The Functions of Glial Cells and Epigenetics in Drug-induced Autism Spectrum Disorder

Ethan Taylor^*
*Correspondence: Ethan Taylor, Department of Clinical Genomics, University of Sydney, Camperdown NSW 2006, Australia, Email:

Keywords

Glial cells • Epigenetics • Drug exposure • Neurodevelopment

Introduction

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction, as well as restricted and repetitive patterns of behavior, interests, or activities. The prevalence of ASD has been steadily increasing over the past few decades, with current estimates suggesting that approximately 1 in 54 children in the United States are diagnosed with ASD. While the exact etiology of ASD remains unclear, it is widely accepted that both genetic and environmental factors contribute to its development [1].

Among the environmental factors implicated in ASD, prenatal exposure to certain drugs has garnered significant attention. Maternal drug use during pregnancy, whether prescribed medications or illicit substances, has been associated with an increased risk of ASD in offspring. This has led researchers to investigate the mechanisms through which these drugs may influence neurodevelopment and contribute to the pathogenesis of ASD. In recent years, there has been growing interest in the role of glial cells in neurodevelopmental disorders, including ASD. Glial cells, once viewed primarily as support cells in the Central Nervous System (CNS), are now recognized for their active roles in synaptic pruning, neurotransmitter regulation, and immune response modulation [2].

Literature Review

Glial cells, including astrocytes, oligodendrocytes, and microglia, constitute the majority of cells in the CNS and play essential roles in supporting neuronal function and maintaining brain homeostasis. Astrocytes, for example, provide metabolic support to neurons, regulate neurotransmitter levels, and participate in synapse formation and plasticity. Oligodendrocytes are responsible for myelinating axons, facilitating efficient neuronal communication, while microglia serve as the brain's immune cells, contributing to synaptic pruning and inflammation regulation. Several lines of evidence suggest that abnormalities in glial cell function may contribute to the pathogenesis of ASD. Postmortem studies have reported alterations in glial cell morphology and density in the brains of individuals with ASD, indicating disrupted glial-neuronal interactions. Furthermore, animal models of ASD have demonstrated dysregulated glial responses to environmental insults, including prenatal drug exposure [3].

Maternal drug use during pregnancy, whether pharmaceutical or recreational, can have profound effects on fetal neurodevelopment. Studies have shown that certain drugs, such as valproic acid (VPA) and thalidomide, are associated with an increased risk of ASD in offspring. These drugs act on various molecular pathways, including those involved in neuronal migration, synaptic plasticity, and neurotransmitter signaling.

One proposed mechanism linking prenatal drug exposure to ASD is through disruption of glial cell function. For example, VPA, a commonly prescribed anticonvulsant and mood stabilizer, has been shown to affect astrocyte development and function in animal models. Similarly, exposure to thalidomide during critical periods of brain development can alter microglial activation and immune response regulation, potentially contributing to neuroinflammation and synaptic pruning deficits observed in ASD. In addition to direct effects on glial cells, prenatal drug exposure can also influence glial function through epigenetic mechanisms. Epigenetics refers to heritable changes in gene expression that do not involve alterations in the DNA sequence. Epigenetic processes, such as DNA methylation, histone modifications, and microRNA regulation, play critical roles in regulating gene expression patterns during development and throughout life [4].

Discussion

The interplay between glial cells and epigenetic processes in drug-induced ASD is a complex and dynamic relationship. Glial cells are not only influenced by epigenetic mechanisms but also actively regulate epigenetic processes within the brain. Astrocytes, for example, can release signaling molecules that modulate DNA methylation and histone acetylation in neighboring neurons and glial cells, thereby influencing gene expression patterns. Conversely, epigenetic changes induced by prenatal drug exposure can impact glial cell function and contribute to neurodevelopmental abnormalities associated with ASD. Studies have shown that aberrant DNA methylation patterns in glial cells can lead to dysregulated immune responses, synaptic pruning deficits, and altered neurotransmitter signaling, all of which are implicated in the pathogenesis of ASD [5].

Understanding the roles of glial cells and epigenetic mechanisms in drug-induced ASD has significant implications for the development of novel therapeutic strategies. Targeting glial dysfunction and aberrant epigenetic marks associated with ASD may offer new avenues for intervention and treatment. For example, pharmacological agents that modulate glial cell function, such as astrocyte-specific activators or microglial inhibitors, could potentially mitigate the neurodevelopmental effects of prenatal drug exposure. Likewise, epigenetic therapies aimed at restoring normal DNA methylation patterns or histone modifications may help reverse the gene expression changes underlying ASD pathology [6].

Conclusion

Epigenetic mechanisms, which involve heritable changes in gene expression without alterations in the DNA sequence, have also emerged as key players in neurodevelopment and ASD. Epigenetic processes, such as DNA methylation, histone modifications, and non-coding RNA regulation, can be influenced by environmental factors, including drug exposure. In conclusion, the functions of glial cells and epigenetic mechanisms play critical roles in drug-induced Autism Spectrum Disorder (ASD). Prenatal drug exposure can disrupt glial cell function, leading to neurodevelopmental abnormalities associated with ASD. Epigenetic changes induced by drugs further exacerbate these effects, altering gene expression patterns critical for brain development and function.

Understanding the interplay between glial cells and epigenetics in druginduced ASD opens new avenues for therapeutic interventions. Targeting glial dysfunction and aberrant epigenetic marks associated with ASD may lead to the development of personalized treatments that address the specific underlying mechanisms driving the disorder.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Bailey, Anthony, Anne Le Couteur, Irving Gottesman and Patrick Bolton, et al. "Autism as a strongly genetic disorder: Evidence from a British twin study." Psychol Med 25 (1995): 63-77.

   Google Scholar, Crossref, Indexed at

2. Rutter, Michael. "Genetic studies of autism: From the 1970s into the millennium." J Abnorm Child Psychol 28 (2000): 3-14.

   Google Scholar, Crossref, Indexed at

3. Kim, Johanna Inhyang, Jung Lee, Kyung-Shin Lee and Young Ah Lee, et al. "Association of phthalate exposure with autistic traits in children." Environ Int 157 (2021): 106775.

   Google Scholar, Crossref, Indexed at

4. El-Ansary, Afaf K., Abir Ben Bacha and Malak Kotb. "Etiology of autistic features: The persisting neurotoxic effects of propionic acid." J Neuroinflamm 9 (2012): 1-14.

   Google Scholar, Crossref, Indexed at

5. Dombrowski, Marco, Maik Engeholm, Christian Dienemann and Svetlana Dodonova, et al. "Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory." Nat Struct Mol Biol 29 (2022): 493-501.

   Google Scholar, Crossref, Indexed at

6. Miller, Jaime L. and Patrick A. Grant. "The role of DNA methylation and histone modifications in transcriptional regulation in humans." Epigenetic: Develop Dis (2012): 289-317.

   Google Scholar, Crossref, Indexed at