Effects of water restriction on social behavior and 5-HT neurons density in the dorsal and median raphe nuclei in mice.

We explored here the hypothesis that temporary chronic water restriction in mice affects social behavior, via its action on the density of 5-HT neurons in dorsal and median raphe nuclei (DRN and MRN). For that, we submitted adult C57BL/6 J mice to mild and controlled temporary dehydration, i.e., 6 h of water access every 48 h for 15 days. We investigated their social behavior in a social interaction task known to allow free and reciprocal social contact. Results showed that temporary dehydration increases significantly time spent in social contact and social dominance. It also expands 5-HT neuron density within both DRN and MRN and the behavioral and neuronal plasticity were positively correlated. Our findings suggest that disturbance in 5-HT neurotransmission caused by temporary dehydration stress unbalances choice processes of animals in social context.

Implication of regional brain serotonergic neurons in dorsal and median Raphé nuclei in adaptation to water lacking in Gerbillus tarabuli.

The objective of this work was to investigate the implication of serotonin (5-HT) produced in the dorsal and medial raphé nuclei (DRN and MRN) in water homeostasis in desert animal Gerbillus tarabuli. For that, we measured the density of 5-HT immunolabeled neurons in hydrated and dehydrated animals (over 1 and six months). In this work, 5-HT positive neurons showed some change in shape and colour intensity in dehydrated gerbils comparing with hydrated gerbils. Furthermore a differential increase of 5-HT neurons density was observed in DRN subregions and in MRN following 1 and 6 months of dehydration. This study suggested that neurons in DRN and MRN contain 5-HT in various amounts, thus allowing an adapted response to hydration status. These neurons could mediate one of the adaptation mechanisms of this animal to its desert biotope.

Claudin 3, 4, and 15 expression in solid tumors of lung adenocarcinoma versus malignant pleural mesothelioma.

Epithelioid malignant pleural mesothelioma (MPM) can easily be confused with lung adenocarcinomas (ACAs). In serous effusion, claudin (cldn) 3 is shown to be useful in the diagnosis of mesothelioma vs ACAs. Cldn15 is reported to be overexpressed in epithelioid mesothelioma and absent in human airway epithelium. The aim was to assess the value of cldn3 and cldn4 compared to that of BerEp4 and thyroid transcription factor-1 (TTF1) in differentiating lung ACA from epithelioid MPM and to examine the expression of cldn15 in these tumors. The expression of cldn3, cldn4, cldn15, BerEp4, and TTF1 was examined by immunohistochemistry in a total of 62 human specimen including 28 epithelioid MPMs and 34 ACAs of the lung. In lung ACA, cldn4 was strongly expressed in all 34 (100%) specimens followed by cldn3 in 33 (97%) of 34. BerEp4 was expressed in 32 (94.1%) of 34. TTF1 reacted for only 20 (58.82%) of 34 cases of lung ACA. In MPM specimens, the expression of cldn3 and4 as well as that of TTF1 was completely absent. In contrast, BerEp4 was focally expressed in 5 (17.85%) of 28 cases of epithelioid MPM. Cldn15 was strongly expressed in 53% pf epithelioid MPMs but also in 50% of lung ACAs. Its expression was moderate in normal pleura and limited in normal lung. Cldn3 and cldn4 appear to be the best performing carcinoma markers in discriminating lung ACA from mesothelioma compared with BerEp4 and TTF1. There is no differential expression of cldn15 between the 2 pathologies. However, the limited cldn15 expression in normal tissues and high expression in tumors make it an attractive candidate for cancer therapy.

M14K and M38K malignant pleural mesothelioma cell lines preserve the same claudin-based phenotype in vivo.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with few treatment options. Reliable tumour cell lines for mesothelioma research are rare. Claudins seem to be attractive targets for cancer therapy. AIM: To establish a claudin-based MPM phenotype and to verify whether it is preserved in vitro and in vivo. MATERIALS AND METHODS: Claudin-3 and -4 expression was examined by immunohistochemistry and immunoblotting in MPM (n=15) and lung adenocarcinoma (n=5) specimens. Claudin-3, -4 and -15 expression was also assessed in MPM versus adenocarcinoma cell lines and in MPM versus adenocarcinoma-derived tumour xenografts mouse models. RESULTS: A defined MPM phenotype was established: M14K and M38K cell lines highly express Claudin-15 and calretinin but not claudin-3 nor claudin-4. Similar results were obtained in xenograft mouse models. CONCLUSION: M14K and M38K cell lines, whether in vitro or in an animal model are representative models and appropriate in exploring new therapeutic strategies in MPM that may target claudins.

Adaptation of Camelus dromedarius pars nervosa of the hypophysis to winter and summer living conditions.

The aim of this work is to study the characteristics of the dromedary nervous lobe and determine how the seasons condition its organization. To this end, electron microscopy was performed and examined quantitatively on animals from winter and summer periods. The results show a higher number of cells in the nervous lobe in summer than in winter. The most abundant glial elements in winter are light pituicytes engulfing neurosecretory nerve fibers making neuroglial contact, and dark pituicytes containing numerous heterogeneous light bodies. In summer, the most distinctive glial cells may be pituicytes in a phagocytic state making contact with characteristic large light bodies that could represent a degenerative process of large neuropeptide storage. Granular pituicytes were also observed in contact with glial and neuronal components. However, lipid droplets, described in pituicytes of other mammals, were not observed in our samples. Quantitative analysis of neurovascular contacts revealed that the number of nerve terminals contacting the basal lamina did not differ between summer and winter, but the mean number of glial processes increased in winter. Our data provides evidence that the storage of neuropeptides is very marked in summer and that, associated with an autophagic and phagocytic phenomenon, this suggests an adaptation to anticipate any situation that would cause dehydration of the dromedary. Thus, in its tough environment, the animal remains permanently prepared to avoid any large water loss.

Effect of a water-rich diet on adrenal zona glomerulosa in Gerbillus tarabuli.

The objective of this work is to evaluate the aldosterone level and to study the gerbil adrenal zona glomerulosa morphology in the presence of an important water diet content during seven days. Thirty adult gerbils, Gerbilus tarabuli, were randomly assigned to two watering regimes, with fifteen gerbils per group. The first group was the control and the second group was exposed to a water-rich diet during seven days. Thin sections of the adrenal glands were observed in photonic and electron microscopy. Their blood was sampled and analyzed for aldosterone, electrolyte concentrations and hematocrit. Urine was collected after 24hours. A water-rich diet decreased the body weight but increased the hematocrit, total protein, aldosterone concentration and urine volume. In electronic microscopy, the adrenal zona glomerulosa cells present a decrease in lipid compartment and Golgi apparatus zone development. The blood electrolyte concentrations were not changed significantly. These findings indicate that the water-rich diet exerts a potent stimulatory effect on aldosterone secretion by the gerbil adrenal zona glomerulosa through plasma volume perturbation.