Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice

AbstractWhile 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.

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Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice

10.21203/rs.3.rs-44102/v2 ◽

2020 ◽

Author(s):

Dany Arsenault ◽

Cyntia Tremblay ◽

Vincent Emond ◽

Frederic Calon

Keyword(s):

Entorhinal Cortex ◽

Transgene Expression ◽

Indirect Evidence ◽

Cellular Level ◽

Biological Sex ◽

Pulse Ratio ◽

Males And Females ◽

Hyperpolarization Activated Current ◽

Physiological Differences ◽

The Brain

Abstract While the higher prevalence of Alzheimer Disease (AD) is clear, studies suggest that biological sex may also influence its 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 after hyperpolarization (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 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.

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Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice

10.21203/rs.3.rs-44102/v1 ◽

2020 ◽

Author(s):

Dany Arsenault ◽

Cyntia Tremblay ◽

Vincent Emond ◽

Frederic Calon

Keyword(s):

Entorhinal Cortex ◽

Transgene Expression ◽

Indirect Evidence ◽

Cellular Level ◽

Biological Sex ◽

Pulse Ratio ◽

Males And Females ◽

Hyperpolarization Activated Current ◽

Physiological Differences ◽

The Brain

Abstract While the higher prevalence of Alzheimer Disease (AD) is clear, studies suggest that biological sex may also influence its 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 after hyperpolarization (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 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.

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Pseudoneglect of Males and Females on a Spatial Short-Term Memory Task

Perceptual and Motor Skills ◽

10.2466/pms.1997.84.1.99 ◽

1997 ◽

Vol 84 (1) ◽

pp. 99-105 ◽

Cited By ~ 10

Author(s):

Erhan Nalçaci ◽

Metehan Çiçek ◽

Canan Kalaycioglu ◽

Sema Yavuzer

Keyword(s):

Short Term Memory ◽

Memory Task ◽

Indirect Evidence ◽

Spatial Task ◽

Strongly Correlated ◽

Short Term ◽

Significant Difference ◽

Males And Females ◽

The Right ◽

The Brain

The effect of sex on the phenomenon of pseudoneglect was assessed in 60 male and 61 female right-handed subjects using a modified form of Corsi's block-tapping test. A significant right-lateralized pseudoneglect for both sexes was found, and the level of pseudoneglect strongly correlated with neglect in the right hemispace. Men were significantly more accurate in the left hemispace than women, whereas no difference was seen between the sexes in the right hemispace. Although we found some indirect evidence from which to infer that the men's brain may be functionally more lateralized than the women's for this spatial task, there was no significant difference between the sexes in correct responses for the left hemispace, i.e., right pseudoneglect. Therefore, the results suggest that pseudoneglect phenomenon can be partly explained by a functional asymmetric feature of the brain, and the other factors probably play a role in producing the similar patterns of asymmetric perception of space in males and females.

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Faculty Opinions recommendation of Transgene expression in the Nop-tTA driver line is not inherently restricted to the entorhinal cortex.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725434247.793506283 ◽

2015 ◽

Author(s):

Jaime Grutzendler

Keyword(s):

Entorhinal Cortex ◽

Transgene Expression ◽

Driver Line

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Stability of Lentiviral Vector-Mediated Transgene Expression in the Brain in the Presence of Systemic Antivector Immune Responses

Human Gene Therapy ◽

10.1089/hum.2005.16.741 ◽

2005 ◽

Vol 16 (6) ◽

pp. 741-751 ◽

Cited By ~ 91

Author(s):

Evelyn Abordo-Adesida ◽

Antonia Follenzi ◽

Carlos Barcia ◽

Sandra Sciascia ◽

Maria G. Castro ◽

...

Keyword(s):

Immune Responses ◽

Transgene Expression ◽

Lentiviral Vector ◽

The Brain

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Müllerian inhibiting substance contributes to sex-linked biases in the brain and behavior

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0902253106 ◽

2009 ◽

Vol 106 (17) ◽

pp. 7203-7208 ◽

Cited By ~ 45

Author(s):

Pei-Yu Wang ◽

Anna Protheroe ◽

Andrew N. Clarkson ◽

Floriane Imhoff ◽

Kyoko Koishi ◽

...

