Behaviour of small inhibitory interneurons in early postnatal mouse cerebellar microexplant cultures: a video time-lapse analysis.

The aim of this work was to investigate how the environment of the neuropil determines the positioning and differentiation of neurons that are postsynaptic to them. We investigated how stellate and basket cells, the small inhibitory interneurons of the cerebellar cortex, find their perpendicular orientation to the direction of fasciculated granule cell axons. Cultures of early postnatal mouse cerebellar microexplants showing this cellular behaviour in vitro were analysed by video time-lapse cinematography and evaluated by morphometry. The small interneurons were first detectable when they migrated, intermingled with granule cells, away from the explant along the radial fascicles of granule cell neurites. During migration some cells suddenly changed their orientation by extending neurites in perpendicular orientation to the radial fascicles. These cells were all GABA-immunoreactive and expressed the cytoskeletal markers tau in the thin axon-like process and MAP2 in the thicker dendrite-like arborizations at the opposite pole of the cell body. After having translocated in perpendicular orientation, these neurons were again able to turn back to move along the radial neurite bundles to another position. Furthermore, while in perpendicular orientation, the processes of these cells repelled each other upon contact of their growth cones, leading to equal spacing between the cell bodies with time in culture.

Thymic factor-induced reduction of pulmonary metastases in mice with FSA-1 fibrosarcoma.

The biological activities of two thymic factors, serum thymic factor thymulin normally present in serum and thymosin alpha-1 (Ta-1) extracted from the thymus gland, have been studied. The effects of the factors on the growth of pulmonary metastases and survival of mice were evaluated in pathogen-free C3H/fSed males. Mice were injected i.v. with the single cell suspension of the syngeneic methylcholanthrene-induced fibrosarcoma. The treatment with thymulin and Ta-1 started two days after injection of 5 x 10(4) to 2 x 10(5) tumor cells per mouse. Different doses of the thymic factors were administered S.C. in sets of 5 daily injections through a period of 2 or 3 weeks. Numbers of tumor colonies in the lung were determined two weeks after the cell injection. Treatment with 0.1 micrograms Ta-1 per injection through the period of two or three weeks, prolonged the survival of tumor-injected mice. Similar effects were observed in mice treated with 0.01 microgram thymulin per injection. Numbers of tumor colonies in lungs of these mice two weeks after the cell injection were also reduced in comparison with saline-treated controls. These findings correlated with prolonged survival time of identically treated mice. The effectiveness of thymic factors in reducing tumor growth was dependent on the tumour load. In addition, the effects induced by Ta-1 persisted longer than observed in thymulin-treated mice. Mice challenged 150 days after the primary tumor cell injection and treatment with Ta-1 demonstrated increased resistance to tumor, while mice treated with other factors behaved as saline-treated controls. The results indicate that both factors exert beneficial effects against tumor growth, although mode of action for each factor may be different.