Tests on mice give hope for the success of lithium in treating…

The most notable discovery Lithium It is a drug that has long been used to treat bipolar disorder and depression as a potential treatment for a spectrum disorder Autism (ASD).

This research, conducted by a team at the Center for Brain Neurological Dysfunction, reveals… Institute of Basic Sciences (IBS) led by Director Kim Eun-jun, has shown that lithium can restore brain function and alleviate behavioral symptoms in animal models of autism spectrum disorder caused by mutations in the Dyrk1a gene.

Autism spectrum disorder is a neurodevelopmental disorder that affects 2.8 percent of the world’s population, and is characterized by social deficits, repetitive behaviors, intellectual challenges, and anxiety. Because autism spectrum disorder imposes a heavy burden not only on the patients themselves but on their families and society as a whole, methods must be developed Therapeutic New treatment for core symptoms of autism spectrum disorder. Despite its prevalence, there are no definitive treatments or preventive measures.

Among the many genetic risk factors for autism spectrum disorder, Dyrk1a mutations stand out as important, leading to conditions such as Dyrk1a syndrome. Patients carrying the loss-of-function Dyrk1a mutation have suffered from autism spectrum disorder, microcephaly, language problems, social impairment, and anxiety. A mouse model carrying the truncating Dyrk1a I48K mutation (mutation in a human patient) also closely mimics these phenotypes.

One of the underlying mechanisms of ASD symptoms due to Dyrk1a mutation, which was discovered within this study, is disrupted phosphorylation levels of mTOR (mammalian target of rapamycin). To find the specific substrate of Dyrk1a.

The researchers needed to generate mice that lack full expression of Dyrk1a (homozygous), a condition known to be embryonic lethal. However, by altering the genetic background of the mouse, it was possible to generate live animals carrying this mutation.

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However, the survival rate was minimal, with less than 5 percent of the mutant pups surviving. After overcoming this difficult part, the authors found that the phosphorylation levels of different elements of the mTOR pathway, and mTOR itself, were changed by the expression levels of Dyrk1a.

Accordingly, they chose lithium to address this deficit, and as a temporary therapeutic drug in mice carrying the Dyrk1a mutation. When lithium was given to mice carrying the mutation during their youth, the results were remarkable. Lithium normalized brain volume, restored the structure and function of excitatory neurons, and significantly improved anxiety-related behaviors and social interaction. Even more promising, the effects of this short-term treatment persisted into adulthood, suggesting that lithium may have long-term benefits by enabling structural and functional recovery in the brain.

Through advanced mass spectrometry analysis, the proteins and phosphorylation levels rescued by lithium in mice carrying the Dyrk1a mutation were extensively investigated. The team discovered that the therapeutic effects of lithium are mediated in part through its effect on Kalirin-7, a molecule essential for synaptic structure and function. By targeting this molecule, lithium helped restore balance in brain signaling networks, addressing one of the underlying mechanisms of autism spectrum disorder.

“This is an exciting breakthrough. Dyrk1a mutations disrupt neural communication, just like traffic jams or roadblocks in a city. Lithium helps clear congestion, restoring smooth communication between neurons,” said Dr. Roh Junyup, first researcher and co-first author of the study.

Study director Kim Eun-joon emphasized the potential impact of these findings, saying: “Our research shows that lithium, a widely used medication for bipolar disorder, can also work as a treatment for autism spectrum disorder. The fact that its effects persist long after treatment has ended confirms “The importance of early intervention during critical developmental periods.”

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