Morphological changes in the basolateral amygdala and behavioral disruptions associated with social isolation

Abstract Background Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country’s mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system. Methods Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. Results Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes. Conclusion The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety.

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Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone

Neural Plasticity ◽

10.1155/2015/694347 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Vishvesh H. Shende ◽

Simon McArthur ◽

Glenda E. Gillies ◽

Jolanta Opacka-Juffry

Keyword(s):

Nucleus Accumbens ◽

Basolateral Amygdala ◽

Brain Volume ◽

Dorsal Hippocampus ◽

Morphological Changes ◽

Primary Process ◽

Total Brain Volume ◽

Cell Numbers ◽

Total Brain ◽

Process Length

The long-term effects of antenatal dexamethasone treatment on brain remodelling in 3-month-old male Sprague Dawley rats whose mothers had been treated with dexamethasone were investigated in the present study. Dorsal hippocampus, basolateral amygdala and nucleus accumbens volume, cell numbers, and GFAP-immunoreactive astroglial cell morphology were analysed using stereology. Total brain volume as assessed by micro-CT was not affected by the treatment. The relative volume of the dorsal hippocampus (% of total brain volume) showed a moderate, by 8%, but significant reduction in dexamethasone-treated versus control animals. Dexamethasone had no effect on the total and GFAP-positive cell numbers in the hippocampal subregions, basolateral amygdala, and nucleus accumbens. Morphological analysis indicated that numbers of astroglial primary processes were not affected in any of the hippocampal subregions analysed but significant reductions in the total primary process length were observed in CA1 by 32%, CA3 by 50%, and DG by 25%. Mean primary process length values were also significantly decreased in CA1 by 25%, CA3 by 45%, and DG by 25%. No significant astroglial morphological changes were found in basolateral amygdala and nucleus accumbens. We propose that the dexamethasone-dependent impoverishment of hippocampal astroglial morphology is the case of maladaptive glial plasticity induced prenatally.

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Social isolation-induced effects on male-specific courtship behaviours and dendritic architecture in associative forebrain areas in Zebra finches (Taeniopygia guttata)

Avian Biology Research ◽

10.1177/1758155921997982 ◽

2021 ◽

pp. 175815592199798

Author(s):

Vidya Shukla ◽

Monika Sadananda

Keyword(s):

Social Isolation ◽

Morphological Changes ◽

Taeniopygia Guttata ◽

Zebra Finches ◽

Branch Points ◽

Nest Box ◽

Pair Bonds ◽

Golgi Technique ◽

Socially Isolated ◽

Male Specific

Zebra finches ( Taeniopygia guttata) are highly monogamous birds that maintain lifelong pair-bonds. Females make the mate choice based on the quality of males who initiate pair-bond formation by courting the female. A mate separation-reunion paradigm can help to evaluate the adaptive value of social affiliation of male finches and their affinity to new females in absence of mated females which can manifest at a neuronal level by dendritic measures. The aim of this study was to examine behavioural and neuronal changes as a result of social isolation following pair-bonding in male zebra finches. Towards this, male zebra finches from a pair-bonded group were isolated for a period of ten days and then exposed to either the mate or a new female. Four main courtship behaviours: clumping, allopreening, nest box occupancy and directed singing were recorded and analysed. Brains were processed by a modified Golgi technique to detect changes in dendritic arborizations using the Sholl analysis. Baseline behavioural results showed an increase in clumping and nest box activity by day 10. Isolated males re-introduced with their pair-bonded females demonstrated increased nest box activity. Alternatively, isolated males exposed to new females demonstrated increased directed singing when compared to their pair-bonded state, but lower than when exposed to same female. Neuro-morphological changes assessed through quantification of dendritic intersections and branch points were observed in pallial brain areas known to be implicated in the development of social/sexual preferences, with the pair-bonded group demonstrating more branching and longer dendrites when compared to the socially-isolated group. Thus social isolation impacts both courtship behaviour and neuronal morphologies with differential responses to the pair-bonded female versus a new female.

