Bridging from Cells to Cognition in Autism Pathophysiology: Biological Pathways to Defective Brain Function and Plasticity

Journal Article · Tue Jan 01 04:00:00 EST 2008 · American Journal of Biochemistry and Biotechnology, 4(2):167-176

DOI:https://doi.org/10.1007/s12010-007-8041-y· OSTI ID:944766

Anderson, Matthew; Hooker, Brian S; Herbert, Martha

We review evidence to support the model that autism may begin when a maternal environmental, infectious, or autoantibody insult causes inflammation which increases reactive oxygen species (ROS) production in the fetus, leading to fetal DNA damage (nuclear and mitochondrial), and that these inflammatory and oxidative stressors persist beyond early development (with potential further exacerbations), producing ongoing functional consequences. In organs with a high metabolic demand such as the central nervous system, the continued use of mitochondria with DNA damage may generate additional ROS which will activate the innate immune system leading to more ROS production. Such a mechanism would self-sustain and possibly progressively worsen. The mitochondrial dysfunction and altered redox signal transduction pathways found in autism would conspire to activate both astroglia and microglia. These activated cells can then initiate a broad-spectrum proinflammatory gene response. Neurons may have acquired receptors for these inflammatory signals to inhibit neuronal signaling as a protection from excitotoxic damage during various pathologic insults (e.g., infection). In autism, over-zealous neuroinflammatory responses could not only influence neural developmental processes, but may more significantly impair neural signaling involved in cognition in an ongoing fashion. This model makes specific predictions in patients and experimental animal models and suggests a number of targets sites of intervention. Our model of potentially reversible pathophysiological mechanisms in autism motivates our hope that effective therapies may soon appear on the horizon.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 944766
• Report Number(s): PNNL-SA-54664; 6504a; 17691
• Journal Information: American Journal of Biochemistry and Biotechnology, 4(2):167-176, Journal Name: American Journal of Biochemistry and Biotechnology, 4(2):167-176 Journal Issue: 2 Vol. 4
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ANIMALS
BDNF
BIOLOGICAL PATHWAYS
BRAIN
CENTRAL NERVOUS SYSTEM
DNA DAMAGES
Environmental Molecular Sciences Laboratory
FUNCTIONALS
GENES
INFLAMMATION
MITOCHONDRIA
NERVE CELLS
ORGANS
OXYGEN
PATIENTS
PLASTICITY
ROS
TARGETS
dendritic beading
inflammation
mitochondria
synaptic plasticity