Post-weaning Social Isolation in Male and Female Prairie Voles: Impacts on Central and Peripheral Immune System

The socially monogamous prairie vole (Microtus ochrogaster) offers a unique opportunity to examine the impacts of adolescent social isolation on the brain, immune system, and behavior. In the current study, male and female prairie voles were randomly assigned to be housed alone or with a same-sex cagemate after weaning (i.e., on postnatal day 21–22) for a 6-week period. Thereafter, subjects were tested for anxiety-like and depressive-like behaviors using the elevated plus maze (EPM) and Forced Swim Test (FST), respectively. Blood was collected to measure peripheral cytokine levels, and brain tissue was processed for microglial density in various brain regions, including the Nucleus Accumbens (NAcc), Medial Amygdala (MeA), Central Amygdala (CeA), Bed Nucleus of the Stria Terminalis (BNST), and Paraventricular Nucleus of the Hypothalamus (PVN). Sex differences were found in EPM and FST behaviors, where male voles had significantly lower total arm entries in the EPM as well as lower latency to immobility in the FST compared to females. A sex by treatment effect was found in peripheral IL-1β levels, where isolated males had a lower level of IL-1β compared to cohoused females. Post-weaning social isolation also altered microglial density in a brain region-specific manner. Isolated voles had higher microglial density in the NAcc, MeA, and CeA, but lower microglial density in the dorsal BNST. Cohoused male voles also had higher microglial density in the PVN compared to cohoused females. Taken together, these data suggest that post-weaning social housing environments can alter peripheral and central immune systems in prairie voles, highlighting a potential role for the immune system in shaping isolation-induced alterations to the brain and behavior.

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Acute social isolation alters neurogenomic state in songbird forebrain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1820841116 ◽

2019 ◽

Vol 117 (38) ◽

pp. 23311-23316 ◽

Cited By ~ 2

Author(s):

Julia M. George ◽

Zachary W. Bell ◽

Daniel Condliffe ◽

Kirstin Dohrer ◽

Teresa Abaurrea ◽

...

Keyword(s):

Gene Expression ◽

Social Isolation ◽

Axonal Guidance ◽

Sequencing Analysis ◽

Negative Effects ◽

Auditory Forebrain ◽

Gene Sets ◽

Brain And Behavior ◽

And Behavior ◽

The Brain

Prolonged social isolation has negative effects on brain and behavior in humans and other social organisms, but neural mechanisms leading to these effects are not understood. Here we tested the hypothesis that even brief periods of social isolation can alter gene expression and DNA methylation in higher cognitive centers of the brain, focusing on the auditory/associative forebrain of the highly social zebra finch. Using RNA sequencing, we first identified genes that individually increase or decrease expression after isolation and observed general repression of gene sets annotated for neurotrophin pathways and axonal guidance functions. We then pursued 4 genes of large effect size: EGR1 and BDNF (decreased by isolation) and FKBP5 and UTS2B (increased). By in situ hybridization, each gene responded in different cell subsets, arguing against a single cellular mechanism. To test whether effects were specific to the social component of the isolation experience, we compared gene expression in birds isolated either alone or with a single familiar partner. Partner inclusion ameliorated the effect of solo isolation on EGR1 and BDNF, but not on FKBP5 and UTS2B nor on circulating corticosterone. By bisulfite sequencing analysis of auditory forebrain DNA, isolation caused changes in methylation of a subset of differentially expressed genes, including BDNF. Thus, social isolation has rapid consequences on gene activity in a higher integrative center of the brain, triggering epigenetic mechanisms that may influence processing of ongoing experience.

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Duration of Social Isolation Affects Production of Nitric Oxide in the Rat Brain

International Journal of Molecular Sciences ◽

10.3390/ijms221910340 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10340

Author(s):

Stanislava Vrankova ◽

Zuzana Galandakova ◽

Jakub Benko ◽

Martina Cebova ◽

Igor Riecansky ◽

...

