| 会長招聘講演 |
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| 2L2
Is delivery a critical period in the pathogenesis of autism?
Ben-Ari Yehezkel
INMED
The developing brain is not a small adult brain. The immature brain undergoes progressive alterations in molecular composition and in synchronized currents that enable neurons to fire and wire together and construct functional neuronal circuits. In the immature brain, large, synchronized patterns of neuronal activity engage many or possibly most neurons of developing brain networks, and are in contrast with the sparse firing, time-locked behaviourally relevant oscillations that occur in the adult nervous system. As well as the gradual and progressive molecular and brain activity changes that occur during development, there is also a large step-change during delivery（i.e. birth）that involves the maturation of various systems including microbiotic, endocrine, vascular and immunological. In contrast to the extensive amount of clinical, epidemiological and experimental information available on the links between genetic mutations and the cellular-molecular pathology of brain disorders, little is known on the impact they have on the sequential transition of brain activity characteristics during development and particularly birth. Collectively, these observations raise the possibility that the deleterious effects of intrauterine genetic mutations and environmental insults are mediated by the deviation of these developmental sequences of changing brain activity. It also raises the possibility that if these immature signatures persist into maturity, they are likely to continue to disrupt brain function over a lifetime. I have suggested the neuro-archeology concept according to which the persistence of these immature currents is instrumental in the subsequent clinical manifestations and a way to develop novel strategies based on specific antagonists that block immature currents in an adult brain. I shall illustrate this with our recent discoveries showing that in animal models of autism, the delivery GABA excitatory to inhibitory shift is abolished and its restoration by maternal administration of a diuretic attenuates the electrical and behavioural manifestation of autism in young and adult off springs. I suggest that delivery confirms, attenuates or aggravates embryonic pathogenic mechanisms. I shall also show the results of our clinical trials with a diuretic that confirm the usefulness of drugs that block immature properties in an adult pathological brain. | | | |
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