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The following is a description of our research from our researcher Dr. Alexey Pshezhetsky, Ph.D

Lay language progress report for 2016
During the year of 2016 we continued to study neurons (brain cells responsible for memory and learning) in our mouse model of Sanfilippo syndrome. Using different techniques, we were able to identify several processes that may compromise transmission of signals (impulses) between the neurons during the Sanfilippo syndrome and contribute to behavioral and cognitive problems in the patients.

The surface of the neurons has small protrusions called spines, and each neuron should have multiple spines to receive impulses from another neurons. The spines may have different shapes but the mature healthy ones that transmit strong and rapid signals look like tiny mushrooms with a distinct stem and a cap. In our analysis, we found that neurons from Sanfilippo mice lacked these mature “mushroom-like” spines and we think that this may affect how the nervous impulses are transmitted in their brain. We also discovered that many proteins that are necessary for the transmission of the impulse are either reduced in concentration or do not have a normal localization in the Sanfilippo neurons.

Each transmission of nervous impulse generates a very small and short electric current inside the neuron. Some of these currents “wake up” (excite) neurons, and some put them to sleep (potentiate). Our next goal therefore was to measure these currents in neurons from Sanfilippo and from healthy mice. We found that cells from Sanfilippo mouse have 4 times more frequent appearance of the electric current associated with excitation and we are presently working to unveil the causes and outcomes of this finding.

For the transmission of the nervous impulse, the neuron should release a chemical called neurotransmitter, which is perceived by neighboring cell and triggers the electric signal for the propagation of the impulse from neuron to neuron. These neurotransmitters are packed in small “pockets” inside the cells, called synaptic vesicles, and they are released during transition of the impulse. We used a high-resolution microscope called electron microscope to analyze the neurons, and found that those from Sanfilippo mouse have less synaptic vesicles than the healthy ones. In order to reach the site of neuronal connection synaptic vesicles need to be trafficked very quickly inside the neuron, and under normal conditions they move along a protein that resembles a rail, called microtubule. We found that these microtubules are disorganized in Sanfilippo neuron and think that this may affect the trafficking of the synaptic vesicles and explain why they are reduced. 

In the end of February 2016, the preliminary results obtained in our lab were presented as a lecture and a poster at the WORLD Symposium, a conference to discuss lysosomal diseases, that happened in San Diego (CA, USA) and we received an award (Young Investigator Award 2016) for the remarkable data about the neuropathophysiology of Sanfilippo syndrome type C. This project also rendered our lab two scholarships, one from the RMGA (Network of Applied Genetic Medicine) and the other one from FRQNT (Québec Fond for Research in Nature and Technologies) called Quebec Merit Scholarship for Foreign Students).

To make a donation.  Make a check out to JLK Sanfilippo Research Foundation and mail to the following  address.

JLK Sanfilippo Research Foundation
P.O. Box 564
Belmont, MA 02478