Effects of social isolation and re-socialization on cognition and ADAR1 (p110) expression in mice

A lot of literature show that social isolation stress could be a key reason that leads to cognitive deficits for both humans and rodent models; however, the detailed mechanisms are still not clear completely. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We hypothesize that social isolation stress may impact the expression of ADAR1, leading to cognitive deficits. To prove our hypothesis, we evaluated the cognition ability of the mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expressions in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress significantly induced spatial and non-spatial cognition deficits. In addition, social isolation significantly increased both the immuno reactivity and protein expressions of ADAR1 in the hippocampus and frontal cortex. Furthermore, we found that adolescent re-socialization recovered not only the cognition deficits but also the increased ADAR1 protein expression in hippocampus and the increased number of ADAR1 positive cells in frontal cortex of the isolated mice. In conclusion, social isolation stress significantly increased ADAR1 expressions in the hippocampus and cortex, leading to cognitive deficits.

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Social isolation increased ADAR1 expressions leading to cognitive deficits of mice

10.7287/peerj.preprints.1997v1 ◽

2016 ◽

Author(s):

Wei Chen ◽

Dong An ◽

Hong Xu ◽

Xiaoxin Cheng ◽

Shiwei Wang ◽

...

Keyword(s):

Cognitive Function ◽

Frontal Cortex ◽

Social Isolation ◽

Cognitive Deficits ◽

Close Relation ◽

Object Location ◽

Rodent Models ◽

Isolation Stress ◽

Protein Expressions ◽

Social Isolation Stress

A lot of literature show that social isolation stress could be a key reason that leads to cognitive deficits for both humans and rodent models; however, the detailed mechanisms are still not clear completely. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We hypothesize that social isolation stress may impact the expression of ADAR1, leading to cognitive deficits. To prove our hypothesis, we evaluated the cognition ability of the mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expressions in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress significantly induced spatial and non-spatial cognition deficits. In addition, social isolation significantly increased both the immuno reactivity and protein expressions of ADAR1 in the hippocampus and frontal cortex. Furthermore, we found that adolescent re-socialization recovered not only the cognition deficits but also the increased ADAR1 protein expression in hippocampus and the increased number of ADAR1 positive cells in frontal cortex of the isolated mice. In conclusion, social isolation stress significantly increased ADAR1 expressions in the hippocampus and cortex, leading to cognitive deficits.

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Altered ADAR1 in mice affected by social isolation stress-induced cognitive deficits

10.7287/peerj.preprints.1870v1 ◽

2016 ◽

Author(s):

Wei Chen ◽

Dong An ◽

Hong Xu ◽

Xiaoxin Cheng ◽

Shiwei Wang ◽

...

Keyword(s):

Mouse Model ◽

Protein Expression ◽

Western Blot ◽

Frontal Cortex ◽

Adenosine Deaminase ◽

Social Isolation ◽

Cognitive Deficits ◽

Isolation Stress ◽

Social Isolation Stress ◽

Set Up

Adenosine deaminase acting on RNA (ADAR) activity increases in response to inflammation. Social isolation stress is related to neuroinflammation; however, it remains unclear whether ADAR1 is altered in response to social isolation stress-induced cognitive deficits. To investigate our hypothesis that ADAR1 displayed patterns of change in response to social isolation stress, we addressed this issue systemically by isolating Kunming mice for 2, 4 and 8 weeks individually since postnatal 21 days to set up isolation mouse model. Furthermore, we arranged re-socialization group to evaluate the alterations of ADAR1 in the cognitive deficits recovery. The results of behavior tests showed that social isolation stress resulted in cognitive dysfunction, which was recovered by re-socialization in re-gregarious rearing group. Furthermore, the immunohistochemistry and western blot results displayed that both the immunoreactivity and protein expression of ADAR1 in the hippocampus and frontal cortex increased obviously as compared to the same age mice without isolation. The above abnormal alterations of ADAR1 were recovered by re-socialization in re-gregarious rearing group. Our study supports the hypothesis that ADAR1 is altered in mice affected by social isolation stress-induced cognitive deficits.

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Altered ADAR1 in mice affected by social isolation stress-induced cognitive deficits

10.7287/peerj.preprints.1870 ◽

2016 ◽

Author(s):

Wei Chen ◽

Dong An ◽

Hong Xu ◽

Xiaoxin Cheng ◽

Shiwei Wang ◽

...

