June 2008 Issue

The Riverbend Down Syndrome Association is a 501(c)(3) non-profit organization and can receive tax deductible contributions. Our Employer Identification Number is: 14-1982424.

Laura Barnard is looking for playmates for her daughter Sierra, age 8, who has 3 brothers. Laura is looking for primarily girls from 5 to 10 years of age, residing in the Edwardsville area: e.g., Troy, Maryville, Glen Carbon, etc.

We are continually striving to include all families with a child with DS in the Madison and St. Clair counties in our newsletter mailing list. Currently we mail our newsletter to 150 families. Please advise if you know of a family who does not receive our newsletter. All back issues are posted on our website.

We have received from the publisher a copy of the book, "Life Story — The Book of Life Goes On: TV's First and Best Family Show of Challenge" by Herbie J. Pilato. Please advise if you would like to review this book for our newsletter. See: http://bearmanormedia.bizland.com/id166.html.

Local Events

July 21-25, Springfield, IL. Lose the Training Wheels™ bike camp sponsored by the Lincoln Land Down Syndrome Society, URL: www.lldss.com at the Franklin P. Nelson Center, 1601 N. 5th St., Springfield, IL. (217) 753-2800. Contact: Steve Graben, (217) 553-0767, E-mail: lldss@lldss.com.

July 31, 3:00 - 6:30 p.m. Shop'N Save/Special Olympics Night at the Gateway Grizzlies. Sauget, GCS Ballpark. Game time - 7:05 p.m.
Celebrate Special Olympics' 40th Anniversary with a night at the ballpark with the Gateway Grizzlies. Prior to the game, join us in the Grizzly parking lot for a tailgate picnic. Food, music and soda will be available. All proceeds from tickets purchased from Special Olympics Illinois will directly benefit our athletes. Tickets and/or information: Special Olympics Southwestern Area 12: (618) 654-6680, fax (618) 654-1139, E-mail: mtoennies@soill.org or sstover@soill.org.
blank.gif  September 7, 2008 1:00 p.m. Walk in the Park at Busch Stadium – Cardinals vs. Marlins. Pep Rally starts at 10:30 a.m. The St. Louis Walk in the Park will take place to: celebrate the lives and accomplishments of people with Down syndrome in our area; broaden awareness throughout our community; foster positive attitudes of all people with Down syndrome; and enjoy a fun day with family, friends, the Cardinals and local supporters.
The 2008 Walk in the Park will be a phenomenal opportunity for all the DSAGSL members, families and friends to join forces, yet again, in a picture perfect day at Busch Stadium. You can earn a free ticket to this event by raising $100 in sponsorships for the DSAGSL.

September 26. Puttin' for Down Syndrome, 4th Annual Charity Golf Tournament and Silent Auction. Clinton Hill Golf Course, 3700 Old Collinsville Road, Swansea IL, 62226, (618) 277-3700. Golf clinic for individuals with Down syndrome will be held from 3-4 p.m. Proceeds benefit St. Louis Children's Hospital Down Syndrome Clinic and the DSAGSL. For information or to register call Tim Nienhaus (618) 236-1850, (618) 799-8515 or E-mail: puttinfordownsyndrome@yahoo.com

Down Syndrome Articles

Graduation: The Writing of a Success Story by Laura Watts, M. Ed., Program Director, E-mail: LauraW@hope-haven.org, At The Center, A publication of The Down Syndrome Center, Fall 2007, p. 1 & x.

On May 22, 2007, Jonathan graduated from Sandalwood High School. He marched in to Pomp and Circumstances — student number 421 in a class of 848 — and sat with his peers in folding chairs on the floor of the Jacksonville Veteran's Memorial Stadium. Dead center. No assistance. Complete with annoying tassel, roomy blue gown, uncomfortable black dress shoes and strangulating tie.

moonlight is the newsletter of the Riverbend Down Syndrome Association.

Editor: Victor Bishop
Web Site: http://www.riverbendds.org/

And when his name was called, he walked calmly and proudly up the steps and onto the stage as 847 students suddenly stood and cheered. He turned to the audience, gave them a "two thumbs up" with the slight twist of the hips known to be his signature move and brought down the rest of the house. For a brief moment, the world stopped to recognize just one unique person.

