Being born is not easy. Mammals need to pass through the birth canal before coming out into this world, and to do so the head (and whole body) undergoes a harsh squeezing. Thankfully, the newborn prepares for this stressful event that transitions life from in-utero to ex-utero. But these events (some, or all of them) … Smaller brain volumes after birth by Cesarean Section
The activity of the neurotransmitter GABA, the main inhibitory transmitter in the brain, follows a developmental sequence. In early development GABA excites neurons via type A GABA receptors (GABAAR), and later it inhibits them. In addition, during the critical period of birth, as a protective mechanism, GABA becomes temporarily inhibitory. Five years ago, we showed … The GABA developmental sequence is altered in a mouse model of Rett Syndrome
How does the brain prepare for birth? Several indirect lines of evidence in Humans suggest that the velocity at which the brain grows in utero slows down during the third trimester, a process that will make sense knowing that the head should be able to fit through the birth canal during delivery. In our recent … No stop-growing signal around birth in a rodent model of autism
Two of the most biologically complex and vulnerable periods are pregnancy and birth. Birth is a stressful event with a release of several stress molecules needed to facilitate the transition of the fetus to extrauterine life. Furthermore, throughout pregnancy the fetus is susceptible to different types of stressors including immune activation due to maternal infections … Immune activation during gestation leads to hippocampal neuronal alterations already at birth
In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl−)i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3–11 years old). Here we report the results of a multicentre … A promising multicenter trial to alleviate autistic disorders
The scientific community agrees on the early origin – fetal and/or early postnatal – of autism. The teams of Yehezkel Ben-Ari (CEO of Neurochlore and Emeritus Research Director at Inserm) at Neurochlore and at the Mediterranean Neurobiology Institute (Inmed), have just taken a new step in understanding the early manifestations of the disease. The researchers … The diuretic Bumetanide and the birth hormone Oxytocin point to a common pathway in the early pathogenesis of Autism in rodents
We report that daily administration of the diuretic NKCC1 chloride co-transporter, bumetanide, reduces the severity of autism in a 10-year-old Fragile X boy using CARS, ADOS, ABC, RDEG and RRB before and after treatment. In keeping with extensive clinical use of this diuretic, the only side effect was a small hypokalaemia. A double-blind clinical trial … Treating Fragile X syndrome with the diuretic bumetanide: a case report
Gamma aminobutyric acid (GABA)-mediated synapses and the oscillations they orchestrate are altered in autism. GABA-acting benzodiazepines exert in some patients with autism paradoxical effects, raising the possibility that like in epilepsies, GABA excites neurons because of elevated intracellular concentrations of chloride. Following a successful pilot study,(1) we have now performed a double-blind clinical trial using … A randomised controlled trial of bumetanide in the treatment of autism in children
Ionic currents and the network-driven patterns they generate differ in immature and adult neurons: The developing brain is not a “small adult brain.” One of the most investigated examples is the developmentally regulated shift of actions of the transmitter GABA that inhibit adult neurons but excite immature ones because of an initially higher intracellular chloride … The GABA excitatory/inhibitory shift in brain maturation and neurological disorders