Corticotropin-releasing factor (CRF) and urocortin promote the survival of cultured cerebellar GABAergic neurons through the type 1 CRF receptor.

Corticotropin releasing factor (CRF) is known to be involved in the stress response and in some degenerative brain disorders. In addition, CRF has a role as a neuromodulator in adult cerebellar circuits. Data from developmental studies suggest a putative role for CRF as a trophic factor during cerebellar development. In this study, we investigated the trophic role for CRF family of peptides by culturing cerebellar neurons in the presence of CRF, urocortin or urocortin II. Primary cell cultures of cerebella from embryonic day 18 mice were established, and cells were treated for either 1, 5 or 9 days with Basal Medium Eagles complete medium alone or complete medium with 1 microM CRF, urocortin, or urocortin II. The number of GABA-positive neurons in each treatment condition was counted at each culture age for monitoring the changes in neuronal survival. Treatment with 1 microM CRF or 1 microM urocortin increased the survival of GABAergic neurons at 6 days in vitro and 10 days in vitro, and this survival promoting effect was abolished by treatment with astressin in the presence of those peptides. Based on these data, we suggest that CRF or urocortin has a trophic role promoting the survival of cerebellar GABAergic neurons in cultures.

Immunocytochemical study on the distribution of c-myb in the central nervous system of the transgenic mice expressing a human copper/zinc superoxide dismutase mutation.

Although our previous study showed the constitutive expression of c-myb in neurons, suggesting that this gene might be involved in the normal function of these cells, there were no reports on the expression pattern of c-myb under pathological conditions. In the present study, we first investigated the changes in c-myb immunoreactivities (IRs) in the central nervous system of the transgenic mice expressing a human copper/zinc superoxide dismutase (Cu/Zn SOD) mutation. The distribution of c-myb was enhanced in the various brain regions of transgenic mice expressing a mutated human Cu/Zn SOD gene. Immunohistochemistry showed intensely stained c-myb IR glial cells with the appearance of astrocytes within the various brain regions of transgenic mice such as the gray matter of the midbrain, medulla oblongata and spinal cord. Even though the exact functions of c-myb in the normal and pathological states were not clearly revealed until now, we think that the increase in c-myb expression in the mutant mice could be due to the compensate mechanism of the astrocytes for the reduced defence against superoxide toxicity because the only known function of c-myb was its correlation with the prevention of programmed cell death, which could be deduced from the previous studies.