摘要:
A method of treating a subject for a serotonergic neurotransmission dysregulation disorder, comprises administering the subject a serotonin enhancer (e.g., a serotonin reuptake inhibitor) in an amount effective to treat the disorder; and concurrently administering the subject 5-hydroxytryptophan in an amount effective to enhance the activity of the serotonin enhancer, (e.g., serotonin reuptake inhibitor). In preferred embodiments the disorder is depression, anxiety, or substance abuse.
摘要:
A method of treating a subject for a serotonergic neurotransmission dysregulation disorder, comprises administering the subject a serotonin enhancer (e.g., a serotonin reuptake inhibitor) in an amount effective to treat the disorder; and concurrently administering the subject 5-hydroxytryptophan in an amount effective to enhance the activity of the serotonin enahancer, (e.g., serotonin reuptake inhibitor). In preferred embodiments the disorder is depression, anxiety, or substance abuse.
摘要:
A method of screening a subject for a serotonergic neurotransmission dysregulation disorder comprises detecting the presence or absence of an Tph2 mutation in the subject; and then determining that the subject is at increased risk of a serotonergic neurotransmission dysregulation disorder due to the presence or absence of the Tph2 mutation.
摘要:
A method of screening a subject for a serotonergic neurotransmission dysregulation disorder comprises detecting the presence or absence of an Tph2 mutation in the subject; and then determining that the subject is at increased risk of a serotonergic neurotransmission dysregulation disorder due to the presence or absence of the Tph2 mutation.
摘要:
A method of screening a candidate compound for βArrestin mediated anti-G protein coupled receptor signaling activity is comprises: (a) contacting said candidate compound to a βArrestin signaling complex or a constituent thereof, under conditions in which a signaling complex is formed; and then (b) detecting the presence or absence of disruption of said signaling complex, disruption of said complex indicating said compound has βArrestin mediated anti-G protein coupled receptor signaling activity. Compositions and kits for carrying out the method are also described.
摘要:
A method of screening a candidate compound for βArrestin mediated anti-G protein coupled receptor signaling activity is comprises: (a) contacting said candidate compound to a βArrestin signaling complex or a constituent thereof, under conditions in which a signaling complex is formed; and then (b) detecting the presence or absence of disruption of said signaling complex, disruption of said complex indicating said compound has βArrestin mediated anti-G protein coupled receptor signaling activity. Compositions and kits for carrying out the method are also described.
摘要:
A method of screening a candidate compound for βArrestin mediated anti-G protein coupled receptor signaling activity is comprises: (a) contacting said candidate compound to a βArrestin signaling complex or a constituent thereof, under conditions in which a signaling complex is formed; and then (b) detecting the presence or absence of disruption of said signaling complex, disruption of said complex indicating said compound has βArrestin mediated anti-G protein coupled receptor signaling activity. Compositions and kits for carrying out the method are also described.
摘要:
Recombinant or transgenic non-human mammals are described having a mutant tryptophan hydroxylase 2 (Tph2) gene resulting in altered synthesis of 5-hydroxytryptophan and serotonin in the brain. In some embodiments the mutant tryptophan hydroxylase 2 gene contains mouse R439H and/or P447R functional mutations, or their corresponding mutations in other species. Congenic non-human mammals having mutant tryptophan hydroxylase 2 genes are also provided. Methods of screening a compound for serotonergic activity or activity in treating a serotonergic neurotransmission dysregulation disorder are provided, which include administering a test compound to a recombinant non-human mammal and then detecting the presence or absence of serotonergic activity, or activity in treating a serotonergic neurotransmission dysregulation disorder, in the mammal. A cell such as a nerve cell (e.g., a central nervous system neuron) isolated from a transgenic or congenic mammal is also disclosed, along with cell cultures containing these cells.
摘要:
Recombinant non-human mammals having reduced or no expression of vesicular acetylcholine transporter protein (VAChT) as compared to the corresponding wild-type mammal are provided. The mammal may have, e.g., impaired performance in object and social recognition and/or impaired neuromuscular performance and/or alterations in autonomic nervous system function as compared to the corresponding wild-type mammal. Methods of screening a compound for cholinergic activity or activity in treating a cholinergic neurotransmission disorder are also provided. In addition, a cell such as a nerve cell isolated from a mammal as described herein is provided, along with cell cultures, which are useful in vitro for screening the activity of candidate compounds for their effect on cholinergic neurotransmission, and for their activity in treating cholinergic neurotransmission disorders.
摘要:
A method of treating a subject for Parkinson's disease comprises administering said subject a phenylisopropylamine in an amount effective to treat said Parkinson's disease. In some embodiments the method is used to treat at least a motor symptom of Parkinson's disease; in some embodiments the method is used to treat at least a non-motor symptom of Parkinson's disease.