TY  - JOUR
A1  - Üçeyler, Nurcan
A1  - Topuzoğlu, Tengü
A1  - Schießer, Peter
A1  - Hahnenkamp, Saskia
A1  - Sommer, Claudia
T1  - IL-4 Deficiency Is Associated with Mechanical Hypersensitivity in Mice
JF  - PLoS One
N2  - Interleukin-4 (IL-4) is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko) mice to characterize their pain behavior before and after chronic constriction injury (CCI) of the sciatic nerve as a model for neuropathic pain. We investigated opioid responsivity and measured cytokine and opioid receptor gene expression in the peripheral and central nervous system (PNS, CNS) of IL-4 ko mice in comparison with wildtype (wt) mice. Naïve IL-4 ko mice displayed tactile allodynia (wt: 0.45 g; ko: 0.18 g; p<0.001), while responses to heat and cold stimuli and to muscle pressure were not different. No compensatory changes in the gene expression of tumor necrosis factor-alpha (TNF), IL-1β, IL-10, and IL-13 were found in the PNS and CNS of naïve IL-4 ko mice. However, IL-1β gene expression was stronger in the sciatic nerve of IL-4 ko mice (p<0.001) 28 days after CCI and only IL-4 ko mice had elevated IL-10 gene expression (p = 0.014). Remarkably, CCI induced TNF (p<0.01), IL-1β (p<0.05), IL-10 (p<0.05), and IL-13 (p<0.001) gene expression exclusively in the ipsilateral spinal cord of IL-4 ko mice. The compensatory overexpression of the anti-inflammatory and analgesic cytokines IL-10 and IL-13 in the spinal cord of IL-4 ko mice may explain the lack of genotype differences for pain behavior after CCI. Additionally, CCI induced gene expression of μ, κ, and δ opioid receptors in the contralateral cortex and thalamus of IL-4 ko mice, paralleled by fast onset of morphine analgesia, but not in wt mice. We conclude that a lack of IL-4 leads to mechanical sensitivity; the compensatory hyperexpression of analgesic cytokines and opioid receptors after CCI, in turn, protects IL-4 ko mice from enhanced pain behavior after nerve lesion.
KW  - mouse models
KW  - animal behavior
KW  - sciatic nerves
KW  - spinal cord
KW  - opioids
KW  - cytokines
KW  - gene expression
KW  - mice
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137924
VL  - 6
IS  - 12
ER  - 
TY  - JOUR
A1  - Hofmann, Lukas
A1  - Karl, Franziska
A1  - Sommer, Claudia
A1  - Üçeyler, Nurcan
T1  - Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease
JF  - PLoS ONE
N2  - Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3) due to α-galactosidase A (α-Gal A) deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO) and compared results with those of age-matched male wildtype (WT) littermates. Young (3 months) and old (≥ 18 months) mice were tested in the naïve state and after i.pl. injection of complete Freund`s adjuvant (CFA) as an inflammatory pain model. We used the elevated plus maze (EPM), the light-dark box (LDB) and the open field test (OF) to investigate anxiety-like behavior. The forced swim test (FST) and Morris water maze (MWM) were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in naïve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05). After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05) and naïve young Fabry KO mice (p<0.05) in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05). Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors.
KW  - cognitive impairment
KW  - mouse models
KW  - depression
KW  - swimming
KW  - learning
KW  - Fabry disease
KW  - genetics
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170745
VL  - 12
IS  - 6
ER  -