Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice
Abstract While the higher prevalence of Alzheimer’s disease (AD) in women is clear, studies suggest that biological sex may also influence AD pathogenesis. However, mechanisms behind these differences are not clear. To investigate physiological differences between sexes at the cellular level in the...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2020-11-01
|
Series: | Biology of Sex Differences |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s13293-020-00337-0 |
id |
doaj-6942848ad44648d49e14473b8bb15037 |
---|---|
record_format |
Article |
spelling |
doaj-6942848ad44648d49e14473b8bb150372020-11-25T04:11:55ZengBMCBiology of Sex Differences2042-64102020-11-0111111910.1186/s13293-020-00337-0Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD miceDany Arsenault0Cyntia Tremblay1Vincent Emond2Frédéric Calon3Faculty of Pharmacy, Université LavalNeuroscience, Centre de Recherche du CHU de Québec (CHUQ)Neuroscience, Centre de Recherche du CHU de Québec (CHUQ)Faculty of Pharmacy, Université LavalAbstract While the higher prevalence of Alzheimer’s disease (AD) in women is clear, studies suggest that biological sex may also influence AD pathogenesis. However, mechanisms behind these differences are not clear. To investigate physiological differences between sexes at the cellular level in the brain, we investigated the intrinsic and synaptic properties of entorhinal cortex neurons in heterozygous 3xTg-AD mice of both sexes at the age of 20 months. This brain region was selected because of its early association with AD symptoms. First, we found physiological differences between male and female non-transgenic mice, providing indirect evidence of axonal alterations in old females. Second, we observed a transgene-dependent elevation of the firing activity, post-burst afterhyperpolarization (AHP), and spontaneous excitatory postsynaptic current (EPSC) activity, without any effect of sex. Third, the passive properties and the hyperpolarization-activated current (Ih) were altered by transgene expression only in female mice, whereas the paired-pulse ratio (PPR) of evoked EPSC was changed only in males. Fourth, both sex and transgene expression were associated with changes in action potential properties. Consistent with previous work, higher levels of Aβ neuropathology were detected in 3xTg-AD females, whereas tau deposition was similar. In summary, our results support the idea that aging and AD neuropathology differentially alter the physiology of entorhinal cortex neurons in males and females.http://link.springer.com/article/10.1186/s13293-020-00337-0AlzheimerAgingEntorhinal cortex3xTg-AD miceElectrophysiology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dany Arsenault Cyntia Tremblay Vincent Emond Frédéric Calon |
spellingShingle |
Dany Arsenault Cyntia Tremblay Vincent Emond Frédéric Calon Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice Biology of Sex Differences Alzheimer Aging Entorhinal cortex 3xTg-AD mice Electrophysiology |
author_facet |
Dany Arsenault Cyntia Tremblay Vincent Emond Frédéric Calon |
author_sort |
Dany Arsenault |
title |
Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice |
title_short |
Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice |
title_full |
Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice |
title_fullStr |
Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice |
title_full_unstemmed |
Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice |
title_sort |
sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xtg-ad mice |
publisher |
BMC |
series |
Biology of Sex Differences |
issn |
2042-6410 |
publishDate |
2020-11-01 |
description |
Abstract While the higher prevalence of Alzheimer’s disease (AD) in women is clear, studies suggest that biological sex may also influence AD pathogenesis. However, mechanisms behind these differences are not clear. To investigate physiological differences between sexes at the cellular level in the brain, we investigated the intrinsic and synaptic properties of entorhinal cortex neurons in heterozygous 3xTg-AD mice of both sexes at the age of 20 months. This brain region was selected because of its early association with AD symptoms. First, we found physiological differences between male and female non-transgenic mice, providing indirect evidence of axonal alterations in old females. Second, we observed a transgene-dependent elevation of the firing activity, post-burst afterhyperpolarization (AHP), and spontaneous excitatory postsynaptic current (EPSC) activity, without any effect of sex. Third, the passive properties and the hyperpolarization-activated current (Ih) were altered by transgene expression only in female mice, whereas the paired-pulse ratio (PPR) of evoked EPSC was changed only in males. Fourth, both sex and transgene expression were associated with changes in action potential properties. Consistent with previous work, higher levels of Aβ neuropathology were detected in 3xTg-AD females, whereas tau deposition was similar. In summary, our results support the idea that aging and AD neuropathology differentially alter the physiology of entorhinal cortex neurons in males and females. |
topic |
Alzheimer Aging Entorhinal cortex 3xTg-AD mice Electrophysiology |
url |
http://link.springer.com/article/10.1186/s13293-020-00337-0 |
work_keys_str_mv |
AT danyarsenault sexdependentalterationsinthephysiologyofentorhinalcortexneuronsinoldheterozygous3xtgadmice AT cyntiatremblay sexdependentalterationsinthephysiologyofentorhinalcortexneuronsinoldheterozygous3xtgadmice AT vincentemond sexdependentalterationsinthephysiologyofentorhinalcortexneuronsinoldheterozygous3xtgadmice AT fredericcalon sexdependentalterationsinthephysiologyofentorhinalcortexneuronsinoldheterozygous3xtgadmice |
_version_ |
1724416488689893376 |