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    Home > Active Ingredient News > Study of Nervous System > Following the ATP antidepressant, Professor Gao Tianming has another masterpiece: ATP has the potential to treat autism

    Following the ATP antidepressant, Professor Gao Tianming has another masterpiece: ATP has the potential to treat autism

    • Last Update: 2021-06-17
    • Source: Internet
    • Author: User
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    Click on the blue letters to pay attention to our astrocytes participating in the pathogenesis of autism: After an autopsy of autism, the brain tissue shows that the markers of astrocytes in the brain have changed significantly
    .

    Astrocytes derived from human induced pluripotent stem cells can rescue neuronal morphology and synaptic defects derived from ASD patients
    .

    The activation of astrocytes is mainly manifested by the enhancement of calcium ion signal mediated by the endoplasmic reticulum inositol triphosphate type 2 receptor (IP3R2), and the IP3R2 gene is a risk factor for autism
    .

    On May 31, 2021, the research team of Professor Tianming Gao and Associate Professor Yang Jianming of Southern Medical University published an article in Nature Communications, revealing that calcium signals on astrocytes regulate autism-like behavioral disorders in mice
    .

    Knockout of IP3R2 can cause autistic behavioral disorders in mice.
    IP3R2 knockout mice and specific knockout IP3R2 mice on astrocytes (hereinafter referred to as specific IP3R2 knockout) mice can show obvious social disorders , Repetitive stereotypes and other autism-like core symptoms
    .

    Gone are the days of [labeling astrocytes with unsatisfactory results]! The medial prefrontal cortex (mPFC) brain area is a key brain area that causes social dysfunction in autism
    .

    The researchers used shRNA interference technology of the GFAP promoter to specifically knock down IP3R2 on astrocytes in the mPFC brain region, which can cause significant social behavior disorders
    .

    IP3R2 knockout mice and specific IP3R2 knockout mPFC brain area astrocyte-derived ATP levels were significantly reduced, and the ATP content in peripheral organs did not change
    .

    This indicates that the knockout of IP3R2 can specifically cause the level of ATP derived from astrocytes to decrease
    .

    The researchers further found that the decrease in ATP was mainly due to the extracellular level of ATP, and there was no change in intracellular ATP
    .

    The decrease in extracellular levels may be due to a decrease in the release of ATP, or an increase in degradation of ATP by extracellular ATPases (ecto-ATPases)
    .

    They used the fluorescent probe ATP1.
    0, which can dynamically monitor changes in ATP concentration in real time, and found that the release of ATP in IP3R2 knockout mice was reduced after chronic activation of astrocytes
    .

    In addition, the expression of extracellular ATPases ENPP1 and ENTPD3 increased in IP3R2 knockout mice
    .

    In vitro cell experiments found that the astrocytes isolated from IP3R2 knockout mice had a significant increase in ATP concentration after incubating with ATPase inhibitors
    .

    The above suggests that the decrease in extracellular ATP levels may be due to a combination of decreased ATP release and increased ATP degradation
    .

    Reversal of social disorder behavior in IP3R2 knockout mice after ATP injection A single dose of intraperitoneal injection of ATP can effectively reverse the social disorder behavior in IP3R2 knockout mice, but it cannot alleviate repetitive stereotyped behavior disorders.
    This therapeutic effect is dose-dependent
    .

    Injection of non-hydrolyzable ATP analogues into the lateral ventricles or brain regions of mPFC of specific IP3R2 knockout mice can also significantly improve their social disorders
    .

    Electrophysiological experiments found that the spontaneous excitatory postsynaptic current of mPFC brain area pyramidal neurons in IP3R2 knockout mice or specific IP3R2 knockout mice did not change, but the spontaneous inhibitory postsynaptic current decreased
    .

    The administration of GABAAR agonists can also significantly improve the social disorders of the above two types of knockout mice
    .

    It indicates that knocking out IP3R2 may cause inhibitory synaptic transmission disorder of pyramidal neurons in the mPFC brain area
    .

    Injection of ATP analogs does not affect the synaptic transmission function of normal mice, but can reverse the inhibitory synaptic transmission disorder caused by knocking out IP3R2
    .

    This indicates that the loss of IP3R2 in astrocytes causes synaptic dysfunction, which may be a key step in causing autism-like behavior
    .

    The virus knocks down the P2X2 receptor in the brain region of mPFC.
    Previous studies have shown that ATP regulates GABAergic synaptic transmission through the P2X2 receptor (a cell membrane receptor that can bind to ATP)
    .

    After the researchers silenced the P2X2 receptor in the brain region of mPFC with a viral vector, normal mice showed obvious social barriers and inhibitory synaptic transmission disorders; it was able to block ATP treatment of specific IP3R2 knockout mice with autism-like behavior disorder Effect
    .

    This indicates that the P2X2 receptor is a key molecule for ATP to play an anti-autistic effect
    .

    In summary, this article found that astrocyte-derived ATP regulates autism-like behavioral disorders through P2X2 receptors
    .

    [References] 1.
    https://doi.
    org/10.
    1038/s41467-021-23843-0, the pictures in the text are all from the reference original download link: Baidu Netdisk https://pan.
    baidu.
    com/s/1AvS5wFeYOkXngVmqlhuYjQ Extraction code: jnve 
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