I do not believe Jonathan's peers cheered because he had achieved unheard of academic success. He had not. He continues to struggle with basic reading, writing and math. I do not believe they cheered because he had learned to "blend in" with his non disabled peers. He had not. He is a whole foot shorter, speaks his own language and bops through the halls to the music in his head with a huge smile. I believe they cheered because they liked him. And they liked him because he was different.

Jonathan Watts

This is Jonathan's success story. But it is not the one we wrote for him when his life began.

My husband is a financial whiz. And I am an educator. Jonathan was supposed to be the King of Academics. We brought him up on that path — early literacy, therapies, tutors, labels in the home, labels in the car, labels on our bodies. We counted everything — groceries, toys, pennies and pets. We took him everywhere, made him do everything and praised his every effort. But as he went through his preschool years it was clear that he was different. Not just different from his neighborhood peers, but different from his peers with Down syndrome. He was one of the original participants in Hope Haven's Individualized Computer Instruction for Children with Down Syndrome — and the only one to hate it. He did not like to listen to stories, identify letters and words or eat sitting down. At Down Syndrome Association meetings the child care provider assigned to him was the only one that resembled a hurricane survivor when the evening was over. His teachers tried to tell me there might be "other issues" but I tried not to listen. Then one morning when he was 6 years old we found him outside in the front yard at 8 am on a Saturday morning singing while sweeping (with a broom) the leaves off the lawn, dressed in sheer pantyhose pulled up to his armpits, Dad's yard goggles and a scarf around his neck. It was clearly time to write a new success story.

Despite all our efforts to identify a winning combination of medications and behavior plans, Jonathan's school years were filled with reading and math struggles, high energy learning and exhausted family members. Middle school was scary — not for him, but for us, as he battled his way through the halls with 1600 emotionally charged typically developing pre teens. But he loved going to school and clearly stated that his favorite subject was "my friends". Because of his size, spontaneity and inability to remain on task, we felt his needs were best met in an exceptional education classroom and we were delighted to see steady — but slow — progress in academic areas. But when a decision regarding high school needed to be made, Jonathan chose the biggest and most diverse school in the city. And he chose inclusion. Lots of it. The first years were great — he showed amazing self confidence and his academics continued to progress. But in his senior year challenges arose — class periods were changed to block schedules with 90 minutes per class and class size hovered around 100. We continued to search for his success story, distracted by the fears that prevented us from realizing that he had already written it.

Jonathan's success story may not be one that makes national headlines or puts him in the Guinness book of Down Syndrome Records. But we still meet teens in the community who will slap Jonathan on the back, address him by name and tell him they go to Sandalwood. He beams with pride, returns the slap and replies with the expected Cool Teen Code (Hey, dude! How's it going?). And when they leave, confides that he does not have a clue who they are. He is thrilled with his success story — the one he wrote for himself and made happen. The one that was so much better than the one we had planned.

As we raise our children we must remember that the early years are crucial. We need to prepare them for learning, but possibly even more important, we need to build their attitudes and give them the tools to write their own stories in their own ways and in their own time. All of our children have success stories. Let us encourage our children to discover stories that focus not only on what they can do, but on who they are.

Teaching Those with Down Syndrome by Vince Schmidt (Co-Founder of the Jensen-Schmidt Tennis Academy for Down Syndrome). From Manual for Teaching Adaptive Tennis, Chapter 3, p. 9-10. United States Tennis Association. © 2006 by the United States Tennis Association, Inc. All rights reserved.

Professional tennis instructors/coaches approach each new player they are charged with teaching as an individual. Each player has his individual strengths and areas needing improvement. Children and young adults who have Down syndrome are a special population market that teaching professionals are equipped to coach through to success as well, although you may not realize you have the skills.

There are a few things to remember when teaching children and young adults with Down syndrome.

First, the concept of "softer and slower," which means to feed a ball with less pace and/or with less movement required to hit it, is fundamentally flawed. Clearly this methodology is condescending to the player and dulling to the instructor, and as a result, no one wins. It is more important to realize that if a teaching professional has an awareness of the player's complete abilities (physical and cognitive), there is no skill that cannot be taught with a tweak or two as needed. Instructors should to be willing to take some risks and to go beyond the norm to get to the desired end. Remember if it is foot placement or hand movement that you are teaching, it can be done without a racquet and ball.

