Prof. Dr. Vladimir Trajkovski

Autism
Spectrum Disorders (ASD) are neurodevelopmental disorders characterized
by varying deficits in social interactions, communication, and
learning, as well as stereotypic behaviors. Despite the significant
increase in ASD, there are few if any clues for its pathogenesis,
hampering early detection or treatment. Premature babies are also more
vulnerable to infections and inflammation leading to neurodevelopmental
problems and higher risk of developing ASD. Many autism "susceptibility"
genes have been identified, but "environmental" factors appear to play a
significant role. Increasing evidence suggests that there are different
ASD endophenotypes.

We review relevant
literature suggesting in utero inflammation can lead to preterm labor,
while insufficient development of the gut-blood-brain barriers could
permit exposure to potential neurotoxins. This risk apparently may
increase in parents with "allergic" or autoimmune problems during
gestation, or if they had been exposed to stressors. The presence of
circulating auto-antibodies against fetal brain proteins in mothers is
associated with higher risk of autism and suggests disruption of the
blood-brain-barrier (BBB). A number of papers have reported increased
brain expression or CSF levels of proinflammatory cytokines, especially
TNF, which is preformed in mast cells. Recent evidence also indicates
increased serum levels of the pro-inflammatory mast cell trigger
neurotensin (NT), and of extracellular mitochondrial DNA (mtDNA), which
is immunogenic. Mutations of the signal-transduction molecule mTOR and
its negative regulator Pten have been linked to autism, but also with
proliferation and function of mast cells.

Premature
birth and susceptibility genes may make infants more vulnerable to
allergic, environmental, infectious, or stress-related triggers that
could stimulate mast cell release of pro-inflammatory and neurotoxic
molecules, thus contributing to brain inflammation and ASD pathogenesis,
at least in an endophenotype of ASD patients.