Recently we have solubilized and characterized several high affinity serotonin binding proteins from cortex. In addition, we have shown that a subgroup of autistic children possess antibodies directed against these sites. In an extension of these studies, this proposal outlines strategies to isolate and/or develop antibodies against human brain serotonin binding proteins. The long-term objectives of these approaches are to develop and utilize immunological tools to better define the contributions of neurotransmitter receptors and immunologic mechanisms to normal neurodevelopment and severe psychiatric disorders of childhood: in particular, infantile autism. Specifically, monoclonal and polyclonal antibodies to cortical serotonin binding proteins will be identified or produced by various methods. Serotonin type 1A, type 1B and type 3 binding sites (5-HT-1A, 5-HT-1B, 5-HT-3 proteins) will be partially purified from human cortex in microgram quantities by previously described techniques (detergent solubilization and affinity chromatograph). These proteins will be used to immunize murine lymphocytes in vitro. Competent lymphocytes will be fused with a murine myeloma cell line and resulting hybridomas screened for anti-serotonin-binding-protein antibody production. Additional autistic children will be screened for the production of autoantibodies directed against serotonin binding proteins (Todd, R.D. and Ciaranello, R.D., Proc. Natl. Acad. Science, in press). The serum of antibody positive children will be used as a source of polyclonal antibodies. B-lymphocytes from antibody positive children will be fused with a human myeloma cell line and resultant hybridomas screened for production of monoclonal anti-serotonin-binding-protein antibodies. The proposed approaches will give immunological tools with different specificities. These antibodies will be used in future studies to define the gross and microscopic distributions of serotonin binding protein subtypes, study structural similarities between subtypes, and to determine the functional consequences of anti-serotonin-binding-protein antibodies in vitro and in vivo.
| Todd, R D (1992) Neural development is regulated by classical neurotransmitters: dopamine D2 receptor stimulation enhances neurite outgrowth. Biol Psychiatry 31:794-807 |
| Sikich, L; Hickok, J M; Todd, R D (1990) 5-HT1A receptors control neurite branching during development. Brain Res Dev Brain Res 56:269-74 |
| Sikich, L; Todd, R D (1988) Are the neurodevelopmental effects of gonadal hormones related to sex differences in psychiatric illnesses? Psychiatr Dev 6:277-309 |
| Todd, R D; Bauer, P A (1988) Ascorbate modulates 5-[3H]hydroxytryptamine binding to central 5-HT3 sites in bovine frontal cortex. J Neurochem 50:1505-12 |
| Todd, R D; Ciaranello, R D (1987) Multiple high-affinity [3H]serotonin binding sites in human frontal cortex. Brain Res 400:247-58 |
| Todd, R D; Babinski, J (1987) A thermodynamic study of 5-[3H]hydroxytryptamine binding to human cortex membranes. J Neurochem 49:1480-3 |
| Todd, R D (1986) Pervasive developmental disorders and immunological tolerance. Psychiatr Dev 4:147-65 |
