CYTOKINE CONTENT WITHIN BRAIN STRUCTURES IN RATS WITH GENETIC PREDISPOSITION TO DIFFERENT LEVELS OF AGGRESSION

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Abstract

Introduction. There is increasing evidence that altered neuroimmune responses are implicated in the neurobiology of aggression, including the production of pro- and anti-inflammatory cytokines. However, little is known about brain cytokine changes and their regional characteristics in animals genetically selected for either high or low aggressive behaviors. Materials and methods. In the present study the content of cytokines (IL-1β, IL-2, IL-6, TNFα, IL-10) was measured by ELISA method in the brain structures (the hypothalamus, striatum, frontal cortex, and hippocampus) in two rat lines selected for differences in fear-induced aggression at 2, 4, and 24 h after a peripheral injection of saline or lipopolysaccharide (LPS, 250 µg/kg). Results and discussions. LPS stimulation elevated cytokine activity above baseline levels in both aggressive and nonaggressive rats, but the pattern, time course of cytokine changes, and their regional characteristics varied according to the aggressiveness of the animals. After LPS administration, aggressive rats showed increased levels of IL-1β in the hypothalamus at 2 and 4 h and in the frontal cortex at 4 and 24 h compared to LPS-treated nonaggressive line. IL-2 was increased in the frontal cortex and striatum of aggressive rats within 24 h, while IL-6 elevation in the hypothalamus was found at 4 h and in the frontal cortex at 2 and 4 h. In the hippocampus, the levels of IL-1β, IL-2, and IL-6 were lower in LPS-treated aggressive rats than in nonaggressive animals. The levels of anti-inflammatory cytokine IL-10 were also decreased in all brain structures of aggressive rats receiving LPS. Conclusion. The present data indicate that genetic predisposition to increased aggressiveness is associated with region-specific changes in the content of pro- and anti-inflammatory cytokines and their variations over time in the brain structures.

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Introduction. There is increasing evidence that altered neuroimmune responses are implicated in the neurobiology of aggression, including the production of pro- and anti-inflammatory cytokines. However, little is known about brain cytokine changes and their regional characteristics in animals genetically selected for either high or low aggressive behaviors. Materials and methods. In the present study the content of cytokines (IL-1β, IL-2, IL-6, TNFα, IL-10) was measured by ELISA method in the brain structures (the hypothalamus, striatum, frontal cortex, and hippocampus) in two rat lines selected for differences in fear-induced aggression at 2, 4, and 24 h after a peripheral injection of saline or lipopolysaccharide (LPS, 250 µg/kg). Results and discussions. LPS stimulation elevated cytokine activity above baseline levels in both aggressive and nonaggressive rats, but the pattern, time course of cytokine changes, and their regional characteristics varied according to the aggressiveness of the animals. After LPS administration, aggressive rats showed increased levels of IL-1β in the hypothalamus at 2 and 4 h and in the frontal cortex at 4 and 24 h compared to LPS-treated nonaggressive line. IL-2 was increased in the frontal cortex and striatum of aggressive rats within 24 h, while IL-6 elevation in the hypothalamus was found at 4 h and in the frontal cortex at 2 and 4 h. In the hippocampus, the levels of IL-1β, IL-2, and IL-6 were lower in LPS-treated aggressive rats than in nonaggressive animals. The levels of anti-inflammatory cytokine IL-10 were also decreased in all brain structures of aggressive rats receiving LPS. Conclusion. The present data indicate that genetic predisposition to increased aggressiveness is associated with region-specific changes in the content of pro- and anti-inflammatory cytokines and their variations over time in the brain structures. Keywords: genetically defined fear-induced aggression; brain structures; pro- and anti-inflammatory cytokines; LPS.
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About the authors

E L Alperina

Scientific Research Institute of Physiology and Basic Medicine

E N Zhukova

Scientific Research Institute of Physiology and Basic Medicine

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Copyright (c) 2019 Alperina E.L., Zhukova E.N.

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