Transgenic overexpression of interleukin-1 receptor antagonist in the CNS influences behaviour, serum corticosterone and brain monoamines.
The effects of brain-directed overexpression of human soluble interleukin-1 receptor antagonist (hsIL-1ra) on behaviour, serum corticosterone (CST) levels and concentrations of dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites in different brain regions, were investigated in six months old homozygotic transgenic male mice (Tg hsIL-1ra(+/+)). The transgenic and age-matched wild type (WT) mice were subjected to a battery of behavioural tests for analysis of open field (OF) behaviours, anxiety in elevated plus maze (EPM), and motor performance in rotarod. One week after the last behavioural test, half of the mice from each genotype were subjected to a mild stress, while the remaining mice served as controls for the determination of serum CST levels and monoamine concentrations in different brain regions. Tg hsIL-1ra(+/+) mice had higher locomotor scores and showed less habituation in the OF test, spent more time in the open arms of the EPM and had similar motor performance as compared to WT mice. The serum CST levels were comparable, both in basal conditions and upon stress, in the two genotypes. Tg hsIL-1ra(+/+) mice had lower concentrations of DA, 5-HT and their metabolites in several brain regions, with different effects on monoamine turnover upon stress. In conclusion, brain-directed overexpression of hsIL-1ra resulted in increased locomotion and decreased habituation, an anxiolytic effect, but did not influence motor performance. Finally, the activation of hypothalamo-pituitary-adrenal (HPA)-axis was comparable in the two genotypes, however Tg hsIL-1ra(+/+) mice had a modified metabolism of brain monoamines as compared to WT mice.
Oprica
Mircea
M
Division of Experimental Geriatrics, Neurotec Department, Karolinska Institutet, Novum, KFC, 4th floor, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden. Mircea.Oprica@neurotec.ki.se
Zhu
Shunwei
S
Goiny
Michel
M
Pham
Therese M
TM
Mohammed
Abdul H
AH
Winblad
Bengt
B
Bartfai
Tamas
T
Schultzberg
Marianne
M
D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood*; D004298:Dopamine / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011597:Psychomotor Performance / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D045442:Rotarod Performance Test; D012701:Serotonin / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013312:Stress, Physiological / Q000378:metabolism
C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D012701:Serotonin; D004298:Dopamine; D003345:Corticosterone