Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits and repetitive behaviors.
The causes are complex, involving genetic and environmental factors that affect brain development.
Growing evidence implicates immune system abnormalities and neuroinflammation in ASD.
Galectin-1 and galectin-3 are proteins that regulate immune responses and inflammation.
A new study found significantly higher blood levels of galectin-1 and galectin-3 in children with ASD compared to siblings and unrelated healthy controls.
This supports the hypothesis that chronic inflammation contributes to ASD pathology.
Key Facts:
- 42 children with ASD, 42 unaffected siblings, and 42 unrelated healthy controls participated.
- Children with ASD had much higher galectin-1 levels than both control groups.
- Galectin-3 was elevated in ASD compared to unrelated controls only.
- Galectin levels did not correlate with autism symptom severity.
- Unaffected siblings did not have raised galectin levels, suggesting they are not ASD endophenotypes.
- Potential mechanisms linking galectins to ASD neuroinflammation are discussed.
Source: Clinical Psychopharmacology & Neuroscience 2023
Autism Spectrum Disorder (ASD), Neuroinflammation, Galectin (1 & 3)
Autism spectrum disorder is characterized by difficulties with social communication and interaction, restricted interests, and repetitive behaviors.
Symptom onset is in early childhood, usually before age 3.
The causes of ASD are complex, involving a combination of genetic, epigenetic and environmental influences.
Despite intense research, the specific etiology and pathogenesis of ASD remain unclear.
The prevalence of ASD has risen dramatically in recent decades.
Current estimates indicate around 1 in 68 children are diagnosed with ASD.
The increase is partly due to improved awareness and diagnosis, but many experts believe environmental factors are also contributing.
This has led to a major research effort to uncover exposures and biological mechanisms that could explain the rise in ASD.
One hypothesis that has gained considerable attention involves immune system abnormalities and neuroinflammation.
Numerous studies have found evidence of chronic inflammation in the brains and bodies of individuals with ASD compared to neurotypical controls.
This includes increased inflammatory markers in the cerebrospinal fluid and blood, as well as activation of microglia and astrocytes in postmortem ASD brain tissue.
Neuroinflammation during critical developmental windows could alter neural connectivity patterns.
Many of the behavioral and cognitive features of ASD could arise from inflammation-induced disruptions in synaptic pruning, connectivity, and plasticity.
This has prompted searches for blood-based inflammatory biomarkers associated with ASD pathogenesis and symptomatology.
Galectin-1 and Galectin-3 are proteins that regulate immune cell responses and neuroinflammation.
Prior studies suggest they could play a role in neurodevelopmental conditions like ASD.
This new study assessed whether children with ASD have altered levels of galectin-1 and galectin-3 compared to their unaffected siblings and unrelated typically developing controls.
Study Evaluating Galectin-1 & Galectin-3 in ASD
The study included 42 children diagnosed with ASD, 42 unrelated healthy controls, and 42 unaffected siblings of the ASD subjects.
Participants were aged between 2-12 years old.
Children with medical conditions or taking medications were excluded.
ASD diagnosis was confirmed using gold-standard diagnostic instruments.
Autism symptom severity was quantified with the Childhood Autism Rating Scale (CARS).
Fasting blood samples were collected from all subjects.
Serum levels of galectin-1 and galectin-3 were measured using enzyme-linked immunosorbent assays.
Statistical analyses compared galectin levels across the three groups, controlling for age, sex, and body mass index.
Associations between galectin levels and autism severity scores were also examined.
Higher Serum Galectin-1 in ASD vs. Non-ASD Siblings
Children with ASD had significantly higher serum concentrations of galectin-1 compared to both their own siblings and unrelated healthy children.
Galectin-3 levels were also elevated in ASD subjects relative to healthy controls, but not siblings.
- Mean galectin-1 in ASD group was 876.7 ng/ml vs 172.9 ng/ml in siblings and 159.1 ng/ml in controls (both p < 0.001)
- Mean galectin-3 in ASD was 7.38 ng/ml vs 5.54 ng/ml in controls (p = 0.013). No significant difference vs siblings.
- No associations were found between galectin levels and autism symptom severity measured by CARS.
Why is Galectin-1 elevated in Autism Spectrum Disorder?
This is the first study examining galectin-1 and galectin-3 blood levels in ASD.
The findings add to evidence that immune system abnormalities and inflammation contribute to ASD pathogenesis.
Galectin-1 is an important regulator of neuroinflammation.
In animal studies, galectin-1 inhibits microglial activation and migration into the central nervous system where it exerts anti-inflammatory effects.
The elevated galectin-1 observed in children with ASD may represent an attempt to counteract existing neuroinflammation.
Galectin-3 enhances inflammatory responses in the brain. It can initiate activation and proliferation of microglia, which are the resident immune cells in the CNS.
Excess galectin-3 amplifies neurotoxic inflammation that can impair neuronal function.
The increased galectin-3 in ASD cases relative to unrelated controls aligns with its pro-inflammatory role.
During early brain development, activated microglia prune unnecessary synapses.
Dysfunctional glial activation and irregular pruning caused by inflammation could manifest in the behavioral profile of ASD.
The similar galectin levels in siblings versus ASD cases may indicate shared genetic or environmental factors that predispose to neuroinflammation.
However, the differences compared to unrelated controls mean galectins are unlikely autism endophenotypes.
Circulating galectin levels did not correlate with autism severity scores on the CARS scale.
Further studies with larger samples would be needed to properly analyze these relationships.
Overall, the altered galectin-1 and galectin-3 levels support the hypothesis that chronic neuroinflammation driven by immune abnormalities contributes to ASD pathogenesis.
This study also adds to evidence that galectin-1 and galectin-3 could be useful blood-based biomarkers of neuroinflammation in ASD and other neurodevelopmental conditions.
Additional research is warranted to further explore their clinical utility.
Elevated Galectin-1 & Galectin-3 in ASD: Persistent Neuroinflammation
This research found significantly elevated levels of the inflammatory marker proteins galectin-1 and galectin-3 in the blood of children with ASD compared to healthy controls.
This aligns with evidence from postmortem brain studies showing neuroinflammation in ASD.
Chronically activated microglia and inflammatory responses during early brain development could alter neuronal connectivity patterns and synaptic pruning, manifesting in cognitive and behavioral deficits characteristic of ASD.
Higher galectin levels may represent regulatory responses aimed at controlling neuroinflammation.
These data lend further support to the theory that immune dysregulation and resulting neuroinflammation play a pathogenic role in ASD.
Additional large studies are needed to verify these findings and determine if galectins could serve as useful biomarkers to monitor neuroinflammation in ASD.
Ultimately, research on the immune system and inflammation pathways could uncover novel drug targets and lead to new treatments for ASD.
References
- Study: Higher levels of galectin-1 and galectin-3 in young subjects with autism spectrum disorder compared to unaffected siblings and healthy controls
- Authors: Zeynep Nur Karadogan et al. (2023)
