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Review
.2022 Aug 31;10(9):518.
doi: 10.3390/toxics10090518.

Inflammation and Autophagy: A Convergent Point between Autism Spectrum Disorder (ASD)-Related Genetic and Environmental Factors: Focus on Aluminum Adjuvants

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Review

Inflammation and Autophagy: A Convergent Point between Autism Spectrum Disorder (ASD)-Related Genetic and Environmental Factors: Focus on Aluminum Adjuvants

Loïc Angrand et al. Toxics..

Erratum in

Abstract

Autism spectrum disorder (ASD), schizophrenia, and bipolar disorder are genetically complex and heterogeneous neurodevelopmental disorders (NDDs) resulting from genetic factors and gene-environment (GxE) interactions for which onset occurs in early brain development. Recent progress highlights the link between ASD and (i) immunogenetics, neurodevelopment, and inflammation, and (ii) impairments of autophagy, a crucial neurodevelopmental process involved in synaptic pruning. Among various environmental factors causing risk for ASD, aluminum (Al)-containing vaccines injected during critical periods have received special attention and triggered relevant scientific questions. The aim of this review is to discuss the current knowledge on the role of early inflammation, immune and autophagy dysfunction in ASD as well as preclinical studies which question Al adjuvant impacts on brain and immune maturation. We highlight the most recent breakthroughs and the lack of epidemiological, pharmacokinetic and pharmacodynamic data constituting a "scientific gap". We propose additional research, such as genetic studies that could contribute to identify populations at genetic risk, improving diagnosis, and potentially the development of new therapeutic tools.

Keywords: aluminum adjuvants; autism spectrum disorder; autophagy; early exposure; environment; immune system; neurodevelopmental disorders; neurotoxicity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
TEM analysis of Al particles in commercial suspensions (a,c,e) and their related vaccines (b,d,f). (a,b) Al oxyhydroxide, (c,d) Al hydroxyphosphate, and (e,f) mix of both Al adjuvants. Reprinted from [112].
Figure 2
Figure 2
Iba1+ microglial cell density in the ventral forebrain. Iba-1 immunostaining showed a slight increase in the microglial cell density in the group of mice injected with Alhydrogel® 200 µg Al/kg. (a) Control mice injected with PBS; (b) mice injected with Alhydrogel® 200 µg Al/kg; (c) quantification of the microglial cell density. Three mice/group; results expressed as mean ± S.E.M, ANOVA test with post-hoc Bonferroni test, *p < 0.05; scale bars: 50 µm. Reprinted and adapted from [164].
Figure 3
Figure 3
Intracellular aluminum in cells morphologically compatible with microglia within the parietal and temporal lobes of 29-year-old (A8) and 15-year-old (A4) male donors diagnosed with autism. Lumogallion-reactive extracellular aluminum (white arrows) producing an orange fluorescence emission was noted around likely microglial cells in the parietal (a) and temporal lobes (b) of donors A8 and A4, respectively. Non-stained adjacent (5 μm) serial sections produced a weak green autofluorescence emission of the identical area imaged in white (c) and gray matter (d) of the respective lobes. Upper and lower panels depict magnified inserts, marked by asterisks, of the fluorescence channel and brightfield overlay. Magnification ×400, scale bars: 50 μm. Copyright Elsevier (2018) [224].
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