Liu D-C, Lee KY, Lizarazo S, Cook JK, and Tsai N-P.
Neurobiology of Disease, 2021
Researchers link abnormal neural activity in FXS to common cellular challenges
Imbalanced neuronal excitability homeostasis is a common abnormality in people who have fragile X syndrome (FXS)—an inherited disorder associated with intellectual disability, seizures, autism spectrum disorder, attention-deficit/hyperactivity disorder, and other health concerns—but scientists do not fully understand the role of endoplasmic reticulum (ER) stress in FXS-related seizure susceptibility. However, researchers using Fmr1 knockout (KO) neurons and animal models demonstrated that an impaired response to common cellular stress challenges may contribute to abnormal neural activity in FXS. The Fmr1 gene, which makes the FMRP protein necessary for brain development, is absent in people with FXS.
To examine neural activity, researchers used Axion’s multi-electrode array system to analyze data from primary mouse cortical neuron cultures derived from Fmr1 KO mice injected either with saline or with the ER stress inducer Thapsigargin (Tg). The results showed that Tg significantly and abnormally increased synchronization in the Fmr1 KO cultures, findings the authors suggest may help to explain seizure susceptibility in FXS. Taken with other findings from the study and given the fact that imbalanced neuronal excitability has also been linked to other conditions such as autism spectrum disorder, the researchers hope to expand their understanding of ER stress impairments and identify potential therapeutic targets.