Unconventional teaching aids might be just the ticket to success with a special needs student or group. At the Jensen-Schmidt Tennis Academy for Down Syndrome, run-of-the mill teaching aids are used to get concepts across. For instance, you might never think of feeding with a 4- or 5-inch playground ball. We have found that these red balls are just the ticket to allow players with Down syndrome to see how it feels to hit a forehand or backhand. A Frisbee is a perfect tool for teaching proper form on a backhand. Think about the wrist alignment and level swing needed to throw a Frisbee properly. Beach balls, which are to be kept aloft, are a great tool for teaching younger players with little arm strength. They are also a great teaching tool for older players to help them develop the short stroke for a volley. Be creative, have fun, and watch the results.

Second, there are also physical concerns when teaching children and young adults with Down syndrome. Some of the most predominant concerns that instructors face are the balance and eye/hand or foot/eye coordination difficulties Down syndrome children have. These issues are not deal breakers, but must be addressed for real instruction to take hold.

Use the same red balls previously mentioned to work on foot speed, coordination, and balance. Foot taps, "soccer dribbling" on the lines, and bounce/catching are critical drills to develop the entire player. Make drills up... we do. Use the red balls and a racquet to play "hockey." Keep players focused on controlling the ball while controlling their bodies, all the while keeping the balls inside a desired box on the court. Drop the racquets and use just your feet... you now have soccer. While hockey develops hand/eye coordination, the soccer variant develops a strong sense of working foot/eye coordination. To take it up a notch, have the players control their ball while trying to knock their opponent's ball out of the box.

Another issue with Down syndrome athletes is the all too real problem of heart defects. Whereas twenty years ago this was a limiting factor to persons with Down syndrome, in recent years many children with heart defects have had them surgically repaired. Therefore a heart condition should not preclude a player from instruction, but it must be identified for everyone's safety. Attention must be given to the duration of drill(s) and the environmental conditions, such as heat and humidity.

A condition found in players with Down syndrome is that of low muscle tone. If a player comes to an instructor with low tone, the physicality of a drill is multiplied many times over. There is no blanket answer to what the multiplier is, but suffice it to say that a player with low muscle tone works harder to perform the same movement as a player without a low muscle tone issue.

Never discount a shortness of attention, a serious concern for a player with Down syndrome. I am not describing Attention Deficit Disorder (ADD), but rather the short attention span, which is sometimes a symptom of the disease itself Down syndrome. Other times it is the result of an athlete doing activities or programming which are beyond the normal scope of his/her "usual" daily activities. Many of the players who come out for tennis might be "first-timers" with a sport that requires as much attention to detail as tennis does. Therefore, it is safe to assume that your expectations of what it takes to do a drill and what a Down syndrome player's reality is might be vastly different. Again, this ought not to be a deal breaker for teaching a player with Down syndrome, but a call to the instructor to use a varied approach with multiple drill changes for the desired skill.

The ultimate key to teaching Down syndrome players is FUN. No one feels satisfied if a lesson is like pulling teeth. From the Grand Slams to the public parks, the best drills, lessons, programs, and players are those that are comfortable, challenging, and fun. It should be no different just because a player is a member of a special population. You might have to mix up your routine a bit more, take a few more breaks, and think and approach your day from a different perspective. As a teaching professional, these are the kind of lessons that make us think more creatively and be more flexible. Working with players with Down syndrome makes me a better instructor across the board. If you work with Adaptive Tennis, you will gain just as much, maybe more, than the players you are gifted to work with. Enjoy!

Life lessons of parenting by Gregg Rogers, E-Mail: ccdssociety@gmail.com. Centre Daily Times, Centre Living B1. 'This I Believe': Local Viewpoints. Sunday, Apr. 20, 2008.
Gregg Rogers [...] says his daughter Genevieve, who has Down Syndrome, has taught him a lot about life. He's joined by his daughter Emily, his son Ben and his wife, Lucy. Rogers has another daughter, Cecilia, who was out of town.

The doctor was talking about my unborn daughter and the results of an amniocentesis test. I know she said something else after that statement, but I don't remember what.

I do remember returning home with my wife and crying on the sofa. I distinctly remember saying "I don't want this."

I didn't want this situation. I didn't want this responsibility. I didn't want to become one of those parents - the parent of a child with a disability.

Rogers Family.

A friend told me, "If anyone can handle it, you can."