Keyword(s):

Motor Neurons ◽

Reproductive Tract ◽

Behavioral Traits ◽

Spinal Motor Neurons ◽

Müllerian Inhibiting Substance ◽

Males And Females ◽

Brain And Behavior ◽

And Behavior ◽

The Brain ◽

Mullerian Inhibiting Substance

Many behavioral traits and most brain disorders are common to males and females but are more evident in one sex than the other. The control of these subtle sex-linked biases is largely unstudied and has been presumed to mirror that of the highly dimorphic reproductive nuclei. Sexual dimorphism in the reproductive tract is a product of Müllerian inhibiting substance (MIS), as well as the sex steroids. Males with a genetic deficiency in MIS signaling are sexually males, leading to the presumption that MIS is not a neural regulator. We challenge this presumption by reporting that most immature neurons in mice express the MIS-specific receptor (MISRII) and that male Mis−/− and Misrii−/− mice exhibit subtle feminization of their spinal motor neurons and of their exploratory behavior. Consequently, MIS may be a broad regulator of the subtle sex-linked biases in the nervous system.

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DARPP-32 promoter directs transgene expression to renal thick ascending limb of loop of Henle

AJP Renal Physiology ◽

10.1152/ajprenal.1995.269.4.f564 ◽

1995 ◽

Vol 269 (4) ◽

pp. F564-F570 ◽

Cited By ~ 2

Author(s):

S. Blau ◽

L. Daly ◽

A. Fienberg ◽

G. Teitelman ◽

M. E. Ehrlich

Keyword(s):

Transgene Expression ◽

Ectopic Expression ◽

Medium Size ◽

Thick Ascending Limb ◽

Loop Of Henle ◽

Transcription Start Sites ◽

Medullary Thick Ascending Limb ◽

Spiny Neurons ◽

Adult Kidney ◽

The Brain

DARPP-32, a dopamine- and adenosine 3',5'-cyclic monophosphate (cAMP)-regulated inhibitor of protein phosphatase-1, is highly colocalized with neuronal and nonneuronal D1-type receptors. DARPP-32 concentration is enriched in the renal outer medulla and in the medium-size spiny neurons of the brain. In the ascending limb of the loop of Henle, DARPP-32 is phosphorylated following stimulation by dopamine and other first messengers, and in this form inhibits the activity of the Na(+)-K(+)-adenosinetriphosphatase pump. For functional analysis of the DARPP-32 promoter in the kidney, we characterized the murine gene. There are two groups of transcription start sites utilized in the brain, but the proximal set appears to be preferentially used in the kidney. In four of four lines of mice carrying a DARPP-32/lacZ transgene with 2.1 kb of 5'-flanking DNA, adult kidney lacZ transgene expression mimicked that of endogenous DARPP-32. There was no ectopic expression in peripheral organs. We conclude that the sequences necessary for direction of DARPP-32 expression to the medullary thick ascending limb are contained within this 2.1-kb fragment.

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Sex differences in neural and behavioral signatures of cooperation revealed by fNIRS hyperscanning

Scientific Reports ◽

10.1038/srep26492 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 57

Author(s):

Joseph M. Baker ◽

Ning Liu ◽

Xu Cui ◽

Pascal Vrticka ◽

Manish Saggar ◽

...

Keyword(s):

Sex Differences ◽

Temporal Cortex ◽

Neural Correlates ◽

Behavioral Signatures ◽

Computer Based ◽

Males And Females ◽

Brain And Behavior ◽

The Right ◽

And Behavior ◽

The Brain

Abstract Researchers from multiple fields have sought to understand how sex moderates human social behavior. While over 50 years of research has revealed differences in cooperation behavior of males and females, the underlying neural correlates of these sex differences have not been explained. A missing and fundamental element of this puzzle is an understanding of how the sex composition of an interacting dyad influences the brain and behavior during cooperation. Using fNIRS-based hyperscanning in 111 same- and mixed-sex dyads, we identified significant behavioral and neural sex-related differences in association with a computer-based cooperation task. Dyads containing at least one male demonstrated significantly higher behavioral performance than female/female dyads. Individual males and females showed significant activation in the right frontopolar and right inferior prefrontal cortices, although this activation was greater in females compared to males. Female/female dyad’s exhibited significant inter-brain coherence within the right temporal cortex, while significant coherence in male/male dyads occurred in the right inferior prefrontal cortex. Significant coherence was not observed in mixed-sex dyads. Finally, for same-sex dyads only, task-related inter-brain coherence was positively correlated with cooperation task performance. Our results highlight multiple important and previously undetected influences of sex on concurrent neural and behavioral signatures of cooperation.

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Multifaceted origins of sex differences in the brain

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2015.0106 ◽

2016 ◽

Vol 371 (1688) ◽

pp. 20150106 ◽

Cited By ~ 71

Author(s):

Margaret M. McCarthy

Keyword(s):

Sex Differences ◽

State Of The Art ◽

Human Subjects ◽

Special Issue ◽

Molecular Analyses ◽

The Past ◽

Current State ◽

Biological Variable ◽

Males And Females ◽

The Brain

Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue.

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