Impaired Recycling Of Mitochondria Could Be Responsible For Autism

Defects in autophagy of mitochondria have been implicated in a number of neurological disorders such as autism, Parkinson's disease and Alzheimer's disease.

Tuberous sclerosis complex (TSC), a genetic disorder that causes autism in about half of those affected, could stem from a defect in a basic system cells use to recycle their mitochondria, report scientists at Boston Children's Hospital.

Defects in mitophagy, or autophagy of mitochondria, have already been implicated in a number of neurological disorders such as Parkinson's disease and Alzheimer's disease. The scientists believe their findings open new treatment possibilities not just for TSC, but possibly for other forms of autism and some neurological disorders.

Autism Causes, Symptoms, Diagnosis, Treatment, Prognosis
Autism is a neurodevelopmental disorder typically characterized by impaired social and communication skills combined with repetitive movements.

‘Developing treatments that counter the defects in autophagy of mitochondria could be a therapeutic target for TSC, and may also have implications for other neurological diseases that involve mitochondrial dysfunction.’

Mitochondria, the organelles responsible for cellular energy production and metabolism, constantly get recycled. Through a process known as autophagy ("self-eating"), cells literally digest their damaged or aging mitochondria, clearing the way for healthy replacements.

The new study, led by Mustafa Sahin, MD, PhD, and co-first authors Darius Ebrahimi-Fakhari, MD, PhD, a resident at Boston Children's Hospital, and medical student Afshin Saffari, in Boston Children's F.M. Kirby Neurobiology Center ,is published online October 18 by Cell Reports.

"We decided to use tuberous sclerosis, a genetically defined disorder that has a high incidence of autism, as a model to understand the role of mitochondrial dynamics," says Sahin.

Diabetes Drug Metformin Decreases Weight Gain in Children With Autism
Young people with autism are given antipsychotic medications that are likely to increase weight. A new study claims that metformin could counteract the side effect.

Sahin, Ebrahimi-Fakhari and colleagues studied both rat neurons and patient-derived neurons affected by TSC and used live-cell imaging to examine the distribution and dynamics of mitochondria.

They found that the TSC neurons as a whole had more mitochondria, and in particular more fragmented and dysfunctional mitochondria. It shows that autophagy is defective in TSC.

Lack Of Evidence To Recommend Screening All Children For Autism: US Task Force
The rate of autism has risen since 2000 when one in 150 children were diagnosed with the disorder which can involve difficulty in social settings and learning abilities.

The scientists further showed that two existing classes of drugs counter the defect: the epilepsy drug carbamazepine, and drugs known as mTOR inhibitors.

When treated, the dysfunctional neurons were able to clear damaged mitochondria and replenish healthy mitochondria, restoring a normal turnover.The mitochondria were replenished at presynaptic sites, where their presence is most critical.

Quiz on Autism
Autism spectrum disorder is a complex genetic disorder that impairs social, behavioral, and communication functions in humans. Autistic people may act, communicate, interact, and learn differently than most other people. ASD usually begins in childhood and can last for the rest of a person's life, though symptoms may improve over time

"Our findings point to possible treatments for enhancing mitophagy for some neurodevelopmental and neurodegenerative diseases," says Sahin, who is also director of the Translational Neuroscience Center at Boston Children's and senior author on the paper.

Source-Medindia