"Easy for you to say," I thought. "God never gives you more than you can handle," another friend reassured me.

"Really? Then why do people have nervous breakdowns?"

"We'll help however we can," the neighbors said.

"Fine," I thought. "You have the kid with the developmental delay, and I'll help YOU out."

For months I was terrified. I now refer to the period of time after we received the diagnosis as "The Pit." I barely spoke to my wife, Lucy, because I didn't know what to say. I simply suffered through each day. Lucy and I were together, but I felt terribly alone.

And then Genevieve was born. She went directly by helicopter to the neonatal intensive care unit at Janet Weis Children's Hospital in Danville because she couldn't figure out how to breathe. I spent eight straight days making the 150-mile round trip to see her. I sat, amidst the beeping and blinking lights, wearing a surgical gown, holding her in a tangle of tubes and wires, singing the same songs I had sung to our other daughters. On the ninth day, she came home.

Soon, we'll celebrate Genevieve's third birthday. She walks and she runs and she climbs on everything. She loves to wrestle with her 2-year-old brother, Ben. She doesn't say a lot of words, although her first full sentence was, "What's up with that?" She does have over 100 signs that let her to ask for strawberries, pizza, or ice cream, or tell us when she wants to sleep, or play on her computer. She smiles all the time and attracts admiring strangers in a way I've never seen before. She knows more people at the supermarket than I do. I laugh every day because of Genevieve.

I believe Genevieve is here for everyone. I believe Genevieve is taking over the world, one heart at a time. I believe that what was once my perceived damnation has become my smiling salvation.

On my right wrist, I wear a simple silver chain with three little beads. I used to say the three beads signified the third chromosome that results in Trisomy 21. Now, when I look at those beads, they remind me to believe in the value of all human beings. They also remind me that I don't know as much as I think I do, but I'm capable of more than I think I am.

Gregg Rogers, of Patton Township, is a senior lecturer in the English Department at Penn State and is president and co-founder of the newly formed Centre County Down Syndrome Society. For more information on the organization, visit www.centrecountydownsyndrome.org.

SMFM: Learning Deficit Blocked in Mouse Model of Down's by Charles Bankhead, Staff Writer, MedPage Today. Published: February 04, 2008. Reviewed by Zalman S. Agus, MD; Emeritus Professor, University of Pennsylvania School of Medicine. Reprint permission granted by Kristina Fiore, Proofreader/Production Editor. © Copyright MedPage Today, LLC. All Rights Reserved. URL: http://www.medpagetoday.com

DALLAS, Feb. 4 – The learning deficits of mice with trisomy 21 appear to have been prevented with a peptide combination, investigators said here.

After nine days of treatment, adult mice with the model of Down's syndrome navigated a water maze test as easily as a control group of animals and significantly better (P<0.001) than untreated trisomic mice, reported Catherine Spong, M.D., of the National Institute of Child Health and Human Development.

Ten days after stopping the peptide treatment, the water maze performance of treated animals had deteriorated to the level of untreated trisomic animals, suggesting a need for ongoing therapy, she said at the Society for Maternal-Fetal Medicine meeting.

The results have sparked anticipation about the peptides' use in patients with Down's.

"[One of the peptides] has already gone through all the toxicology studies and is in phase II clinical trials for Alzheimer's disease," said Dr. Spong. "The hope would be that potentially this would have application in other things as well."

Newborns with Down's syndrome have altered levels of vasoactive intestinal peptide, which releases and regulates multiple neuropeptides, including the neuroprotective peptides known as NAP and SAL, said Dr. Spong. Previous studies showed that administration of NAP and SAL to trisomic mice during pregnancy prevented developmental delay.

In the current study, investigators examined the potential for NAP plus SAL to prevent learning deficits in adult trisomic male mice given either NAP plus SAL or placebo. Their learning ability was assessed by means of a Morris water maze, which requires animals to use visual cues to locate a platform hidden in a pool of water.

Beginning on day four, the animals had four water maze trials daily for five days. The time required to locate the platform reflected spatial learning. On days nine and 10 the animals underwent a test of memory retention, determined by the amount of time a mouse stayed in the water pool quadrant where the hidden platform had been placed.

During the five days of testing, the performance of trisomic mice treated with NAP plus SAL did not differ from that of the control group (P>0.05) and was significantly better as compared with untreated trisomic animals (P<0.001).

