October 16, 2021

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by: admin

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Tags: Autism, brain, improves, memory, models, mouse, Spectrum, stimulation

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Categories: autism

Mind stimulation improves reminiscence in autism mouse fashions | Spectrum

Brain Boost: Electrical stimulation of the fornix weakened abnormal inhibitory signals in mice with CDKL5 mutations and restored their performance in learning and memory tasks.

Manjurul / iStock

Chronic electrical stimulation of the fornix, a bundle of nerve fibers deep in the brain, saves learning and memory deficits in mice with mutations in the autism-linked CDKL5 gene, according to new research.

The results support previous work in mice, which suggests that electrical shocks in this fiber tract that connects brain regions involved in memory could help address cognitive problems in several models of neurodevelopmental disorders. These animal studies all use deep brain stimulation (DBS), which involves placing electrodes chronically, or in some cases permanently, in specific neuroanatomical regions.

In humans, severe cognitive impairment, including memory and learning deficits, is a central feature of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder, which results from mutations that impair the production of the CDKL5 protein. Other characteristics include signs of autism and epileptic seizures.

“Our hope is to help patients with CDKL5 deficiency with at least some aspects of their problems – such as intellectual disabilities,” says lead researcher Jianrong Tang, associate professor of pediatrics at Baylor College of Medicine in Houston, Texas.

Hit the hippocampus:

Little is known about how the loss of CDKL5 affects brain circuitry. In the new study, Tang and his colleagues analyzed the brain’s memory center, the hippocampus, in mice with CDKL5 mutations. The connections between the neurons there were less flexible, which likely contributed to the animals’ learning and memory deficits. The mutations also increased the inhibitory signals in the dentate gyrus, a part of the hippocampus that helps make new memories.

DBS stimulation of the fornix for one hour per day for two weeks attenuated the abnormal inhibitory signaling. It also restored the animals’ ability to perform learning and memory tasks: three weeks after the stimulation, treated mice were more likely than untreated to remember the circumstances in which they received an unpleasant but harmless electric shock to their feet.

Injecting a drug that blocks neuronal inhibition called gabazine directly into the dentate gyrus also improved performance on this task. This suggests that pharmaceutical or gene therapies that target this brain circuit might be worth investigating for treating humans, Tang says. The work was published in the Journal of Neuroscience in September.

Previously, Tang and colleagues found that DBS targeting the fornix could improve learning and memory deficits in a mouse model of Rett syndrome, another condition associated with autism.

The fact that stimulating the fornix can correct learning and memory deficits in two different mouse models suggests that the approach could be applicable to more than one human disease, says Jacque Pak Kan Ip, assistant professor of biomedical sciences at the Chinese University of Hong Kong. who was not involved in this work. “I find this study very encouraging.”

But before this research can find clinical applications, more questions need to be answered.

For one, it’s unclear whether the improvements documented in this study are permanent, says Joe Zhou, a professor of genetics at the University of Pennsylvania who was not involved in the study. Further testing in animal models should address these concerns.

Future work should also identify the best time to apply stimulation, says Ip. “If it were to be used in adults, would that be too late and would it limit the effect? Or should it be used as young as possible to maximize the impact? “

If so, scientists need to determine whether DBS, an invasive technique that requires brain surgery, is safe in children and whether it could interfere with other aspects of development, Ip says.

Quote this article: https://doi.org/10.53053/QDKR1080

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