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Chronic social isolation during adolescence augments catecholamine response to acute ethanol in the basolateral amygdala

Synapse ◽

10.1002/syn.21826 ◽

2015 ◽

Vol 69 (8) ◽

pp. 385-395 ◽

Cited By ~ 26

Author(s):

Anushree N. Karkhanis ◽

Nancy J. Alexander ◽

Brian A. McCool ◽

Jeffrey L. Weiner ◽

Sara R. Jones

Keyword(s):

Social Isolation ◽

Basolateral Amygdala ◽

Catecholamine Response ◽

Acute Ethanol

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Adolescent social isolation enhances the plasmalemmal density of NMDA NR1 subunits in dendritic spines of principal neurons in the basolateral amygdala of adult mice

Neuroscience ◽

10.1016/j.neuroscience.2013.11.003 ◽

2014 ◽

Vol 258 ◽

pp. 174-183 ◽

Cited By ~ 16

Author(s):

J.O. Gan ◽

E. Bowline ◽

F.S. Lourenco ◽

V.M. Pickel

Keyword(s):

Social Isolation ◽

Dendritic Spines ◽

Basolateral Amygdala ◽

Adult Mice

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Social Isolation Induces Neuroinflammation And Microglia Overactivation, While Dihydromyricetin Prevents And Improves Them.

10.21203/rs.3.rs-923871/v1 ◽

2021 ◽

Author(s):

Alzahra J Al Omran ◽

Amy S Shao ◽

Saki Watanabe ◽

Zeyu Zhang ◽

Jifeng Zhang ◽

...

Keyword(s):

Social Isolation ◽

Mental Health Treatment ◽

Morphological Changes ◽

Signal Transmission ◽

Corticosterone Level ◽

Treatment Resistance ◽

Mental Illnesses ◽

Serum Corticosterone ◽

Pathway Activation ◽

Socially Isolated

Abstract Background: Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country's mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment-resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system.Methods: Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety like behaviors after DHM treatment were examined using elevated plus maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. Results: Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation also induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes.Conclusion: The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to restore neuroinflammatory changes induced by anxiety.

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Adolescent social isolation rearing impaired social behavior and synaptic function in basolateral amygdala in mice

Proceedings for Annual Meeting of The Japanese Pharmacological Society ◽

10.1254/jpssuppl.93.0_2-p-169 ◽

2020 ◽

Vol 93 (0) ◽

pp. 2-P-169

Author(s):

Hiroshi Kuniishi ◽

Yuko Nakatake ◽

Masayuki Sekiguchi ◽

Mitsuhiko Yamada

Keyword(s):

Social Behavior ◽

Social Isolation ◽

Basolateral Amygdala ◽

Synaptic Function ◽

Isolation Rearing ◽

Social Isolation Rearing

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Electroencephalographic changes and testosterone levels in a pubertal stress animal model: effects on adult sexual motivation

Salud Mental ◽

10.17711/sm.0185-3325.2020.003 ◽

2020 ◽

Vol 43 (1) ◽

pp. 11-19

Author(s):

Marisela Hernández González ◽

Enrique Hernández Arteaga ◽

Miguel Ángel Guevara ◽

Herlinda Bonilla Jaime ◽

Marcela Arteaga Silva

Keyword(s):

Social Isolation ◽

Basolateral Amygdala ◽

Serum Testosterone ◽

Sexual Motivation ◽

Brain Structures ◽

Male Rats ◽

Control Group ◽

Long Term Effects ◽

Testosterone Levels ◽

Eeg Activation

Introduction. Stress during puberty exerts long-term effects on endocrine systems and brain structures, such as the prefrontal cortex (PFC) and basolateral amygdala (BLA), two cerebral areas that participate in modulating sexual behavior and whose functioning is regulated by androgenic hormones. Objective. To evaluate the effect of pubertal stress due to social isolation on the sexual motivation, serum testosterone levels, and electroencephalographic activity (EEG) of the PFC and BLA in male rats. Method. Sixty sexually-experienced male rats were used. Thirty were stressed by social isolation during puberty (SG, housed 1 per cage, postnatal days 25-50); the other 30 formed the control group (CG, 5 per cage). All rats were implanted bilaterally with stainless steel electrodes in the PFC and BLA. EEGs were recorded during the awake-quiet state in two conditions: without sexual motivation (WSM), and with sexual motivation (SM). After EEG recording, the rats were sacrificed by decapitation to measure their testosterone levels. Results. SG showed lower sexual motivation and testosterone levels, but higher amygdaline EEG activation in the presence of a receptive female, while CG showed higher prefrontal EEG activation. Discussion and conclusion. It is probable that the decreased testosterone levels resulting from pubertal stress affected prefrontal and amygdaline functionality and, hence, sexual motivation. These data could explain some of the hormonal and cerebral changes associated with stress-induced sexual alterations, though this suggestion requires additional clinical and animal research.

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