On treatment day nine, the treated trisomic animals averaged about 10 seconds in the correct quadrant of the water pool, which was not different from the control animals, whose time in the correct quadrant averaged about 10 seconds. In contrast, untreated animals were in the correct area for only about four seconds of the timed test.

Ten days after stopping treatment, the mice repeated the memory retention test. Control animals remained in the correct quadrant of the water maze for about 14 seconds, whereas the treated and untreated trisomic animals had almost identical times of about eight seconds.

Two other preclinical studies reported at the SMFM meeting provided insights into the underlying mechanisms involved in preventing memory deficit in the Down' syndrome model.

One study showed that treatment with NAP plus SAL significantly (P=0.02) increased expression to control levels of the N-methyl-d-aspartate subunit NR2A, which was decreased in trisomic mice compared with controls (P<0.05). NR2A increases long-term potentiation or synaptic strengthening, a key step in memory development.

In the second study, investigators showed that treatment with NAP plus SAL prevented dysregulation of vasoactive intestinal peptide (increased levels compared with control, P<0.05) and activity-dependent neuroprotective peptide (decreased levels compared with control, P<0.05) in trisomic mice (P<0.05), resulting in peptide levels similar to those of control animals.

Dr. Spong and co-authors reported no disclosures.

Action Points Source: Society of Maternal-Fetal Medicine

Toso L, et al "Prevention of learning deficit in a Down syndrome mouse model" Am J Obstet Gynecol 2007; 197(suppl): S3. Abstract 6.

Vink J, et al "Learning deficit prevention by NAP+SAL includes NMDA receptors in Down syndrome model" Am J Obstet Gynecol 2007; 197(suppl): S129. Abstract 433.

Vink J, et al "Prevention of Down syndrome learning deficits mediated through neuroprotective peptides, vasoactive intestinal peptide (VIP) and activity dependent neuroprotective peptide (ADNP)" Am J Obstet Gynecol 2007; 197(suppl): S174. Abstract 606.

Society of Maternal-Fetal Medicine Abstracts

PREVENTION OF LEARNING DEFICIT IN A DOWN SYNDROME MOUSE MODEL LAURA TOSO¹, ANDREA JOHNSON¹, STEPHANIE BISSELL¹, ROBIN ROBERSON¹, JOY VINK², DANIEL ABEBE¹, CATHERINE SPONG¹, ¹National Institutes of Health (NIH), NICHD & NIAAA, Bethesda, Maryland, ²Georgetown University, Department of ObGyn, Washington, District of Columbia
OBJECTIVE: Down syndrome (DS) is the most common genetic cause of mental retardation. In DS there is a glial deficit which induces anomalies in neurotrophins, including Activity Dependent Neuroprotective Protein and Activity. Dependent Neurotrophic Factor. Previously we have shown that their active fragments NAP+SAL prevented delay in behavioral milestones achievement in the Ts65Dn (Ts) mouse, a DS model. The objective of this study was to test if NAP+SAL prevent the adult DS learning deficit.
STUDY DESIGN: 9-12 month old Ts male mice were treated for 10 consecutive days with either D-NAP+D-SAL or placebo. From treatment day 4 mice were tested, for learning on the Morris watermaze for 5 days where latency to find a hidden platform by using visual cues is a measure of learning. Probe tests for long term memory were performed on treatment day 9 and 10 days later (after treatment stopped). Statistics included Bonferroni-Dunn with P<0.05 significant.
RESULTS: 15 Control, 4 Ts and 9 Ts+NAP+SAL were tested. Ts animals did not learn (P<0.001) over the 5-day period vs. the control. Ts animals treated with NAP+SAL learned significantly better than the Ts mice (P<0.001). On treatment day 9 Ts+NAP+SAL retained learning, with results similar to the controls (P>0.05). However, 10 days after therapy, Ts+NAP+SAL did not maintain learning in the probe test.
CONCLUSION: Postnatal treatment with peptides NAP+SAL prevented learning deficit in a model for DS. Possible mechanisms of action include overcoming the glial deficit.

