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The role of interleukin 6 in stress response and anxiety-driven behavior in mice

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Aniszewska A., Chlodzinska N., Turlejski K., Djavadian R.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Interleukin 6 (IL-6) plays an important role in stress response and glucocorticoid action on the brain. It has been also shown that IL-6 plays a significant role in physiological and pathological brain development and is a crucial factor in the effects of prenatal immune challenge on physiological and behavioral abnormalities in adult offspring. We examined involvement of IL-6 in stressinduced changes in behavior and brain mechanisms in the adult mice. The PhenoRack system was used to non-invasively monitor mice home cage activity. Behavior of wild type mice C57BL/6J and IL-6 -/- knockout (IL-6 KO) mice were observed for 3 days using the PhenoRack system, which enables non-invasive monitoring of the mice home-cage activity (distance travelled, speeds and duration of movement, freezing). Mice were also subjected to standard behavioral tests. The open field test was used to establish the balance between exploratory behavior and anxiety evoked by the unknown, potentially dangerous situation. We measured the distance travelled in the open part of the arena, as well as time spent in it. We observed the sex-dependent effect of IL-6 on exploratory behavior. In all tested parameters IL-6 deficient females showed less anxiety than the wild type females. There was no difference in behavior in the open field between wild type and IL-6 deficient males. After finishing behavioral tests, the animals were killed with an overdose of pentobarbital and their brains were perfused transcardially with saline (0.9% NaCl) followed by 4% paraformaldehyde in 0.1 M phosphate buffer. The brains were cut on a cryostat into 40 µm sections and collected into 10 parallel series. Two of these series were stained with antibodies against glucocorticoid (GR) and mineralocorticoid (MR) receptors. One series from each brain was Nissl-stained for delineation of borders of the brain structures and evaluation of the number of cells in some of them. The number of hippocampal neurons and GRimmunopositive neurons in an area was estimated using the StereoInvestigator system (MicroBrightField Inc). Due to the crucial role of IL-6 in development of the hippocampus we evaluated the total number of cells in the CA1 field. We found that IL-6- deficient mice had significantly lower number of cells in the CA1 field and that almost all cells, unlike in wild-type mice, expressed the glucocorticoid receptor. Our preliminary results demonstrated that IL-6 is implicated in stress. Supported by the Polish National Science Center grant No 1577

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Interleukin 6 deficiency affects spontaneous activity of mice in age- and sex-dependent manner

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Aniszewska A., Szymanski J., Winnicka M. M., Turlejski K.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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nr 4

We analyzed the role of interleukin 6 (IL-6) in modulation of the pattern of mice spontaneous activity. Wild type (WT) and IL-6 deficient mice of both sexes, young and aging, were housed individually and various types of their activity were recorded and analyzed with the Phenorack system in their home cages during 72 hours-long sessions. All investigated groups of mice were active mainly during the dark phase of the 24-hours cycle. Generally, the IL-6 deficient animals were more active than their WT controls and females of both genotypes more active than males. Aging mice were less active than the sex and genotype-matched young animals. The independent variables (age, sex and genotype) strongly interacted, which suggests that the modulatory influence of IL-6 on mice behavior may be different in males and females and that it changes during aging. We conclude that under normal physiological conditions signaling of IL-6 via its receptor participates in modulation of the basic pattern of activity. This modulation differs in males and females and changes with aging.

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The role of interleukin 6 in behavior of aged mice

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Aniszewska A., Chlodzinska N., Winnicka M., Turlejski K., Djavadian R. L.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr Suppl.1

Interleukin 6 (IL-6) is a cytokine playing an important pleiotropic role in the immune system. IL-6 is also involved in stress response, etiology of the age-related diseases and plays a role of mediator between the central nervous system and the immune system. To study effects of IL-6 on behavior during aging we examined aged (13 to 15 months) IL-6 deficient and wild type (WT) mice. Behavior was tested using the open field test, elevated plus maze test and registration of spontaneous activity in the individual home cages for 72 hours. These registrations showed that IL-6 deficient animals were less active than WT mice. The difference was more distinct during the dark phase. Interestingly, in the open field IL-6 deficient mice displayed higher locomotor activity than control WT mice and spent more time in the central part of the arena. In the elevated plus maze IL-6 deficient mice spent more time exploring open arms than WT mice. We conclude that IL-6 deficient aging animals show lower level of anxiety than WT control animals. After tests mice were perfused and brains were cut into 40 μm sections. Brain sections were immunohistochemically labeled for IL-6 and its receptor (IL-6R), also known as CD126. We found that cells immunopositive for both IL-6 and CD126 were present in the hippocampus and other brain structures. Supported by the National Science Center grant No 1577.

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Adult neurogenesis in opossums and hippocampal-dependent learning

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Tepper B., Aniszewska A., Bartkowska K., Grochocka L., Turlejski K., Djavadian R.

Acta Neurobiologiae Experimentalis

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2019

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tom 79

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nr Suppl.1

INTRODUCTION: Adult hippocampal neurogenesis occurs in many mammalian species, including the laboratory opossum (Monodelphis domestica). Newborn neurons in the dentate gyrus (DG) of the hippocampal formation are involved in learning and spatial memory.The rate of neurogenesis decreases with aging, which was suggested as the cause of the deterioration of cognitive functions. AIM(S): The aim of the study was to examine association between adult neurogenesis in the DG and spatial memory in young and aged opossums METHOD(S): To understand whether new neurons contribute to learning and memory, we performed experiments on young and aged laboratory opossums using the Morris water maze test in which animals learn to locate the hidden platform. After behavioral test, sections from opossum brains were immunostained with doublecortin – a marker of newly born neurons – to investigate the rate of adult neurogenesis in the DG. RESULTS: In the group of young opossums, the time required to find the hidden platform was already significantly lower on the third day of training (vs. day 1, p<0.005), while in aged opossums a significant difference was observed on the fourth day of training (vs. day 1, p<0.02). The level of neurogenesis in the DG of the hippocampal formation was lower in the aged opossums than in the young animals. CONCLUSIONS: However, even the low number of newly formed neurons in the DG of aged opossums are likely to be involved in the formation of spatial memory. FINANCIAL SUPPORT: This research was supported by the National Science Centre Poland, grant number 2015/17/B/NZ4/02410.

Ograniczanie wyników

4 Acta Neurobiologiae Experimentalis

4 Aniszewska A.

4 Turlejski K.

2 Chlodzinska N.

2 Djavadian R.

1 Bartkowska K.

1 Djavadian R. L.

1 Grochocka L.

1 Szymanski J.

1 Tepper B.

1 Winnicka M.

1 Winnicka M. M.

1 2019

1 2014

2 2013

The role of interleukin 6 in stress response and anxiety-driven behavior in mice

Interleukin 6 deficiency affects spontaneous activity of mice in age- and sex-dependent manner

The role of interleukin 6 in behavior of aged mice

Adult neurogenesis in opossums and hippocampal-dependent learning