Claims
- 1. A method for preparing a population of mammalian neural cells enriched with neuronal cells comprising the step of exposing a population of neural stem cells comprising neural stem cells with a 5HT1A agonist in an amount and at a frequency of exposure sufficient to induce differentiation of said stem cells to express preferentially the neuronal phenotype.
- 2. The method of claim 1 wherein said mammalian neural stem cells are selected from the group consisting of adult, juvenile, and fetal neural stem cells.
- 3. The method of claim 1 wherein said method is carried out in vitro.
- 4. The method of claim 1 wherein said method is carried out in vivo.
- 5. The method of claim 1 wherein said population of mammalian neural cells comprises at least 90% neural stem cells.
- 6. The method of claim 1 wherein the amount of said 5HT1A agonist is within a range of between about 1 nM and about 1 μM.
- 7. The method of claim 1 wherein said frequency is daily.
- 8. The method of claim 1 wherein said frequency is every other day.
- 9. The method of claim 3 wherein the exposing step comprises adding said 5HT1A agonist to a culture medium and culturing said population in said medium.
- 10. The method of claim 1, wherein the duration of the exposure to said 5HT1A agonist continues for a period of time within the range between about 2 and about 30 days.
- 11. The method of claim 8 wherein the period of time is about 6 days.
- 12. The method of claim 1, wherein the neural stem cells are human neural stem cells.
- 13. The method of claim 12, wherein the human neural stem cells are fetal human neural stem cells.
- 14. The method of claim 1, wherein the mammalian neural stem cells are rat neural stem cells.
- 15. The method of claim 1, wherein the neural stem cells are derived from a primary culture comprising the cortex, cerebellum or striatum neural stem cells.
- 16. The method of claim 1 wherein the 5HT1A agonist is selected from the group consisting of buspirone, serotonin, 5 methoxy N, N dimethyltryptamine, S(-) pindolol, ipsapirone, 3-(2-dimethylaminoethyl)-5-methoxyindole, 1-[3-(3,4-methylene-dioxyphenoxy, 8-Hydroxy-DPAT hydrobromide, (±)-8-Hydroxy-2-dipropylaminotetralin, 8-[4-(1,4-Benzodioxan-2-ylmethylamino)butyl]-8-azaspiro[4.5]decane-7,9-dione, and [(+)-R)-2-cyano-N,N-dipropyl-8-amino-6,7,8,9-tetrahydro-3H-benz[e] indole].
- 17. The method of claim 16, wherein the 5HT1A agonist is buspirone.
- 18. The method of claim 16, wherein the 5HT1A agonist is serotonin.
- 19. The method of claim 17, wherein the amount of buspirone is about 100 nM.
- 20. The method of claim 18, wherein the amount of serotonin is about 5 μM.
- 21. The method of claim 1, further comprising exposing the cell population to Brain-Derived Growth Factor (BDNF).
- 22. The method of claim 21, wherein the amount of BDNF is in a range of about 1 ng/ml to about 50 ng/ml.
- 23. The method of claim 5, wherein the amount of wherein the proportion of said stem cells differentiated into neurons is at least 30%.
- 24. The method of claim 22, wherein the proportion of neurons is 50%.
- 25. A method of treating a CNS or PNS disorder characterized by neuronal damage or depletion in an individual suffering from said damage or depletion the method comprising administering to said individual a composition comprising a 5HT1A agonist, in an amount effective to induce differentiation of neural stem cells of said individual preferentially into neurons, thereby alleviating said damage or depletion.
- 26. A method of treating a CNS or PNS disorder characterized by neuronal damage or depletion in an individual suffering from said damage or depletion the method comprising implanting to said individual a composition comprising a population of neurons that have been differentiated in vitro from human neural stem cells by a method comprising exposure of said stem cells to a 5HT1A agonist in an amount effective to alleviate said damage or depletion.
- 27. The method of claim 24, wherein the disorder is a chronic disorder selected from the group consisting of diabetic peripheral neuropathy, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's Chorea and Parkinson's disease.
- 28. The method of claim 24 wherein said disorder is Alzheimer's disease.
- 29. The method of claim 24, wherein the disorder is an acute disorder selected from the group consisting of stroke, schizophrenia, epilepsy, and injury of the brain, peripheral nerves or spinal cord.
- 30. The method of claim 25, wherein the disorder is a chronic disorder selected from the group consisting of diabetic peripheral neuropathy, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's Chorea, psychiatric depression, bipolar disorder and autism and Parkinson's disease.
- 31. The method of claim 25 wherein said disorder is Alzheimer's disease.
- 32. The method of claim 25, wherein the disorder is an acute disorder selected from the group consisting of stroke, schizophrenia, epilepsy, and injury of the brain, peripheral nerves or spinal cord.
- 33. The method of claim 24 wherein the 5HT1A agonist is buspirone.
- 34. The method of claim 24, wherein the 5HT1A agonist is serotonin.
- 35. The method of claim 25 wherein the 5HT1A agonist is buspirone.
- 36. The method of claim 25, wherein the 5HT1A agonist is serotonin.
- 37. The method of claim 24, further comprising administering to said subject an amount of BDNF in an amount effective to aid in said differentiation of neural stem cells preferentially into neurons.
- 38. The method of claim 25, wherein the differentiated neurons have been differentiated in vitro by a method further comprising exposing human stem cells to BDNF.
- 39. A method for identifying a compound that affects differentiation of mammalian neural stem cells comprising:
- 40. The method of claim 39, wherein the 5HT1A agonist is buspirone.
- 41. The method of claim 39 wherein the 5HT1A agonist is serotonin.
- 42. A method for identifying lead compounds for treatment of CNS disorders characterized by neuronal damages or depletion, comprising:
- 43. The method of claim 42, wherein the 5HT1A agonist is buspirone.
- 44. The method of claim 42, wherein the 5HT1A agonist is serotonin.
- 45. A method for identifying new drug candidates for treatment of CNS disorders characterized by neuronal damages or depletion, comprising:
- 46. The method of claim 45, wherein the 5HT1A agonist is buspirone.
- 47. The method of claim 45, wherein the 5HT1A agonist is serotonin.
Cross Reference to Related Applications
[0001] This application claims priority from U.S. Provisional Application Serial No. 60/299,152, filed June 18, 2001, hereby incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60/299,152 |
Jun 2001 |
US |