OBJECTIVE: Down Syndrome (DS, trisomy 21) is a major cause of mental retardation affecting 1/800 newborns. Using a Ts65Dn mouse model for DS and the Morris watermaze to assess learning, we have show a learning deficit (Toso, 2007) in the adult Ts65Dn mouse as compared to wild type. NMDA receptors, specifically, the NR2B subunit is responsible for enhanced synaptic plasticity in paradigms of learning and memory. The expression of KIF17, a motor protein which transports NR2B subunits into the synaptic region, is shown to be parallel to increasing and decreasing expression of synaptic NR2B. While a down regulation of KIF17 is concomitant with an increase in less plastic synaptic NR2A, subunit expression (Hirokawa, 2004). Our objective was to evaluate the expression of NR2B, NR2A and KIF17 in a mouse model of DS to correlate to mechanisms underlying learning deficits in Ts65Dn adult mice.
STUDY DESIGN: Using the well established Ts65Dn model for Down Syndrome (DS), adult brains (40-60 weeks old) were collected and Western blot analysis performed with antibodies for NR2A, NR2B and KIF17 and quantified using N1H Image software and actin standardization. Comparisons were made between DS (trisomic) and control (wild type) animals with ANOVA, P<0.05 was considered significant.
RESULTS: Brains from 4 DS and 4 control (wild type) from four litters were studied. Western blot revealed no significant difference in the levels of NR2A (P=0.79) and NR2B (P=0.96) in DS as compared to the wild type (control) animals. However there was a significant increase in KIF17 (P=0.02) expression in our control (wild type) as compared to the DS animals/
CONCLUSION: Although we found no significant changes in protein expression of total NR2A or NR2B subunits in the WT vs. Ts65Dn mice, there is a significant decrease in expression in KIF17 motor protein in the Ts65Dn animals. This may indicate a possible decrease in synaptic NR2B subunit as well as an increase in synaptic NR2A subunit which may underlie the learning deficit seen in the adult Ts65Dn mice.

OBJECTIVE: A glial deficit underlies the learning deficit in Down syndrome (DS). Vasoactive Intestinal Peptide (VTP) stimulates glial cells to release ADNF and ADNP, neurotrophins involved in nervous system development. In DS, VIP and ANDP are altered, due to the glial deficit. In the Ts65Dn mouse model for DS we showed that VIP, ADNP and GFAP (a glial marker) are altered. We also showed that prenatal treatment with the active fragments of ADNP & ADNF (NAP & SAL) prevented developmental delay in Ts65Dn mice. Our objective was to see if NAP+SAL prevented the glial deficit in DS.
STUDY DESIGN: Pregnant Ts65Dn females were treated on gestational days 8-12 with either NAP+SAL or placebo. Brains from 10-month-old mice (4Ts, 4Control and 3Ts+NAP+SAL from 3 litters) were collected and calibrator-normalized rt-PCR was performed with primers for VIP, ADNP and GFAP with GAPDH standardization. Pups were genotyped as trisomic (Ts) or euploid (control). Statistics included Fisher PLSD with P<0.05 significant.
RESULTS: Expression of ADNP and GFAP were downregulated in Ts and treatment with NAP+SAL prevented downregulation (both P<0.05). VIP was increased in the Ts mice, treatment with NAP+SAL did not prevent the upregulation (P>0.05).
CONCLUSION: Prenatal treatment with NAP+SAL prevented the glial deficit in a model for DS and restored the appropriate level of ADNP and GFAP. The persistence of VIP upregulation suggests that other pathways regulate its release. Prevention of the glial deficit may underlie NAP+SAL protection against developmental delay and learning deficit in DS.