Keyword(s):

Nitric Oxide ◽

Cerebral Cortex ◽

Social Isolation ◽

No Production ◽

Sprague Dawley ◽

Subsequent Increase ◽

Sprague Dawley Rats ◽

Brain And Behavior ◽

And Behavior ◽

The Brain

Social isolation deprives rodents of social interactions that are critical for normal development of brain and behavior. Several studies have indicated that postweaning isolation rearing may affect nitric oxide (NO) production. The aim of this study was to compare selected behavioral and biochemical changes related to NO production in the brain of rats reared in social isolation for different duration. At the age of 21 days, male Sprague Dawley rats were randomly assigned into four groups reared in isolation or socially for 10 or 29 weeks. At the end of the rearing, open-field and prepulse inhibition (PPI) tests were carried out. Furthermore, in several brain areas we assessed NO synthase (NOS) activity, protein expression of nNOS and iNOS isoforms and the concentration of conjugated dienes (CD), a marker of oxidative damage and lipid peroxidation. Social isolation for 10 weeks resulted in a significant decrease in PPI, which was accompanied by a decrease in NOS activity in the cerebral cortex and the cerebellum, an increase in iNOS in the hippocampus and an increase in CD concentration in cortex homogenate. On the other hand, a 29 week isolation had an opposite effect on NOS activity, which increased in the cerebral cortex and the cerebellum in animals reared in social isolation, accompanied by a decrease in CD concentration. The decrease in NOS activity after 10 weeks of isolation might have been caused by chronic stress induced by social isolation, which has been documented in previous studies. The increased oxidative state might result in the depleted NO bioavailability, as NO reacts with superoxide radical creating peroxynitrite. After 29 weeks of isolation, this loss of NO might be compensated by the subsequent increase in NOS activity.

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Epilepsy: A Stigma More than Disease

Annals of Advanced Biomedical Sciences ◽

10.23880/aabsc-16000131 ◽

2019 ◽

Vol 2 (1) ◽

Author(s):

Rana Khalid Iqbal

Keyword(s):

Genetic Basis ◽

Neurodevelopmental Disorder ◽

Health Conditions ◽

Attitudes And Beliefs ◽

Negative Attitudes ◽

Male And Female ◽

Ancient Times ◽

Brain And Behavior ◽

And Behavior ◽

The Brain

Epilepsy is a common neurological disorder that occurs from ancient times and accompanying with convulsions or seizures. Epilepsy has revealed a genetic basis. Epilepsy which is considered as a neurodevelopmental disorder has reduced the life expectancy and associated with various stigmatized attitudes or beliefs. Epilepsy and seizures can develop in any person both in male and female at any age. Head trauma and brain strokes are the major causes of epilepsy in adults. Epilepsy accompanied by changes in behavior, personality, and cognition. Several aspects of epilepsy can affect the brain and behavior. Stigma is a reality for a lot of people with a mental disorder. It is a mark of disgrace which sets a person apart from others. Negative attitudes and beliefs create prejudice which leads to negative actions and discrimination. Stigma and social exclusions are stereotyped characteristics of epilepsy. Someone with a mental illness known to be a dangerous and senseless rather than saying in poor health conditions. There are no effective cures for an epileptic people. Besides, many epileptic therapies or cures are still available for the diagnosis and prevention of people with epilepsy. Epilepsy treatment entails how epilepsy is treated and which techniques and antiepileptic drugs are used.

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Importance of the immune system in mediating plasticity of the brain and behavior

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2017.06.004 ◽

2017 ◽

Vol 79 ◽

pp. 1-2 ◽

Cited By ~ 2

Author(s):

Li Tian ◽

Marie-Eve Tremblay

Keyword(s):

Immune System ◽

Brain And Behavior ◽

And Behavior ◽

The Brain

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Review of Self-regulation of the Brain and Behavior.

Contemporary Psychology ◽

10.1037/023440 ◽

1985 ◽

Vol 30 (12) ◽

pp. 999-999

Author(s):

Gerald S. Wasserman

Keyword(s):

Self Regulation ◽

Brain And Behavior ◽

And Behavior ◽

The Brain

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Song competition changes the brain and behavior of a male songbird

Journal of Experimental Biology ◽

10.1242/jeb.028456 ◽

2009 ◽

Vol 212 (15) ◽

pp. 2411-2418 ◽

Cited By ~ 7

Author(s):

K. W. Sockman ◽

K. G. Salvante ◽

D. M. Racke ◽

C. R. Campbell ◽

B. A. Whitman

Keyword(s):

Brain And Behavior ◽

And Behavior ◽

The Brain

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The brain and behavior of the fowl

General Pharmacology The Vascular System ◽

10.1016/0306-3623(84)90107-1 ◽

1984 ◽

Vol 15 (2) ◽

pp. 175

Keyword(s):

Brain And Behavior ◽

And Behavior ◽

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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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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