdala of both rTg4510 mice and human FTDP-17 patients, suggesting that the rTg4510 mouse model recapitulates the behavioral disturbances and neurodegeneration of the amygdala characteristic of FTDP-17.

KW - Amygdala

KW - Frontotemporal dementia

KW - Neurodegeneration

KW - Tau

KW - Tauopathy

UR - http://www.scopus.com/inward/record.url?scp=84903371945&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903371945&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2013.12.023

DO - 10.1016/j.neurobiolaging.2013.12.023

M3 - Article

C2 - 24503275

AN - SCOPUS:84903371945

VL - 35

SP - 1769

EP - 1777

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

IS - 7

ER -