Luikart Lab<\/a> is focused on understanding the molecular mechanisms that direct the formation of synapses onto new neurons as they integrate into the synaptic circuitry of the central nervous system.<\/p>\nThe PTEN gene normally functions to control cell growth and also regulates the ability of neurons to alter the strength of their connections. \u201cIn previous studies, we found that removal of this gene in mice results in the overgrowth of neurons leading to hyper-connected neural circuits,\u201d Luikart says. \u201cWe therefore believe that this neuronal circuit hyper-connectivity could be the fundamental basis for the symptoms exhibited by ASD patients.\u201d<\/p>\n
In their new study, Luikart and his team sought to determine if the mutations found in patients would cause the same type of neuronal overgrowth that is seen when the normal healthy gene is completely removed from the neurons of mice.<\/p>\n
![\"\"](\"https:\/\/geiselmed.dartmouth.edu\/news\/wp-content\/uploads\/sites\/2\/2018\/01\/Luikart-pten.jpg\")
<\/p>\n
To do this, they established a method to mimic the genetic defects found in human autism patients\u2014by engineering viruses to \u201cknock out\u201d the normal mouse PTEN gene and replace it with the mutated human PTEN gene\u2014and then used sophisticated imaging and electrophysiological techniques to study how neuronal function was altered in the mice.<\/p>\n
\u201cWe found that putting human PTEN-bearing mutations that have been identified in patients into the neurons of living mice indeed results in the neurons growing abnormally large,\u201d he says, \u201cproving that ASD-associated mutations in the PTEN gene make it unable to regulate the normal growth of neurons in the living mouse brain.\u201d<\/p>\n
In addition, the researchers identified a type of mutation in PTEN that causes the protein to no longer function in the nucleus of the cell.<\/p>\n
\u201cPreviously, it was believed that PTEN at the cell membrane regulates cellular growth,\u201d says Luikart. \u201cWhile this remains true, we determined that PTEN in the nucleus is also capable of regulating cellular growth. Importantly, we found that if we could force the ASD-associated mutant PTEN into the nucleus of the cell, we could partially restore the size of the neuron.<\/p>\n
\u201cThis discovery gives us new insight into how PTEN works to regulate neuronal growth, and suggests that a strategy regulating the location of PTEN within cells could be therapeutic for autism spectrum disorders.\u201d<\/p>\n
<\/p>\n","protected":false},"excerpt":{"rendered":"
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