Peripheral administration of group III mGlu receptor agonist ACPT-I exerts potential antipsychotic effects in rodents.

Several lines of evidence implicate dysfunction of glutamatergic neurotransmission in the pathophysiology of schizophrenia. Previous behavioral studies have indicated that metabotropic glutamate (mGlu) receptors may be useful targets for the treatment of psychosis. It has been shown that agonists and positive allosteric modulators of group II mGlu receptors produce potential antipsychotic effects in behavioral models of schizophrenia in rodents. Group III mGlu receptors seem to be also promising targets for a variety of neuropsychiatric and neurodegenerative disorders. However, despite encouraging data in animal models, most ligands of group III mGlu receptors still suffer from weak affinities, incapacity to cross the blood-brain barrier or absence of full pharmacological characterization. These limitations slow down the validation process of group III mGlu receptors as therapeutic targets. In this work, we choose to study an agonist of group III mGlu receptors (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-I) using intraperitoneal administration in three animal behavioral models predictive of psychosis or hallucinations. The results of the present study show that ACPT-I, given at doses of 10 or 30mg/kg, decreased MK-801-induced hyperlocomotion and at a dose of 100mg/kg decreased amphetamine-induced hyperlocomotion in rats. Furthermore, ACPT-I dose-dependently decreased DOI-induced head twitches in mice and suppresses DOI-induced frequency and amplitude of spontaneous EPSPs in slices from mouse brain frontal cortices. These data demonstrate that ACPT-I is a brain-penetrating compound and illustrates its promising therapeutic role for the treatment of schizophrenia.

Interleukin-2 receptor positive cells in human decidua during the first trimester of pregnancy and their association with macrophages.

Maternal immune rejection of the fetus could sometimes be the cause of unexplained recurrent spontaneous abortion. Components of the T cell-mediated immunity were investigated in the first trimester of pregnancy in women having spontaneous abortion and compared to those with normal pregnancy having a termination on social grounds. Interleukin 2 (IL-2) had no proliferative effect on the trophoblasts of chorionic villi and there were also no IL-2 receptors in these cells. However IL-2 receptor positive cells were found in the decidua in 7 out of 24 women with normal pregnancy and in 12 out of 18 with spontaneous abortion. A high density of macrophages showed an association with IL-2 receptors in both groups. There were no differences with respect to T-cytotoxic cells and T-helper cells in cases of normal pregnancy (with and without IL-2 receptor positive cells), whereas in women having spontaneous abortion we found lower densities of T-helper and T-cytotoxic cells in those without IL-2 receptors than in those with IL-2 receptors.

Demonstration of the ability of Hofbauer cells to phagocytose exogenous antibodies.

We have studied the effects of the anti-human chorionic gonadotropin and anti-human antithrombin III antibodies on Hofbauer cells from human immature placenta, when applied to either intact villi or on cell culture. Trypsin treatment of the villi results in a mixed cell culture mainly composed of isolated Hofbauer cells but which also contains a variable number of mesenchymal cells and a few syncytiotrophoblastic cells. In all samples analysed only 7-8% of the Hofbauer cells and some syncytiotrophoblastic cells exhibited a macrophagic activity 24 h after incubation of the cultures with the antisera. That only certain proportions of Hofbauer and syncytiotrophoblastic cells express macrophagic activity is also seen when intact villi are incubated for 24 h with these antibodies. Indeed, neither all the villi nor all these cells within a single villus are positively stained. The fact that only a fraction of Hofbauer cells and syncytiotrophoblast express a macrophagic activity may suggest that only some cells, amongst both these cell types, are involved in the protection of the fetus against maternal immunological rejection by removing immunological complexes.

Inhibition of fibroblast proliferation in a culture of human endometrial stromal cells using a medium containing D-valine.

A nutrient medium in which D-valine was substituted for L-valine inhibited fibroblast proliferation in a culture of human endometrial stromal cells. Fibroblasts were not killed by D-valine and were able to grow again when D-valine was replaced by L-valine. The stromal cells proliferate in the D-valine medium only when seeded at high density. They were distinguished from fibroblasts by their morphology in light microscopy, their surface characteristics at scanning electron microscopy and their lower staining with fibronectin antibodies.

Identification of human chorionic gonadotropin (HCG) secreting cells and other cell types using antibody to HCG and a new monoclonal antibody (mABlu-5) in cultures of human placental villi.

We have identified cells which secrete human chorionic gonadotropin (HCG) of cultures if first trimester placental villi. As a first step, we identified epithelial cells using a new monoclonal antibody. We then added HCG antibodies to the cultured cells. We found that syncytiotrophoblast (and not cytotrophoblast), Hofbauer cells and some mesenchymal cells stained with HCG antibodies.

Immunocytochemical identification of mitotic Hofbauer cells in cultures of first trimester human placental villi.

In cultures of first trimester human placental villi, mitotic Hofbauer cells have been identified using a combined autoradiographic and immunostaining technique for the demonstration of HCG, a marker for Hofbauer cells.