Περίληψη:
Background: 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.
Discussion: 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
cerebrospinal fluid (CSF) levels of pro-inflammatory cytokines,
especially TNF, which is preformed in mast cells. Recent evidence also
indicates increased serum levels of the proinflammatory mast cell
trigger neurotensin (NT), and of extracellular mitochondrial DNA
(mtDNA), which is immunogenic. Gene mutations of phosphatase and tensin
homolog (PTEN), the negative regulator of the mammalian target of
rapamycin (mTOR), have been linked to higher risk of autism, but also to
increased proliferation and function of mast cells.
Summary: 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.
Συγγραφείς:
Angelidou, Asimenia
Asadi, Shahrzad
Alysandratos,
Konstantinos-Dionysios
Karagkouni, Anna
Kourembanas, Stella and
Theoharides, Theoharis C.
