Autism-related research in Drs. Baudry and Bi Laboratories
- Mechanisms implicated in long-term synaptic potentiation and depression in hippocampus and other brain regions
- Regulation of glutamate receptors
- Role of oxygen free radicals in central nervous system
- Mechanisms underlying selective neuronal degeneration
- Computational neuroscience
Research in my laboratory seeks to understand how neurons develop, mature, and function properly and how they die when challenged by natural aging process, by intrinsic genetic defects, or by various insults. We hope that by understanding the basic molecular and cellular mechanisms that govern these processes we can develop better preventive and therapeutic strategies for central nervous system disorders in children as well as in elders.
Drs. Baudry & Bi Laboratories is interested in understanding the molecular/cellular mechanisms underlying synaptic plasticity, which is the ability of the contacts between nerve cells to be modified by experience, and which forms the basis for learning and memory as well as for many cognitive processes. It is clear that this process is abnormal in autism and scientists have been searching for the cause or causes of these abnormalities. In particular, it is now apparent that many genes coding for proteins participating in synaptic plasticity are mutated in children with autism. Scientists can use these mutations to generate mice models of the disease, and mice exhibiting the same mutations as the humans affected by these mutations appear to have some of the symptoms of the autistic children. We are interested in understanding how the balance between protein synthesis, protein degradation and the mechanisms involved in protein quality control are modified during postnatal development in various models of neurodevelopmental disorders. In particular, we are studying one mouse model of a rare neurodevelopmental disease, the Angelman Syndrome. About 30% of Angelman patients are co-diagnosed with Autism.
Features of Angelman Syndrome include:
- Severe developmental delay
- Language and cognitive deficits
- Motor disorders
Angelman Syndrome is caused by maternal deletion of chromosome 15q11-q13. Interestingly, duplication of this region is a high risk factor for Autism. We are using a mouse model to understand the mechanisms underlying the abnormalities in neural connectivity that take place during postnatal development. We are making cultures of the neurons from different brain regions, such as the hippocampus, a brain structure particularly important for learning and memory, and cortex, a brain structure important for cognition, to discover the protein expression and the brain circults that are altered in Angelman Syndrome.
While we do know the particular mutation, and the nature of the protein which is modified, we do not understand why this mutation produces impairment in synaptic plasticity. Although we don’t know the mechanisms underlying the alterations in synaptic plasticity, we were recently able to reverse them by a short treatment of the mice with a drug, which had been previously shown to improve synaptic plasticity in another model of autistic syndrome, the Fragile X mice. This drug is called an ampakine, and it facilitates the functioning of a receptor for a neurotransmitter involved in synaptic plasticity. We were able to show that after 4 days of treatment with the drugs, synaptic plasticity in hippocampal slices was returned to the same levels found in the control mice, and the learning of a task requiring normal hippocampal function was also returned to the levels found in the control mice.
These findings give us hope that, despite the numerous causes underlying the various forms of autistic syndrome, it is possible to use drugs and potentially other manipulations, such as demonstrated by our colleagues at WesternU, to reverse the abnormalities found in children and even in adults.
See Drs. Baudry and Bi discuss their important work on Autism Intersection, coming soon to theautismchannel.tv
Douglas Ethell, PhD
Associate Professor, Head of Molecular Neuribiology Group
Graduate College of Biomedical Sciences & BMS, College of
Osteopathic Medicine of the Pacific
My research interests are focused on neurodegenerative disorders, specifically Alzheimer’s disease and Parkinson’s desease. Experimental systems we use include transgenic mice, cell and molecular biology, as well as human tissue samples. Recently, I have established stem cell techniques in my lab that allow us to produce neurons and immune cells from induced-pluripotent stem cells. My research has been supported by grants from NIH and the National Multiple Sclerosis Society, with current funding from the California Institute for Regenerative Medicine (CIRM) and the FRAXA Foundation.