Lyophilized aspirin with trehalose may decrease the incidence of gastric injuries in healthy dogs.

Trehalose has several novel anti-inflammatory and cell-protective functions. We hypothesized that lyophilized aspirin/trehalose could decrease the severity of aspirin-induced gastropathy. Thirteen dogs were assigned into aspirin, lyophilized aspirin/trehalose, and control groups, and the gastric lesions were assessed on gastroscopy with the modified Lanza scale. Another 6 dogs were used to measure the plasma aspirin concentration by high-performance liquid chromatography after aspirin or lyophilized aspirin/trehalose administration. The results indicated that lyophilized aspirin/trehalose induced less gastric ulceration than aspirin despite maintaining therapeutic concentrations of plasma aspirin in both the groups. Lyophilized aspirin/trehalose might be a solution to decrease aspirin-induced gastropathy.

Roles of progranulin in sexual differentiation of the developing brain and adult neurogenesis.

Progranulin (PGRN) is a growth modulating factor released by a variety of cells. This molecule has gained the attention of the neuroscience community with recent discoveries of multifunctional roles of PGRN in normal brain and neurodegenerative disorders. We focus on novel roles of PGRN as a sex steroid-responsible gene in the developing and adult rodent brain. While the developing brain is feminine by default, hormone exposure, including androgen and estrogen, induces masculinization during the critical period. We have shown that PGRN is a sex steroid-responsible gene that may be involved in masculinization of the perinatal rat brain. We also found that in adult rats PGRN gene expression was up-regulated by estrogen in the hippocampus, suggesting that PGRN may mediate the mitogenic effects of estrogen in the active area of neurogenesis. Since it has been recently reported that mutations in PGRN gene are responsible for a type of frontotemporal lobar degeneration in humans, PGRN appears to be also involved in modulating neurodegeneration. Together, PGRN gene expression is induced by estrogen in both developing and adult brains, and it may play multifunctional roles in the organization of functional masculinization in the developing brain and the maintenance of adult brain function.

Alteration of behavioural phenotype in mice by targeted disruption of the progranulin gene.

Sexual differentiation of the brain in rodents is achieved by estrogens, which are converted from androgens in the brain, during the perinatal period. We have identified the progranulin (PGRN) gene as one of the sex steroid-inducible genes that may be involved in masculinization of the rat brain. In the present study, we generated a line of mice with targeted disruption of the PGRN gene, and investigated male sexual behaviour, aggression and anxiety. PGRN-deficient mice exhibited a decrease in ejaculation incidence, while the latency and frequency of both mount and intromission were unchanged. For the aggressive behaviour test, the resident-intruder paradigm was used, and PGRN-deficient mice exhibited enhanced aggressiveness. In wild-type mice, males exhibited lower levels of anxiety than females by the open field test, while male PGRN-deficient mice exhibited an elevated level of anxiety and sex difference in anxiety was not observed. In addition, mRNA expression of the serotonergic receptor 5-HT1A, which could be related to the inhibition of aggression and anxiety, was significantly reduced in the hippocampus of PGRN-deficient mice after aggressive encounters. On the other hand, deficiency of the PGRN gene did not affect serum testosterone concentrations. These results suggest that PGRN gene plays a role in establishing sexual dimorphic behaviours at least partially by modulating the brain serotonergic system.

Maintenance of gonadotropin secretion by glucocorticoids under stress conditions through the inhibition of prostaglandin synthesis in the brain.

We have previously reported that glucocorticoids counteract the suppressive effects of tumor necrosis factor-alpha on both pulsatile and surge secretion of LH. This suggests that glucocorticoids have a protective effect on reproductive function under infectious stress. In the present study, we examined whether glucocorticoids maintain pulsatile LH secretion under various conditions of acute stress and the possible involvement of prostaglandins (PGs) in glucocorticoid actions. Three different types of stressors, namely infectious (lipopolysaccharide, 0.5 microg/kg), hypoglycemic (2-deoxy-D-glucose, 100 mg/kg), and restraint stress (1 h) were applied to ovariectomized rats. In ovariectomized rats, LH pulses were partially suppressed by restraint, but not by lipopolysaccharide or 2-deoxy-D-glucose. On the other hand, adrenalectomy (ADX) significantly enhanced the suppressive effects of all the stressors applied on LH pulses. Treatment with both corticosterone (25 mg/kg) and indomethacin (10 mg/kg) in ADX rats significantly attenuated the suppressive effects of these stressors on LH pulses. In addition, the immunoreactivity of cyclooxygenase-2, a PG-synthesizing enzyme, in the brain under stress conditions was much enhanced by ADX, and this was counteracted by corticosterone treatment. Similarly, an increase in body temperature under restraint stress was enhanced by ADX and suppressed by corticosterone. These results suggest that suppression of LH pulsatility by stress is mediated by PGs in the brain, and that increased release of endogenous glucocorticoids in response to stress counteracts this suppression by inhibiting PG synthesis, and thereby maintains reproductive function regardless of the nature of the stressor.