Keyword(s):

Mouse Model ◽

Protein Expression ◽

Western Blot ◽

Frontal Cortex ◽

Adenosine Deaminase ◽

Social Isolation ◽

Cognitive Deficits ◽

Isolation Stress ◽

Social Isolation Stress ◽

Set Up

Adenosine deaminase acting on RNA (ADAR) activity increases in response to inflammation. Social isolation stress is related to neuroinflammation; however, it remains unclear whether ADAR1 is altered in response to social isolation stress-induced cognitive deficits. To investigate our hypothesis that ADAR1 displayed patterns of change in response to social isolation stress, we addressed this issue systemically by isolating Kunming mice for 2, 4 and 8 weeks individually since postnatal 21 days to set up isolation mouse model. Furthermore, we arranged re-socialization group to evaluate the alterations of ADAR1 in the cognitive deficits recovery. The results of behavior tests showed that social isolation stress resulted in cognitive dysfunction, which was recovered by re-socialization in re-gregarious rearing group. Furthermore, the immunohistochemistry and western blot results displayed that both the immunoreactivity and protein expression of ADAR1 in the hippocampus and frontal cortex increased obviously as compared to the same age mice without isolation. The above abnormal alterations of ADAR1 were recovered by re-socialization in re-gregarious rearing group. Our study supports the hypothesis that ADAR1 is altered in mice affected by social isolation stress-induced cognitive deficits.

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Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine-to-glutamate ratio andmyo-inositol concentration in the mouse frontal cortex

Journal of Neurochemistry ◽

10.1111/jnc.14116 ◽

2017 ◽

Vol 142 (5) ◽

pp. 767-775 ◽

Cited By ~ 7

Author(s):

Alberto Corcoba ◽

Rolf Gruetter ◽

Kim Q. Do ◽

João M.N. Duarte

Keyword(s):

Frontal Cortex ◽

Social Isolation ◽

Isolation Stress ◽

Common Effect ◽

Social Isolation Stress ◽

Glutathione Deficiency

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Social Isolation Stress-Induced Fear Memory Deficit is Mediated by Down-Regulated Neuro-Signaling System and Egr-1 Expression in the Brain

Neurochemical Research ◽

10.1007/s11064-014-1283-5 ◽

2014 ◽

Vol 39 (5) ◽

pp. 875-882 ◽

Cited By ~ 19

Author(s):

Ryo Okada ◽

Kinzo Matsumoto ◽

Ryohei Tsushima ◽

Hironori Fujiwara ◽

Koichi Tsuneyama

Keyword(s):

Social Isolation ◽

Fear Memory ◽

Memory Deficit ◽

Signaling System ◽

Isolation Stress ◽

Social Isolation Stress ◽

The Brain

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Ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf15438-45 ◽

2017 ◽

Vol 15 (4) ◽

pp. 38-45

Author(s):

Petr D Shabanov ◽

Petr M Vinogradov ◽

Andrei A Lebedev ◽

Roman O Roik ◽

Vitalii I Morozov

Keyword(s):

Motor Activity ◽

Social Isolation ◽

Positive Reinforcement ◽

Intranasal Administration ◽

Anxiolytic Effect ◽

Adult Rats ◽

Isolation Stress ◽

Communicative Behavior ◽

Social Isolation Stress ◽

The Brain

Wistar rats were rearing in conditions of social isolation from others beginning with 20th day of life till adulthood (90-100 days). In adult rats, a conditioned place preference (CPP) of ethanol (0.5 g/kg ip) was trained, and behavior in open field, elevated plus maze and intruder-resident test was examined. Intranasal administration of [D-Lys3]-GHRP-6, a peptide ghrelin antagonist (10 µg in 20 µl), to isolated rats blocked formation and expression (recovery) of CPP of ethanol that supported participation of ghrelin system in regulation of positive reinforcement activated by ethanol. Intranasal administration of ghrelin (20 µg in 20 µl) to rats reared in conditions of social isolation produced a typical anxiogenic effect, elevated exploratory activity, aggression signs and reduction of communicative behavior. In rats reared in conditions of social isolation, [D-Lys3]-GHRP-6, a ghrelin antagonist, possessed anxiolytic effect, reduced explorative activity, communicative behavior and aggression. It is concluded that ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress. (For citation: Shabanov PD, Vinogradov PM, Lebedev AA, et al. Ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):38-45. doi: 10.17816/RCF15438-45).

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