Autism Spectrum Disorder Research at the University of California, Irvine

Written by Samantha Ahn and Edited by Gauri Ajith

Michelle S. Kim / University Communications. Image from CART.

Autism Spectrum Disorder (ASD) refers to a specific category of neurodevelopmental impairments characterized by repetitive behaviors and difficulties in communication and social interaction [1]. Autism, or ASD, is currently estimated to affect 1 in 59 children; a prevalence that has continued to rise over the past several decades [2]. Although there is currently no consensus on the development of ASD, it is understood as a complex disorder caused by a combination of genetic and environmental factors [3]. Improvements in ways to analyze genetic information, such as genomic technology (technology used to analyze the sequence of DNA), have expedited the discovery of the factors that increase the susceptibility of developing autism. Of these factors, those involved in the process of calcium signaling within cells have become a compelling candidate in the physiological processes associated with ASD [3].

In intracellular signaling, specific signaling molecules within a cell act as chemical messengers, inducing certain physiological responses in that cell. In intracellular calcium signaling, Ca2+ ions act as the signaling molecules and are involved in critical neurological functions such as cell secretion, cell death, and excitation of nerve cells to transmit impulses [4]. Many research efforts have begun to focus on the mitochondria, a major intracellular calcium buffer that uses signaling to communicate dynamically with the endoplasmic reticulum (ER), a major calcium store within cells. This communication is particularly vital for integrating electrochemical messages with cellular metabolism in many reactions that occur within the cell [5]. Dysfunction in mitochondrial Ca2+ signaling have been implicated in autism, as well as in many other neurologic disorders such as Parkinson’s and Alzheimer’s disease [6,7].

The Gargus lab at the University of California, Irvine is composed of six researchers that are currently investigating calcium signalling in the hopes of finding ASD biomarkers (physiological properties that act as indicators of the disease). The team is a part of the Center for Autism Research and Translation (CART) and believes that the goal of CART is to “understand the causes of autism and to facilitate collaborations between researchers of multiple disciplines to allow us to take novel approaches that uniquely distinguishes our facility from other research institutions” [8]. Previously, the Gargus lab used specialized microscopy to test fibroblast cells derived from skin samples of patients who had autism due to a single defective gene. Fibroblast cells, which are commonly found in connective tissue, produce important structural fibers. The results of the study showed that the release of calcium from the ER through specific calcium channels was impaired in the tested fibroblast cells [9,10]. In a current ongoing study, the Gargus lab is now investigating whether this impaired intracellular Ca2+ signalling is also affected by a dysfunction in mitochondrial activity. Through this study, the Gargus lab hopes to find a genetic biomarker for ASD and further improve our knowledge of the mechanisms behind the disease. Rachel Nguyen, a member of the lab, was able to sit down with us and discuss the study and its significance.

Today, the team is focusing their attention on calcium ions as biologic markers for ASD. Rachel noted that “much of our recent research has pointed to a dysfunction in IP3-mediated calcium signaling as an indicator for the disorder and our findings that identified this dysfunction can be further developed into more intricate cell studies to study the exact chemical mechanisms involved in producing the physical attributes in autistic individuals” [8]. Although there is a plethora of people conducting research on autism with many different causes being looked at, the Gargus lab is one that is set apart from the rest. Unlike many labs worldwide, the Gargus lab has the unique advantage of being a part of CART and being one of the few “labs who are specifically focused on calcium signaling networks in autism” [8]. However, it is not about who finds the biomarker first, but rather about collaborative efforts with institutions and labs worldwide.

Autism is a highly complex disorder. The diversity of its physical characteristics and genetic makeup has made it extremely difficult to study and develop correlations between specific genes and how they manifest physically. However, Rachel believes that “advancements in genetic sequencing and neurotechnology may allow us to overcome many of the limitations in research that we have previously encountered” [8]. Whether it is looking into calcium signaling or finding a genetic biomarker, one thing is for certain, the combination of works from those all around the globe and their collaborative efforts are bringing the world one step closer to identifying the indicators of autism.

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