All neurons in our brain are wired via a micron-sized connection unit called synapse, and each synapse contains a layer of densely-packed, protein rich compartment called postsynaptic density (PSD), which is responsible for brain signal processing and transmission.
Mutations of genes encoding PSD proteins are major causes of psychiatric disorders including autisms, schizophrenia, and intellectual disabilities (ID). While the existence of PSDs has been known to scientists for 60 years, how PSDs form and change in response to brain activities are poorly understood.
Autism
Autism is a neurodevelopmental disorder typically characterized by impaired social and communication skills combined with repetitive movements.
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‘Autistic symptoms appear when mutations of proteins in the postsynaptic density compartments of the neurons causes hyper-excited synapses or connection-units that link the neurons.’
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In a recent study, scientists from The Hong Kong University of Science and Technology (HKUST) discover that SynGAP and PSD-95, two abundance proteins in PSD that are known to cause autisms when mutated, can form an autonomously assembled network structure both in test-tube and in living cells. Most surprisingly, the SynGAP/PSD-95 assembly can form stable "oil-like" droplets in the midst of aqueous cytoplasm of living cells via a phenomena called phase-transition.
This finding provides a possible answer for the long-lasting question of PSD formation in the field of brain science. Importantly, the HKUST team also found that defects of SynGAP or PSD-95 identified in autism patients alter the "oil-like" droplets formation of the complex and change the synaptic signaling activity of neurons.
![Diabetes Drug Metformin Decreases Weight Gain in Children With Autism]( "Diabetes Drug Metformin Decreases Weight Gain in Children With Autism")
Young people with autism are given antipsychotic medications that are likely to increase weight. A new study claims that metformin could counteract the side effect.
Their research was published in the journal Cell.
"SynGAP and PSD-95 are famous for their roles in learning and memory as well as their involvements in diseases like autisms and epilepsy when mutated, but exactly how these two proteins carry out their functions are not very clear" said Professor Mingjie Zhang, leader of the research group.
"Our studies of the SynGAP/PSD-95 complex, via a multifaceted approach, led to an unexpected finding that living neurons can "borrow" a very fundamental phenomena called phase-transition to place different functional units at specific cellular locations". Prof. Zhang added, "everyone has seen phase transition in our daily life. Liquid water turning into ice is a form of phase transition. Living cells can selectively "pick" certain proteins or nucleic acids to undergo phase transition forming a non-membrane-enclosed cellular compartments, so their physiological functions can be regulated."
"Our work also provides mechanistic insights into why mutations altering the SynGAP/PSD-95 interaction can contribute to various brain disorders including seizure, autism, and ID, a spectrum of central nervous system diseases that have no treatments. We believe that our discovery will also inspire new ways to develop therapeutic methods for these devastating diseases to human society", said. Menglong Zeng, the paper's first author and a Ph.D. student in Prof. Zhang's laboratory.
"This study is only the beginning of teasing out how other proteins collectively contribute to the formation and brain activity-dependent alterations of PSD." Prof. Zhang said. "We are also interested in trying to find out whether other synapses, the neuron/muscle connections for an example, also adopt the phase-transition strategy to build their PSDs".
Source: Medindia
Diabetes Drug Metformin Decreases Weight Gain in Children With Autism
Young people with autism are given antipsychotic medications that are likely to increase weight. A new study claims that metformin could counteract the side effect.
Advertisement
Their research was published in the journal Cell.
"SynGAP and PSD-95 are famous for their roles in learning and memory as well as their involvements in diseases like autisms and epilepsy when mutated, but exactly how these two proteins carry out their functions are not very clear" said Professor Mingjie Zhang, leader of the research group.
"Our studies of the SynGAP/PSD-95 complex, via a multifaceted approach, led to an unexpected finding that living neurons can "borrow" a very fundamental phenomena called phase-transition to place different functional units at specific cellular locations". Prof. Zhang added, "everyone has seen phase transition in our daily life. Liquid water turning into ice is a form of phase transition. Living cells can selectively "pick" certain proteins or nucleic acids to undergo phase transition forming a non-membrane-enclosed cellular compartments, so their physiological functions can be regulated."
"Our work also provides mechanistic insights into why mutations altering the SynGAP/PSD-95 interaction can contribute to various brain disorders including seizure, autism, and ID, a spectrum of central nervous system diseases that have no treatments. We believe that our discovery will also inspire new ways to develop therapeutic methods for these devastating diseases to human society", said. Menglong Zeng, the paper's first author and a Ph.D. student in Prof. Zhang's laboratory.
"This study is only the beginning of teasing out how other proteins collectively contribute to the formation and brain activity-dependent alterations of PSD." Prof. Zhang said. "We are also interested in trying to find out whether other synapses, the neuron/muscle connections for an example, also adopt the phase-transition strategy to build their PSDs".
Source: Medindia
Quiz on Autism
It is difficult to distinguish between the myths and facts where autism is concerned. Test your knowledge on the facts of autism with this quiz.
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 Prenatal Exposure to Chemicals Banned Decades Ago Linked to Risk Of AutismChildren born after exposure to the highest levels of chemicals, called organochlorine, during their mother's pregnancy were 80% likely to be diagnosed with autism. | Advertisement
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