Learning Deficit Blocked in Mouse Model of Down's

This is pretty promising research!! Hopefully it can be redone in persons with DS.

SMFM: Learning Deficit Blocked in Mouse Model of Down's

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)>

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).>

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)>P<0.05)>P<0.05),>

Primary source: Society of Maternal-Fetal Medicine
Source reference:
Toso L, et al "Prevention of learning deficit in a Down syndrome mouse model" Am J Obstet Gynecol 2007; 197(suppl): S3. Abstract 6.

Additional source: Society of Maternal-Fetal Medicine
Source reference:
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.

Additional source: Society of Maternal-Fetal Medicine
Source reference:
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.

http://www.medpagetoday.com/MeetingCoverage/SMFM/tb/8199