Publications

Latest publication 07/23/2017

Impaired microglia fractalkine signaling affects stress reaction and coping style

Microglia, resident immune cells of the CNS are sensitive to various perturbations of the environment, such as stress exposure, and may be involved...

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    [title] => Impaired microglia fractalkine signaling affects stress reaction and coping style
    [paragraph] => Impaired microglia fractalkine signaling affects stress reaction and coping style in mice
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Authors
Z. Winkler, D. Kuti, S. Ferenczi, K. Gulyás, Á. Polyák, K. Kovács 

 Lab
 Institute of Experimental Medicine, Laboratory of Molecular Neuroendocrinology,Budapest, Hungary 
Journal
Behavioural Brain Research
Abstract
Microglia, resident immune cells of the CNS are sensitive to various perturbations of the environment, such as stress exposure, and may be involved in translating these changes to behavior. Among the pathways mediating stress-related neuronal cues to microglia, the fractalkine-fractalkine receptor (CX3CR1) signaling plays a crucial role. Using mice, in which the CX3CR1 gene was deleted, we explored hormonal and behavioral responses to acute and chronic stress along with changes in hypothalamic microglia. CX3CR1-/- animals display active escape in forced swim- and tail suspension tests, exaggerated neuronal activation in the hypothalamic paraventricular nucleus and increased corticosterone release in response to restraint. Analysis of Iba1 immunostaining of hypothalamic sections revealed stress-related reduction of microglia in CX3CR1-/- mice. Because microglia also contribute to energy balance regulation, we characterized metabolic phenotype of CX3CR1-/- mice. Comparison of respiratory exchange ratio did not show genotype effect on fuel preference, however, the energy expenditure was increased in CX3CR1-/- mice, which may be related to their active coping behavior. Microglia and fractalkine signaling has been repeatedly shown to be involved chronic stress-induced depressive state. CX3CR1-/- mice did not become anhedonic in the two hit chronic stress paradigm, confirming resistance of these animals to chronic stress-induced mood alterations. However, there was no difference in stress hormone levels, open field performance and hypothalamic microglia distribution between the genotypes. These results highlight differential involvement of microglia fractalkine signaling in controlling/integrating hormonal-, metabolic and behavioral responses to acute and chronic stress challenges.
BIOSEB Instruments Used
Tail Suspension Test - Wireless (BIO-TST5)
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Bioseb's version 5 of the Tail Suspension Test system, based on both strain sensors and video acquisition, is the only fully automatic solution in the world for running a simple and objective despair test on mice. It is a fast, painless, and reliable way for testing psychotropic effects from stimulant doses of drugs such as anti-depressants and sedatives. This classic and painless research test for anxiety and depression is now offered with a new, powerful and modern software, in a wireless, bluetooth-based version.

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