Modulation of Synaptogenesis

Abstract

Soluble proteins, e.g. Hevin, can trigger synapse formation; and other soluble proteins, e.g. SPARC antagonize this activity. Such proteins are synthesized in vitro and in vivo by astrocytes. Methods are provided for protecting or treating an individual suffering from adverse effects of deficits in synaptogenesis, or from undesirably active synaptogenesis.

What is claimed is: 
     
         1 . A method of modulating synaptogenesis comprising the step of:
 contacting a central nervous system neuronal cell with an effective dose of a Hevin agonist or antagonist agent; wherein the synaptogenesis is modulated.   
     
     
         2 . The method of  claim 1 , wherein the neuronal cell is present in vivo. 
     
     
         3 . The method of  claim 1 , wherein the neuronal cell is present in vitro. 
     
     
         4 . The method according to  claim 1 , wherein synaptogenesis is enhanced. 
     
     
         5 . The method of  claim 4 , wherein the agent is a Hevin agonist. 
     
     
         6 . The method of  claim 5 , wherein the agent is a Hevin polypeptide. 
     
     
         7 . The method of  claim 1 , wherein synaptogenesis is reduced. 
     
     
         8 . The method of  claim 7 , wherein said agent is SPARC or an agonist of SPARC. 
     
     
         9 . The method of  claim 2 , wherein the neuronal cell is present in an individual that has suffered synapse loss as a result of senescence. 
     
     
         10 . The method of  claim 2 , wherein the neuronal cell is present in an individual that has suffered synapse loss as a result of Alzheimer's disease 
     
     
         11 . The method of  claim 2 , wherein the neuronal cell is present in an individual that has suffered a CNS or spinal cord injury. 
     
     
         12 . The method of  claim 2 , wherein said neuronal cell is a retinal ganglion cell in an individual with glaucoma. 
     
     
         13 . The method of  claim 2 , further comprising administration of neural progenitors, or a neurogenesis enhancer. 
     
     
         14 . The method of  claim 3 , wherein the neuron is present in an individual that has epilepsy. 
     
     
         15 . The method of  claim 1 , wherein said synaptogenesis is at a neuromuscular junction. 
     
     
         16 . A composition for promoting or inhibiting synaptogenesis comprising:
 an effective amount of a Hevin agonist or antagonist sufficient to promote or inhibit synaptogenesis; and   a pharmaceutically acceptable carrier.   
     
     
         17 . A method of screening a candidate agent for activity in enhancing synaptogenesis, the method comprising:
 contacting a neural cell culture with a candidate agent, wherein said agent is an antagonist or agonist of Hevin signaling;   quantitating the formation of synapses in culture.