Abstract: Disclosed herein are methods for differentiation of neuronal cells from stem cells, which produce a three-dimensional model of the neocortex structure. In some embodiments, the methods include culturing stem cells with at least one inhibitor of SMAD signaling and at least one inhibitor of fibroblast growth factor signaling for a period of time to result in formation of an embryoid body. The embryoid body is then cultured with at least one FGF (for example, basic FGF) for a period of time sufficient to produce a neuroepithelial (NE) rosette. The rosette is then isolated and cultured in suspension or adherent culture in the presence of at least one FGF for a period of time sufficient to produce cells with dorsal cortical identity and those cells are then cultured in the substantial absence of trophic factors for a period of time sufficient to form a neocortical organoid.

Abstract: Disclosed are methods that include separately differentiating stem cells to form cortical neural progenitor cells and differentiating stem cells to form dopaminergic neural progenitor cells. The cortical progenitor cells are transferred to a first compartment of a culture dish and the dopaminergic progenitor cells are transferred to a second compartment of the culture dish, separated by a removable barrier. The cortical progenitor cells and dopaminergic progenitor cells are cultured in medium that promotes differentiation of cortical neurons and dopaminergic neurons, respectively. The barrier is then removed, creating a single chamber containing the cortical progenitor cells and the dopaminergic progenitor cells, separated by a gap.

Abstract: Disclosed are methods that include separately differentiating stem cells to form cortical neural progenitor cells and differentiating stem cells to form dopaminergic neural progenitor cells. The cortical progenitor cells are transferred to a first compartment of a culture dish and the dopaminergic progenitor cells are transferred to a second compartment of the culture dish, separated by a removable barrier. The cortical progenitor cells and dopaminergic progenitor cells are cultured in medium that promotes differentiation of cortical neurons and dopaminergic neurons, respectively. The barrier is then removed, creating a single chamber containing the cortical progenitor cells and the dopaminergic progenitor cells, separated by a gap.

Abstract: Disclosed herein are methods for differentiation of neuronal cells from stem cells, which produce a three-dimensional model of the neocortex structure. In some embodiments, the methods include culturing stem cells with at least one inhibitor of SMAD signaling and at least one inhibitor of fibroblast growth factor signaling for a period of time to result in formation of an embryoid body. The embryoid body is then cultured with at least one FGF (for example, basic FGF) for a period of time sufficient to produce a neuroepithelial (NE) rosette. The rosette is then isolated and cultured in suspension or adherent culture in the presence of at least one FGF for a period of time sufficient to produce cells with dorsal cortical identity and those cells are then cultured in the substantial absence of trophic factors for a period of time sufficient to form a neocortical organoid.

Abstract: Methods for differentiating stem cells are disclosed herein. These methods can be used to generate neurons, including, but not limited to, dopaminergic neurons. The disclosed methods include culturing stem cells in the absence of fibroblast growth factor-2 to generate embryoid bodies and culturing the embryoid bodies in the presence of an effective amount of at least one of stromal cell-derived factor 1, pleiotrophin, insulin-like growth factor 2, and ephrin B1 on an extracellular matrix for a period of time sufficient to produce dopaminergic neuronal cells. The differentiated cells can be used to study pharmaceutical agents that affect dopaminergic neurons and can be used in the treatment of neurodegenerative disorders such as Parkinson's disease.

Abstract: Methods for differentiating stem cells are disclosed herein. These methods can be used to generate neurons, including, but not limited to, dopaminergic neurons. The disclosed methods include culturing stem cells in the absence of fibroblast growth factor-2 to generate embryoid bodies and culturing the embryoid bodies in the presence of an effective amount of at least one of stromal cell-derived factor 1, pleiotrophin, insulin-like growth factor 2, and ephrin B1 on an extracellular matrix for a period of time sufficient to produce dopaminergic neuronal cells. The differentiated cells can be used to study pharmaceutical agents that affect dopaminergic neurons and can be used in the treatment of neurodegenerative disorders such as Parkinson's disease.

Abstract: The present invention provides a method of treating a neuropsychiatric disease characterized by an abnormally elevated level of a fragment of an isoform of a neural cell adhesion molecule, N-CAM, in the brain or cerebrospinal fluid of an affected human subject, comprising administering a therapeutically effective amount of at least one compound selected from the group consisting of protease inhibitors and neuraminidase inhibitors, whereby administering the compound to the subject treats the human subject. The present invention further provides a method of monitoring the efficacy of treatment with the method of the present invention. Moreover, the present invention provides a method of screening for compounds effective in treating neuropsychiatric disease associated with an abnormally elevated level of a fragment of a neural cell adhesion molecule in the cerebrospinal fluid of an affected human subject. Further provided are fragments of an isoform of N-CAM in the cerebrospinal fluid of human subjects.

Abstract: The transplantation of donor tissue into the brain is effected by locking the head relative to a stereotaxic unit; penetrating the brain with a first cannula to a predetermined depth to create a transplant site within the brain while the first cannula is fixed by the stereotaxic unit relative to the brain; then feeding a second cannula, which contains donor tissue at its distal end, through the already fixed first cannula so that the distal end of the second cannula comes to rest at the transplant site; and finally withdrawing the first cannula and the second cannula so as to leave the donor tissue at the transplant site.

Abstract: The transplantation of donor tissue into the brain is effected by locking the head relative to a stereotaxic unit; penetrating the brain with a first cannula to a predetermined depth to create a transplant site within the brain while the first cannula is fixed by the stereotaxic unit relative to the brain; then feeding a second cannula, which contains donor tissue at its distal end, through the already fixed first cannula so that the distal end of the second cannula comes to rest at the transplant site; and finally withdrawing the first cannula and the second cannula so as to leave the donor tissue at the transplant site.