Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression

Patrick H. Lim, Stephanie L. Wert, Elif Tunc-Ozcan, Robert Marr, Adriana B Ferreira, Eva Redei

Research output: Contribution to journalArticle

Abstract

Aging and major depressive disorder are risk factors for dementia, including Alzheimer's Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs. This deficit, measured as duration of freezing in the fear provoking-context was not related to activity differences between the strains prior to fear conditioning. Hippocampal expression of AD-related genes, such as amyloid precursor protein, amyloid beta 42, beta secretase, synucleins, total and dephosphorylated tau, and synaptophysin, did not differ between WLIs and WMIs in either age group. However, hippocampal transcript levels of catalase (Cat) and hippocampal and frontal cortex expression of insulin-like growth factor 2 (Igf2) and Igf2 receptor (Igf2r) paralleled fear memory differences between middle-aged WLIs and WMIs. This data suggests that chronic depression-like behavior that is present in this genetic model is a risk factor for early spatial memory decline in females. The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model.

Original languageEnglish (US)
Pages (from-to)242-249
Number of pages8
JournalBehavioural Brain Research
Volume353
DOIs
StatePublished - Nov 1 2018

Fingerprint

Genetic Models
Hippocampus
Depression
Fear
Alzheimer Disease
Dementia
Synucleins
Genetic Phenomena
Somatomedin Receptors
Amyloid Precursor Protein Secretases
Synaptophysin
Amyloid beta-Protein Precursor
Memory Disorders
Major Depressive Disorder
Frontal Lobe
Somatomedins
Amyloid
Catalase
Freezing
Age Groups

Keywords

  • Contextual fear conditioning
  • Insulin-like growth factor 2
  • Insulin-like growth factor 2 receptor
  • Memory
  • Wistar Kyoto More Immobile rat

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

@article{b34a50eb7d8c4099ad37716dece99154,
title = "Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression",
abstract = "Aging and major depressive disorder are risk factors for dementia, including Alzheimer's Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs. This deficit, measured as duration of freezing in the fear provoking-context was not related to activity differences between the strains prior to fear conditioning. Hippocampal expression of AD-related genes, such as amyloid precursor protein, amyloid beta 42, beta secretase, synucleins, total and dephosphorylated tau, and synaptophysin, did not differ between WLIs and WMIs in either age group. However, hippocampal transcript levels of catalase (Cat) and hippocampal and frontal cortex expression of insulin-like growth factor 2 (Igf2) and Igf2 receptor (Igf2r) paralleled fear memory differences between middle-aged WLIs and WMIs. This data suggests that chronic depression-like behavior that is present in this genetic model is a risk factor for early spatial memory decline in females. The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model.",
keywords = "Contextual fear conditioning, Insulin-like growth factor 2, Insulin-like growth factor 2 receptor, Memory, Wistar Kyoto More Immobile rat",
author = "Lim, {Patrick H.} and Wert, {Stephanie L.} and Elif Tunc-Ozcan and Robert Marr and Ferreira, {Adriana B} and Eva Redei",
year = "2018",
month = "11",
day = "1",
doi = "10.1016/j.bbr.2018.02.030",
language = "English (US)",
volume = "353",
pages = "242--249",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier",

}

Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression. / Lim, Patrick H.; Wert, Stephanie L.; Tunc-Ozcan, Elif; Marr, Robert; Ferreira, Adriana B; Redei, Eva.

In: Behavioural Brain Research, Vol. 353, 01.11.2018, p. 242-249.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression

AU - Lim, Patrick H.

AU - Wert, Stephanie L.

AU - Tunc-Ozcan, Elif

AU - Marr, Robert

AU - Ferreira, Adriana B

AU - Redei, Eva

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Aging and major depressive disorder are risk factors for dementia, including Alzheimer's Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs. This deficit, measured as duration of freezing in the fear provoking-context was not related to activity differences between the strains prior to fear conditioning. Hippocampal expression of AD-related genes, such as amyloid precursor protein, amyloid beta 42, beta secretase, synucleins, total and dephosphorylated tau, and synaptophysin, did not differ between WLIs and WMIs in either age group. However, hippocampal transcript levels of catalase (Cat) and hippocampal and frontal cortex expression of insulin-like growth factor 2 (Igf2) and Igf2 receptor (Igf2r) paralleled fear memory differences between middle-aged WLIs and WMIs. This data suggests that chronic depression-like behavior that is present in this genetic model is a risk factor for early spatial memory decline in females. The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model.

AB - Aging and major depressive disorder are risk factors for dementia, including Alzheimer's Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs. This deficit, measured as duration of freezing in the fear provoking-context was not related to activity differences between the strains prior to fear conditioning. Hippocampal expression of AD-related genes, such as amyloid precursor protein, amyloid beta 42, beta secretase, synucleins, total and dephosphorylated tau, and synaptophysin, did not differ between WLIs and WMIs in either age group. However, hippocampal transcript levels of catalase (Cat) and hippocampal and frontal cortex expression of insulin-like growth factor 2 (Igf2) and Igf2 receptor (Igf2r) paralleled fear memory differences between middle-aged WLIs and WMIs. This data suggests that chronic depression-like behavior that is present in this genetic model is a risk factor for early spatial memory decline in females. The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model.

KW - Contextual fear conditioning

KW - Insulin-like growth factor 2

KW - Insulin-like growth factor 2 receptor

KW - Memory

KW - Wistar Kyoto More Immobile rat

UR - http://www.scopus.com/inward/record.url?scp=85042856043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042856043&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2018.02.030

DO - 10.1016/j.bbr.2018.02.030

M3 - Article

VL - 353

SP - 242

EP - 249

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

ER -