Time-dependent effects of striatal interleukin-2 on open field behaviour in rats

Karrenbauer, B.D.; Ho, Ying-Jui; Ludwig, Verena; Löhn, Jeanette; Spanagel, Rainer; Schwarting, Rainer K.W.; Pawlak, Cornelius R.

doi:10.1016/j.jneuroim.2008.12.003

Cited by 14 publications

(10 citation statements)

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“…IL-2 is synthesized centrally, where it is distributed throughout the CNS. In addition, increased c-Fos expression (suggesting increased metabolic activity) in these forebrain neurons following stereotypic behavior overlap extensively with soluble IL-2 receptor labeling in the same regions of forebrain, which suggest that these areas are associated with several of the behavioral motor processes examined in the present study [15], [24], [40]–[42].…”

Section: Discussionsupporting

confidence: 55%

“…There is a positive relationship between rearing behavior, IL-2 [14], [24] and dopamine in the ventral striatum [25], which is of interest because of its relationship between motor functions and goal-seeking/motivational responses, in addition to the fact that this region of the forebrain projects to other areas involved in motor and tic disturbances [3], [15]. Therefore, it is possible that dopamine’s effects upon both motor and emotional processes are mediated in part through a cytokine mechanism.…”

Section: Discussionmentioning

confidence: 98%

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Short- and Long-Term Effects of Interleukin-2 Treatment on the Sensitivity of Periadolescent Female Mice to Interleukin-2 and Dopamine Uptake Inhibitor

et al. 2013

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Interleukin (IL)-2, a T-helper 1 (Th1) cell-derived cytokine, which potently modulates dopamine activity and neuronal excitability in mesolimbic structures, is linked with pathological outcomes (e.g., schizophrenia, depression, etc.) that at least partly reflect alterations in central dopaminergic processes. It has been suggested that dopamine neurons undergo pruning during adolescence and abnormalities in pruning predispose individuals to behavioral disorders. Since IL-2 is known as a neurodevelopmental factor affecting associated behavioral processes, the present study tested whether IL-2 can modulate stereotypic behaviors in both the periadolescent and adult periods. This study determined whether IL-2 treatment would produce long-lasting changes in sensitivity to a later challenge with IL-2 or GBR 12909, a highly selective dopamine uptake inhibitor. Four experiments were conducted. Firstly, a decrease in novelty-induced stereotypic behavior was observed in BALB/c periadolescent mice (38 days of age) following IL-2 administration (0.4 µg/2 ml) relative to vehicle control. In the second experiment, an initial dose of IL-2 was given in the periadolescent period, but did not affect rearing responses. A second dose of IL-2 given to the animals 30 days later as adults, resulted in a significant increase in rearing behaviors relative to control animals. In the third experiment, separate groups of experimental and control mice were administered GBR 12909, a highly selective dopamine reuptake inhibitor, 30 days following treatment with either IL-2 or vehicle. It was noted that this experimental group, which initially received IL-2, exhibited stereotypy, as evidenced by increased sniffing behavior. A fourth experiment revealed that IL-2 administered in periadolesecence and adulthood had no effect on other motor responses, indicating that IL-2 selectively modulates selective stereotypic behaviors. The results provide evidence, for the first time, that long-term changes in stereotypy in periadolescent mice are linked to an IL-2 mechanism, possibly utilizing dopamine.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 98%

Short- and Long-Term Effects of Interleukin-2 Treatment on the Sensitivity of Periadolescent Female Mice to Interleukin-2 and Dopamine Uptake Inhibitor

et al. 2013

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“…The open-field test was performed under light condition as described earlier [15] . The open field consisted of a square wooden platform (45 × 45 cm) with sidewalls (20cm height), inner walls and floor painted white.…”

Section: Neurobehavioral Analyses Open Field Testmentioning

confidence: 99%

Biochemical and Behavioral Evidences for Neuromodulatory Properties of Selaginella prophyalxis Against 3-Nitropropionic Acid in Mice

