GENETIC MEMORY

GENETIC MEMORYIt is always a challenge to be asked to give a presentation to a group of individuals about a topic to capture their attention, stimulate their interest, and spark their imagination. Eugenics and cloning have been topics of science fiction for years, however, today the topics beong in the area of regulation and ethics of reality for science and that science is not fiction.

Cross Sectional Cut.

What I would like to discuss with you is some genetic research that has been ocurring over the last 12 years. Carried out at Cornell, Columbia, the National Institute of Health, and the University of Hong Kong. Doctors Barbara Hemstead, Co-Chief of the Division ofHematology/Oncology in the department of medicine of Cornell. Dr. Bai Lu of NIH, Dr. Petti Pang, PhD., of the University of Hong Kong. Dr. Duane Alexander of NIH, and Eric Kandel of Columbia University.

GENETIC MEMORY

GENETIC MEMORY

What these researchers have deicated the last 12 years of their research to is the study of memory and the proteins involved in the making of short term to long term memory. The end result would be to try and eradicate learning disablities and try to alleviate the mental deterioration of Alzheimers Disease.

GENETIC MEMORY

As quick over-view we know how memories are made we understand how the proteins and enzymes interact with the processing of memories. If you will recallthe portion of the brain linked to memory is the Hippocampus. By sacrificing rodents and placing electrodes in the Hippocampal slices then discerning which proteins were present or absent dictated to us the responsible proteins for memory.

GENETIC MEMORY

A single protein known as mBDNF (Mature Brain Derived Neurotrophic Factor) chemically alters neurons boosting their ability to communicate with one another.

GENETIC MEMORYLeft Temporal view.

HippocampusTemporal cross section cut.

GENETIC MEMORY The portion of the brain that helps those names get into memory in the first place, this Hippocampus we are talking about, is also part of this temporal lobe. But you can't see it here, because it's an inside fold, not these outside folds you see above. To see the Hippocampus we'll have to use x-ray vision. Imagine you could just squint and see right through the temporal lobe to what's underneath.

GENETIC MEMORY

In 1996 it was discovered BDNF fostered changes in cells indicative of memory. In 1998 Nobel Laureate Dr. Eric Kandel reported that TPA, (Tissue Plasminogen Activator) was also involved in long term memory.

GENETIC MEMORY

A breakthrough in 2001 with Dr. Barbars Hepstead, MD, PhD. Deciphered the chemical reaction leading to the formation of mBDNF, researchers relied on observations of laboratory phenomenon thought to mirror changes that occur in the brain when long term memory is formed.

GENETIC MEMORY

Neurons communicate via a relay system of electrical impulses and specialized neurotransmitters are released which bind to reeceptors on nearby neurons. The recipient neurons then generate their own electrical impulses and release their own neurotransmitters. When long term memory is made researchers believe that neurons gain the capability to transmit a much stronger electrical impulse than they otherwise would and thus require much less neurotransmitter.

GENETIC MEMORY

Brain Neurons synapsing with one another and communicating via axons.

GENETIC MEMORY

In the first of the experiments NIH researchers found that treating Hippocampal slices with a compound that prevents new proteins from being made. Researchers found that protein synthesis for the formation of long term memory. As expected applying current to the brain slices failed to bring about LTM because mBDNF could not be manufactured.

Researchers then applied mBDNF directly to the Hippocampal slices before applying current. They found that mBDNF completely restored long term potential. This demonstrated that mBDNF was essential to memory formation and that mBDNF was the new protein that Scientist had been searching for that underlies the long term potential of long term memory.

GENETIC MEMORY

In the second of the experiment series Scientist at NIH tested Hippocampal slices that were genetically incapable of producing the protein and enzyme needed to produce mBDNF. As a result the researchers could not induce the long term potential for long term memory. However, they could induce the LTP in the brain slices if they first supplied the slices with mBDNF. Researchers also discovered that mBDNF could restore long term potential in brain slices incapable of producing plasminogen.

GENETIC MEMORY

Next the researchers treated plasminogen deficient brain slices with a form of proBDNF that could not be converted to mBDNF, once again long term potential could not be induced.These experiments showed that both plasminogen and TPA are needed to bring about long term memory potential for the production of mBDNF.

Entire chemical sequence by which TPA brings about the formation of mBDNF:http://www.nichd.nih.gov/new/releases/conversion_model_image.cfm

GENETIC MEMORY

In 2005 Y. Peng Loh, PhD. of NICHD, (National Institute of Child Health and Human Development) head of cellular neurobiology research was published. Specifically this research discovered the enzyme carboxypeptidase E (CPE), is needed to deliver the early or inactive BDNF--proBDNF to a special compartment in the neuron. Once in the neuron compartment the pro form is converted to the active form mBDNF. Once formed it is released to the outside of the cell where it binds to receptors on other neurons to form LTM.

GENETIC MEMORY

Dr. Loh explained like other proteins proBDNF is made inside the endoplasmic reticulum there it travels to the golgi apparatus. Here the proBDNF binds to the CPE which protrudes from molecules of lipid. If this process does not occur pro cannot become mature or active BDNF. These lipid vesicles travel to the outer membrane where mBDNF is then released.

GENETIC MEMORY

Dr. Loh noted that rodents that were deficient or genetically incapable of producing CPE could not deliver mBDNF. mBDNF was not made because the pro form was never delivered to the vesicles. Instead it leaked out of the golgi apparatus; because the mice could not make mBDNF the mice were shown to have poor LTM.

GENETIC MEMORY

Do you see what this means? A product in the very near future could be called "Memory in a Bottle."

GENETIC MEMORY

What are we outside of our physical bodies? We are a collection of thoughts, ideas, concepts, all encompassing and making memories. Is it such a leap in thinking to believe that one day science and medicine can extract the patients memories and place them in an artificial environment. In a bottle if you will. To be able to do this would enable the individual to not only prevent memory loss and increase learning capacity but it would in reality have the person living forever. Thank you. Aaron Cusimano, MD