Wednesday, September 19, 2012

Key Molecules involved in forming long-term Memories

We are not moving at this time although you can find us in both places here and at make sure you check out both sites. In this article it says they have found the molecules that form long-term memories. It can help with Schizophrenia and Alzheimer’s. “There are many drugs available to treat some of the symptoms of diseases like schizophrenia… ‘but they don’t treat the cognitive deficits that patients have, which can include difficulties with memory. This study looks for more specific targets to treat deficits in cognition.” If you read in the internet about people with schizophrenia it is clear that they have cognitive problems. Memory is one of them. It would help people with schizophrenia find jobs and just have a better life if they can make drugs that could help.
The article says: “… the study focused on a group of proteins called nuclear receptors, which have been implicated in the regulation of a variety of biological functions, including memory formation. Nuclear receptors are a kind of transcription factor, proteins that can bind to DNA and regulate the activity of other genes. Their regulatory role may be significant in memory formation, as a gene transcription is required to turn short-term memories into long-term lasting ones by strengthening neuronal synapses in the brain.” These receptors are responsible for regulating functions which in turn has an impact on memory formation. Somehow these must not work in people with schizophrenia and Alzheimer’s.
To identify how this work they used trained mice. “…using a common method to create memories of a place and event, in which animals learn to associate a particular context or a certain tone with a specific experience. Associations with a place or context are believed to be encoded in the hippocampus, while memories associated with a cue such as a tone are believed to be encoded in the amygdala.” A tone would bring up a certain thing that the mice had been to or done before. “In the 24 hours after exposing the mice to the initial training, the researchers examined expression patterns of all 49 nuclear receptor genes. They found 13 that increased in expression in the hippocampus in the first two hours after training. Included in this group were all three members of a class of nuclear receptors called Nr4a. Nr4a genes had previously been found to increase in expression upon use of a memory-enhancing class of drugs called histone deacetlylase inhibitors, HSDAC inhibitors. They were able to find the genes that work on memory.
The article goes on to talk about how they were able to do this: “The scientists next created a transgenic mouse in which they could selectively block the activity of the three Nr4a genes. Having the transgenic mouse is very useful… ‘We can manipulate it so that Nr4a genes will only function in certain brain regions and then see how the mouse memory-forming ability is affected. When the researchers exposed the mice to the training context a second time, they found that the transgenic mice had reduced memory of the location where the training tool place-memories that are located in the hippocampus- compared to normal mice. In contrast, the mutant mice’s amygdala-associated memories of cue- the tone played during training remained intact. The mice had impairment for contextual memory, which means something in the hippocampus is affected… ‘That is the type of memory that goes away in Alzheimer’s and schizophrenia.” They found where and how this is affects memory. Hopefully their research can lead to better drugs for both diseases. The researchers also found out that the mice’s short-term memory was not affected.
The last part of the article says: “In addition, the scientists confirmed that Nr4a genes play a role in long-term memory storage by injecting the Nr4a-deficient mice with HDAC inhibitors, which have been shown to enhance memory in normal mice. The treatment did not enhance the memory-forming ability of the mutant mice, suggesting that the drug acts upon the Nr4a genes to boost long-term memory storage. Finally, the researchers screened mice for molecules that act ‘downstream’ of Nr4a and could be part of the signaling cascade by which those nuclear receptors help create long-term memories. They found two genes, Fosl2 and Bdnf1, that appeared to be downstream targets of Nr4a genes and also increased in expression following treatment with HDAC inhibitor.” When all is said and done they found the targets that could help bring new drugs to help people. They do not say if they will need more research or if what they found can help enough. I like when they can find new things to enhance memory.
I wrote about this it is because memory to me is very important. It is one thing I do not want to lose later in life. I started back on the memory program and today I did an assessment on the computer and scored better than the last time I did an assessment. I can remember numbers like a phone number or any set of numbers. Although I cannot remember math, my tutor when I was in college would say he remembers how to do the problems, although when he comes back the next morning it is all gone. I do not remember hardly any of my childhood except things or days that stood out. I know the math is because of my schizophrenia, because in high school and earlier I was good in math. So something happened.

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