Chandran

Muralidhara

2016

International Journal of Neurology Research

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AIM: Experimental evidence on the neuromodulatory properties of the Indian resurrection herb 'Selaginella' (a pteridophyte) is limited. Here, we examined the hypothesis that extract of Selaginella delicatula can render protection against 3-nitropropionic acid (3NP)induced oxidative impairments and neurotoxicity. MATERIALS AND METHODS: Mice provided with supplements S. delicatula aqueous extracts (SDAE) orally (400 mg/kg bw/d, 15d) were challenged with 3NP (50 mg/kg bw/d, i.p. from day 11-day 15). RESULTS: Exposure to 3NP induced significant motor deficits, as evidenced by the reduced stride length, increased narrow beam latency and overt behavioral deficits in the open field apparatus. Interestingly, there was a significant delay in the onset and the intensity of neurobehavioral deficits among SDAE prophylactic mice. Biochemical investigation of striatum revealed that SDAE prophylaxis modulated the striatal redox status but also attenuated the 3NP-induced oxidative stress, activity of antioxidant enzymes and mitochondrial complex II. More importantly, AChE activity and dopamine levels were nearly normal among SDAE-mice. CONCLUSION: Collectively, these data suggest that neuroprotection rendered by SDAE prophylaxis may be primarily attributed to the restoration effect on antioxidant defence and mitochondrial function which lead to improved locomotor phenotype. We propose that Selaginella aqueous extracts may provide new perspectives for the development of therapeutic strategies in protecting the brain against oxidative stress-mediated neurodegenerative disorders. , the major contribution factors for the pathophysiology of the disease include excitotoxicity, dopamine toxicity, mitochondrial dysfunction, oxidative stress, apoptosis and autophagy. The process of neurodegeneration can be mimicked in vitro/ in vivo by exposure to various toxins viz., Rotenone, 3-nitro propionic acid (3NP), Paraquat, MPTP, MPP+M 6-OHDA etc [3][4][5] .3NP, a mycotoxin is known to cause significant neurotoxicity predominantly affecting the neurons involved in locomotor behavior in humans and animals. Studies in laboratory animals, suggest that 3NP induces neuronal damage that mainly affects the striatum and mimics most of the histological and neurochemical features of HD [4,6] and hence this phenotypic model is gaining attention as a valuable tool to develop new therapies for HD [4] . The mechanism of 3NP induced neurotoxicity involves inhibition of succinate dehydrogenase (SDH), an enzyme that acts in mitochondrial tricarboxylic acid cycle and the electron transport chain at complex II [7] along with increased oxidative stress, as demonstrated by recent studies leaving scope for use of phytochemicals to reverse the neuronal damage.Although the treatment approaches are limited [1,2] , proposed treatment paradigms generally involve the use of natural antioxidants exhibiting their action by either or combination of speculated processes involving (i) suppression of oxidative/ nitrosative stress (ii) enhancement of mitochondrial function in br...

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“…Microinjection of IL2 into the striatum produces time- and dose-dependent effects. A higher dose of IL2 (25 ng) is anxiolytic whereas a lower dose (1 ng) is anxiogenic ( Pawlak and Schwarting, 2006; Karrenbauer et al ., 2009)). Lastly, a paradoxical effect of IL1β has also been shown.…”

Section: Introductionmentioning

confidence: 99%

Essential role of interleukin-15 receptor in normal anxiety behavior

Hsuchou

et al. 2010

Brain, Behavior, and Immunity

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The interactions between the cytokine interleukin (IL)-15 and the classical neurotransmitter GABA have been shown in IL15Rα receptor knockout mice by observations of memory deficits and reduction of GABA. To test the hypothesis that IL15 affects anxiety-like behavior, knockout mice without IL15, IL15Rα, or the co-receptor IL2Rγ were subjected to open-field and elevated plus maze tests. All three strains showed reduction of anxiety, with greater changes in the IL15Rα knockout mice than in the IL15 or IL2Rγ knockout mice. This unexpected observation is opposite to the reported increase of anxiety in mice lacking other proinflammatory cytokines or their receptors. The reduced anxiety was not associated with changes in associated serum cytokines. However, western blotting, qPCR, and immunohistochemistry all showed that IL15Rα knockout mice had mild microgliosis and astrogliosis in the hippocampus. To determine whether this gliosis plays a role in decreasing anxiety, IL15Rα knockout mice were treated with minocycline, but this did not cause a change in open field performance. To determine whether IL15 plays a direct role in anxiety, wildtype mice were treated with IL15 by intraperitoneal injection. This also failed to cause a change in open field behavior under the experimental conditions tested. Thus, IL15Rα is essential for normal anxietylike behavior, but inhibition of gliosis in the fearless IL15Rα knockout mice or IL15 treatment of normal mice did not acutely modulate behavioral performance as tested.

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Time-dependent effects of striatal interleukin-2 on open field behaviour in rats

Cited by 14 publications

References 60 publications

Short- and Long-Term Effects of Interleukin-2 Treatment on the Sensitivity of Periadolescent Female Mice to Interleukin-2 and Dopamine Uptake Inhibitor

Short- and Long-Term Effects of Interleukin-2 Treatment on the Sensitivity of Periadolescent Female Mice to Interleukin-2 and Dopamine Uptake Inhibitor

Biochemical and Behavioral Evidences for Neuromodulatory Properties of Selaginella prophyalxis Against 3-Nitropropionic Acid in Mice

Essential role of interleukin-15 receptor in normal anxiety behavior

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