LEARNING DEFICIT PREVENTION BY NAP+SAL INCLUDES NMDA RECEPTORS IN A DOWN SYNDROME MODEL JOY VINK¹, LAURA TOSO², ROBIN ROBERSON², DANIEL ABEBE³, CATHERINE SPONG², ¹Georgetown University, Washington, District of Columbia, ²National Institutes of Health (NIH), Bethesda, Maryland, ³NICHD, SDMP, Bethesda, Maryland
OBJECTIVE: Down Syndrome (DS) is the most common genetic cause of mental retardation. NMDA and GAEA receptors are vital components of long term potentiation (LTP) and learning. Of the NMDA subunits, NR2B is more plastic and increases LTP, while NR2A is less plastic and decreases LTP. The GABAα5 subunit inhibits overstimulation and thus apoptosis of NMDA receptors. NR2B, NR2A and GABAα5 are decreased in adult Ts65Dn mice, a DS model, and treatment of adult Ts65Dn mice with neuroprotective peptides, NAP+SAL, prevented learning deficits. We investigated if this prevention is mediated through alterations in NR2B, NR2A and GABAα5.
STUDY DESIGN: Adult Ts65Dn mice were treated with NAP+SAL or placebo. After demonstrating learning deficit prevention, 4 brains per group (from 3 litters) were dissected. Gene expression for NR2B, NR2A and GABAα5 primers with GAPDH standardization was determined with calibrator-normalized relative Real Time (RT)-PCR. Statistics included Fisher PLSD with P<0.05 significant.
RESULTS: NR2B, NR2A and GABAα5 are decreased in adult trisomic (Ts) mice with respect to the control (all P<0.05). Treatment with NAP+SAL increased NR2B expression to control levels (P=0.02) but did not affect NR2A or GABAα5 expression.
CONCLUSION: NAP+SAL's mechanism of adult learning enhancement involves increasing the expression of the more-plastic NMDA subunit, NR2B, which facilitates learning, and not the less plastic subunit, NR2A, or GABAα5 expression. This may explain, at least in part, the mechanism involved in preventing learning deficits in Down Syndrome mice.

PREVENTION OF DOWN SYNDROME LEARNING DEFICITS MEDIATED THROUGH NEUROPROTECTIVE PEPTIDES, VASOACTIVE INTESTINAL PEPTIDE (VIP) AND ACTIVITY DEPENDENT NEUROPROTECTIVE PEPTIDE (ADNP) JOY VINK¹, LAURA TOSO², ROBIN ROBERSON², DANIEL ABEBE³, CATHERINE SPONG², ¹Georgetown University, Washington, District of Columbia, ²National Institutes of Health (NIH), Bethesda, Maryland, ³National Institutes of Health (NIH), Unit on Perinatal and Developmental Neurobiology, NICHD & NIAAA, Bethesda, Maryland
OBJECTIVE: Down Syndrome (DS) is the most common genetic cause of mental retardation. VIP regulates glial cell release of ADNP. In DS, a glial cell deficit exists, resulting in decreased ADNP and VIP upregulation. We showed that learning deficit in Ts65Dn mice, a DS model, is associated with decreased ADNP and that postnatal treatment of Ts65Dn mice with neuroprotective peptides, NAP+SAL, prevented the learning deficit. To understand the mechanism of learning deficit prevention, we treated adult Ts65Dn mice with NAP+SAL and evaluated GFAP (a glial cell marker), VIP and ADNP expression in their brains after learning assess.
STUDY DESIGN: Adult mice were treated with NAP+SAL or placebo. After demonstrating learning deficit prevention in trisomic (Ts) mice, 4 brains from each group (from 3 litters) were dissected. Calibrator-normalized relative Real Time (RT)-PCR with GAPDH standardization was used for gene expression. Statistics included Fisher PLSD with P<0.05 significant.
RESULTS: In adult Ts brains, GFAP and ADNP expression were decreased and VIP increased vs. controls (all P<0.05). Treatment with NAP+SAL prevented ADNP and VIP dysregulation, with levels similar to control (all P<0.05). NAP+SAL did not prevent GFAP down-regulation.
CONCLUSION: Prevention of Down Syndrome learning deficits by NAP+SAL is mediated, at least in part, through VIP and ADNP, however the action on glial cells does not prevent GFAP down-regulation. Further studies on glial cell function are needed to understand this mechanism.

Web Wanderings

Father's Journal

Could have been a nurse

Emmanuel was told by the waitress how impressed she was with his two gold medals and that she was an assistant swim coach and wished him luck at State, and that she would be there, so to the dismay of my wife, Emmanuel concluded that he is going to Special Olympics in the company of a waitress. Nothing wrong with that, I suppose.
Modern Eugenics: The Elimination of a People by Alan Sverdlik. Apr 21, 2008. URL: http://www.beaconcast.com/articles/20080422

The lightning rod in the debate is David Tolleson, a Roswell City Councilman and executive director of the National Down Syndrome Congress, a not-for-profit based in Dunwoody. Convinced that more couples would choose to continue their pregnancies if they better appreciated what it meant to raise a child with Down syndrome, the organization tries to insert its own positive perspective into a bitter national divide dominated by depressing medical statistics and doctors who feel obligated to describe the difficulties of life with a disabled child. [...]