Differences in Mouse Maternal Care Behavior – Is There a Genetic Impact of the Glucocorticoid Receptor?

Depressive episodes are frequently preceded by stressful life events. Evidence from genetic association studies suggests a role for the glucocorticoid receptor (GR), an essential element in the regulation of stress responses, in the pathophysiology of the disorder. Since the stress response system is affected by pregnancy and postpartum-associated changes, it has also been implicated in the pathophysiology of postpartum depression. Using a 2×2 factorial design, we investigated whether a heterozygous deletion of GR would influence maternal care behavior in C57BL/6 and Balb/c mice, two inbred strains known to display qualitative differences in this behavior. Behavioral observation was carried out between postnatal days 1 and 7, followed by a pup retrieval test on postnatal days 7 or 8. While previously noted inter-strain differences were confirmed for different manifestations of caring behavior, self-maintenance and neglecting behaviors as well as the pup retrieval test, no strain-independent effect of the GR mutation was noted. However, an interaction between GR genotype and licking/grooming behavior was observed: it was down-regulated in heterozygous C57BL/6 mice to the level recorded for Balb/c mice. Home cage observation poses minimal disturbance of the dam and her litter as compared to more invasive assessments of dams' emotional behavior. This might be a reason for the absence of any overall effects of the GR mutation, particularly since GR heterozygous animals display a depressive-like phenotype under stressful conditions only. Still, the subtle effect we observed may point towards a role of GR in postpartum affective disorders

Impaired B cell responses to orally administered antigens in lamina propria but not Peyer's patches of Gαi2-deficient mice prior to colitis

Despite numerous studies on the intestinal immune system in patients with inflammatory bowel disease (IBD) and animal models of IBD, very little is known about the immune reactivity of mucosal lymphocytes following oral immunizations under these circumstances. The reactivity of Peyer's patch (PP) and lamina propria (LP) T and B lymphocytes in inhibitory G-protein α2 subunit-deficient (Gαi2(–/–)) mice developing an IBD resembling ulcerative colitis was investigated following repeated oral immunizations with keyhole limpet haemocyanin (KLH), together with the adjuvant cholera toxin, prior to colitis. The antigen-specific B-cell response in the LP of both the small and the large intestines was significantly reduced in Gαi2(–/–) as compared to wild-type mice. In contrast, the frequency of KLH-specific immunoglobulin (Ig)-producing cells in the PP did not differ between Gαi2(–/–) and wild-type mice, whereas the total frequency of Ig-producing cells as well as the frequency of enteric flora-specific Ig-producing cells in the PP was significantly increased in Gαi2(–/–) as compared to wild-type mice. Analysis of T cell responses following restimulation ex vivo with KLH revealed a dramatic increase in the production of interferon-γ in mesenteric lymph node, PP and LP lymphocytes from Gαi2-deficient as compared to wild-type mice, together with decreased production of interleukin-10 in all locations except the PP

Effects of Prostaglandin E1 analogue, Misoprostol, on the development of adjuvant arthritis in rats

Prostaglandins (PG) E , E and the PGE analogue, misoprostol, have been shown to inhibit T-cell functions and the production by activated monocytes or macrophages of interleukin-1, indicating that these PGs may have potential anti-arthritic activity by suppressing T-cell and monocyte activity. In view of this the potential anti-arthritic effects of the long half-life PG, misoprostol (MPL), were examined in adjuvant arthritic rats under prophylactic and therapeutic treatment regimes. Transcutaneous or subcutaneous MPL given at 200 Μg/kg/day but not at 50 or 5 Μg/kg/day when given 0 to +5 or 0 to + 14 days post-induction inhibited the development of the disease whereas the orally administered drug was without effects. MPL given transcutaneously with oral indomethacin (1 or 2 mg/kg/day) on days +17 to + 30 post-induction produced greater anti-inflammatory effects than with this NSAID alone. MPL given orally in combination with this NSAID did not enhance the anti-inflammatory effects of the latter. MPL 200 Μg/kg given transcutaneously exhibited anti-ulcer activity against indomethacin (30 mg/kg p.o.), naproxen (10 mg/kg i.p.) or piroxicam (5 mg/kg i.p.) induced gastric damage in arthritic rats and this was comparable with that from 100 Μg/kg MPL given orally. These results show that MPL has both unique anti-arthritic effects only when given transcutaneously or parenterally as well as anti-ulcer activity.K. D. Rainsford, M. W. Whitehouse and B. Vernon-Robert