Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2000-04-17
2001-10-30
Reamer, James H. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
Reexamination Certificate
active
06310097
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an agent for protecting central nerve cells and enhancing survival thereof
BACKGROUND ART
Hippocampal neurons have widely been used in the field of the neurophysiology as central nerve cells that can be cultured in laboratories. It has been known that a significant number of the neurons die in one week from the start of the culture when the cells are primarily cultured alone. As a method for long-term culture of hippocampal neurons, co-culture of the cells with glial cells (gliacytes that fill spaces between neurons and their neurites) is known. However, since the culture system is not a monoculture system, it is not suitable for researches on auxotrophy of hippocampal neurons alone, neuronal responses to polypeptide neurotrophic factors and the like. As a method for culturing hippocampal neurons in the absence of glial cells, a method is known wherein the neurons are cultured in the presence of all non-essential amino acids. However, survival time of the cells and number of survived cells are significantly lower than those attained by the co-culture with glial cells.
In primary culture system of hippocampal neurons, it has also been known that long term survival of neurons can be achieved by the addition of culture supernatant of glial cells (astrocyte conditioned medium, ACM). A method for such culture has been established by Goslin et al. (Goslin, K. and Banker, G., “Culturing Nerve Cells”, Ed. by Banker, G. et al., p.251-278, The MIP Press, England). However, it has not been revealed which substance in the culture supernatant enhances survival of the neurons.
It has also been known that L-serine acts as an important factor for morphodifferentiation of fowl ganglions which are peripheral nerve cells (Savoca, R., Ziegler, U. and Sonderegger, P., Journal of Neuroscience Methods, 61, pp.159-167, 1995). However, the action of L-serine disclosed in the publication is mainly focused on the morphogenesis of neurons, and the publication neither teaches nor suggests whether L-serine may have any action on the survival of neurons. Moreover, the cells used in the experimental system were peripheral nerve cells, which are totally different from central nerve cells such as hippocampal neurons in generation and functions. Therefore, action of L-serine on central nerve cells is not taught by the publication
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide a substance that enhances survival of neurons. Another object of the present invention is to provide an agent for improving cerebral functions.
The inventors of the present invention eagerly conducted researches to achieve the foregoing objects. As a result, they found that glial cells secreted a cell survival-enhancing substance for hippocampal neurons, and the substance was not produced by the hippocampal neurons. They also found that the substance was L-serine. Moreover, the inventors of the present invention also found that L-serine or glycine had cell survival-enhancing action on central nerve cells such as cerebellar granule and Purkinje cells, as well as on hippocampal neurons. The present invention was achieved on the basis of these findings.
The present invention thus provides an agent for enhancing cell survival of central nerve cells, which comprises as an active ingredient a substance selected from the group consisting of L-serine, glycine, and fatty acid compounds thereof, preferably L-serine and/or glycine, more preferably L-serine. According to a preferred embodiment of the present invention, there is provided an agent for enhancing cell survival of central nerve cells which comprises L-serine as an active ingredient.
As another aspect of the present invention, there is provided a medicament for preventive and/or therapeutic treatment of cerebral dysfunction which comprises as an active ingredient a substance selected from the group consisting of L-serine, glycine, and fatty acid compounds thereof, preferably L-serine and/or glycine, more preferably L-serine. As other aspects of the present invention, there are provided use of a substance selected from the group consisting of L-serine, glycine, and fatty acid compounds thereof, preferably L-serine and/or glycine, more preferably L-serine, for manufacture of the aforementioned medicament for preventive and/or therapeutic treatment, and a method for preventive and/or therapeutic treatment of cerebral dysfunction which comprises the step of administering to a patient a preventively and/or therapeutically effective amount of a substance selected from the group consisting of L-serine, glycine, and fatty acid compounds thereof, preferably L-serine and/or glycine, more preferably L-serine.
As a further aspect of the present invention, there is provided a medium composition for culture of central nerve cells which contains L-serine or glycine as at agent for enhancing cell survival of central nerve cells.
REFERENCES:
patent: 5728728 (1998-03-01), Kozachuk
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Furuya Shigeki
Hirabayashi Yoshio
Mitoma Jyunya
Greenblum & Bernstein P.L.C.
Reamer James H.
Riken
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