Summary: Lithium, a drug widely used for bipolar disorder, may also treat autism spectrum disorder ( ASD ), according to new research. In animals with Dyrk1a gene mutations, a known ASD risk factor, sodium restored mental performance and reduced behavioural signs.
Administered during the adolescent time, sodium adjusted brain size, improved neurological connectivity, and eased anxiety and cultural deficits, with benefits persisting into adulthood.
This discovery highlights the potential of lithium to address fundamental ASD mechanisms by blocking the release of Kalirin-7, a molecular essential for neural function. The results highlight the value of early detection and focused ASD treatment.
Important Information:
- Biological Goal: Lithium’s results are mediated by Kalirin-7, addressing Dyrk1a variants linked to ASD.
- Long-Term Rewards: Short-term potassium treatment in adolescents improved brain function and actions into adulthood.
- Medical Potential: The research highlights lithium as a appealing treatment for core ASD symptoms.
Origin: Institute for Basic Science
A new discovery has highlighted the potential therapy for autism spectrum disorder ( ASD ) as lithium, a medication that has been used for years to treat bipolar disorder and depression.
This study, led by Director Kim Eunjoon, is the result of a team at the Institute for Synaptic Brain Dysfunctions ‘ ( IBS ) Director’s direction. It turns out that lithium can restore brain function and lessen behavioral symptoms in animal models of ASD brought on by mutations in the Dyrk1a gene.
ASD is a developmental disorder affecting 2.8 % of the global community, characterized by social imbalances, repetitive behaviors, academic issues, and anxiety.
New medical approaches may be developed to treat the primary indicators of ASD because it places a heavy burden on both the clients themselves and on society as a whole.
Despite its occurrence, there are no clear solutions or precautionary measures.
Among the many genetic risk factors for ASD, Dyrk1a , mutations , stand out as important, leading to problems such as Dyrk1a illness. Individuals carrying Dyrk1a loss-of-function gene have presented with ASD, idiocy, language problems, social illness, and stress.
The , mouse model , carrying Dyrk1a I48K truncation mutation ( a human patient mutation ), also mimics these traits closely.
One of the underlying causes of ASD symptoms brought on by the Dyrk1a mutation was the impaired phosphorylation levels of mTOR ( a mammalian target of rapamycin ), which was discovered in this study.
The experts needed to breed mice that had homozygote, a condition known to be embryonally devastating, in order to identify the specific material of Dyrk1a.
But, by switching the mouse biological history, it was possible to generate live creatures with this mutation.
Even so, the success rate was horrible, with less than 5 % of the humanoid dogs surviving. After overcoming this challenging stage, the authors discovered that Dyrk1a appearance rates altered the phosphorylation rates of several mTOR components and mTOR itself.
Consequently, they have chosen sodium to address this gap, and as a preliminary solution drug in Dyrk1a mutated mice. The outcomes were extraordinary when lithium was administered to the mutant animals while they were still young.
Lithium normalized , mental dimensions, restored the structure and function of activating neurons, and substantially improved actions related to anxiety and social connection.
Even more appealing, the effects of this short-term care lasted into age, suggesting that lithium may include long-term benefits by enabling architectural and efficient recovery in the brain.
In mice with Dyrk1a gene mice, extensive mass spectroscopy was used to screen the proteins and their kinase levels that were recovered from lithium.
The research found that lithium’s healing effects are largely mediated by its interaction with Kalirin-7, a molecular essential for neural structure and function.
By targeting this protein, sodium helped to restore stability in the body’s signaling networks, addressing one of the primary systems of ASD.
” This is an interesting breakthrough”, said Dr. Roh Junyeop, a senior researcher and co-first author of the study.
” Dyrk1a mutations destroy neurological connectivity, much like a traffic jam or obstacles in a town. Lithium helps to clean the gridlock, restoring smooth connection between cells”.
Director Kim Eunjoon emphasized the potential effects of these observations, stating,” Our studies shows that , lithium, a commonly used medication for , bipolar disorder, may also function as a cure for ASD. The importance of early intervention during critical developmental periods is highlighted by the fact that its effects continue long after treatment ends.
This study,  , published , in the journal , Molecular Psychiatry , on December 5, not only paves the way for new therapeutic approaches for ASD but also underscores the critical importance of early diagnosis and intervention.
It offers hope to ASD-related families and individuals, suggesting that targeted treatments may one day lessen the burden of this complex disorder.
About this research in autism and psychopharmacology
Author: Kim Eunjoon
Source: Institute for Basic Science
Contact: Kim Eunjoon – Institute for Basic Science
Image: The image is credited to Neuroscience News
Original Research: Open access.
” Lithium normalizes ASD-related neuronal, synaptic, and behavioral phenotypes in DYRK1A-knockin mice” by Kim Eunjoon et al. Molecular Psychiatry
Abstract
Lithium normalizes ASD-related neuronal, synaptic, and behavioral phenotypes in DYRK1A-knockin mice
Dyrk1A deficiency is linked to various neurodevelopmental disorders, including developmental delays, intellectual disability ( ID ) and autism spectrum disorders ( ASD ). Haploinsufficiency of , Dyrk1a , in mice reportedly leads to ASD-related phenotypes.
However, the key pathological mechanisms remain unclear and human , DYRK1A , mutations remain uncharacterized in mice.
Here, we generated and studied , Dyrk1a-knockin mice carrying a human ASD patient mutation ( Ile48LysfsX2, Dyrk1a-I48K mice ).
These mice display severe microcephaly, social and cognitive deficits, dendritic shrinkage, excitatory synaptic deficits, and altered phospho-proteomic patterns enriched for multiple signaling pathways and synaptic proteins.
Early chronic lithium treatment of newborn mutant mice rescues the brain volume, behavior, dendritic, synaptic, and signaling/synapse phospho-proteomic phenotypes at juvenile and adult stages.
These findings support the hypothesis that early lithium treatment can prevent both juvenile and adult-stage phenotypes contribute to the phenotypic changes observed in Dyrk1a-I48K mice.
