|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1996 : ¥1,100,000 (Direct Cost : ¥1,100,000)
It is well known that the leptomeninges (pia and choroid plexus) covering the brain surface take a part of the blood/CSF barrier. In addition to such function, several previous findings may rise the possibility that the tissue is involved in the regulation or maturation of the brain. In order to solve this, we performed following experiments.
1, We have prepared cultures of leptomeningeal cells from newborn rats, and collected the medium conditioned with such cells. Analysis of the protein constitute of the medium revealed that many biologically-active proteins were secreted from the cultivated leptomeningeal cells. They included beta-trace protein (prostaglandin-D-synthase), IGF-1/IGFBP-2, transferrin, apolipoprotein E,cystatin C,beta 2 microglobulin, SPARC,cyclophilin C,extracellular superoxide dismutase, ubiquitin, lysozyme C,cadherin-11 and follistatin-related protein. This protein spectrum suggests that the leptomeningeal cells secrete biologically-important (neurotrophic factors a
nd scavengers of wasted materials) protein factors into CSF in vivo.
2.Next, we examined if such proteins were involved in the degeneration processes of neurons after ischemia and target deprivation. After ischemia, the accumulation of apolipoprotein E,transferrin and cystatin C occurred in the degenerating neurons in CA 1 areas. beta-2-Microglobulin appeared in the cell bodies of vasopressin neurons after hypophysectomy. Cystatin C and apolipoprotein E also accumulated in such degenerating neurons, but not transferrin in the hypophysectomized rats. These findings may supports further the hypothesis that the leptomeninges plays a scavenging role in the brain.
Finally, we have established a sensitive assay system for beta-trace protein, the major product of the leptomeningeal cells. Using this we found that there was a developmental change in the protein levels in CSF.A peripheral administration of retinoic acid caused a significant drop in its CSF Ievels suggesting the presence of a regulatory pathway through vitamin A metabolism.
In summary, the present findings suggest that the leptomeninges play important roles such as neurotrophic support and scavenger in the brain. Less