Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome

Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities

Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome

Background: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. Methodology/Principal Findings: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased. Conclusions/Significance: We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals.Chelsee A. Hewitt, King-Hwa Ling, Tobias D. Merson, Ken M. Simpson, Matthew E. Ritchie, Sarah L. King, Melanie A. Pritchard, Gordon K. Smyth, Tim Thomas, Hamish S. Scott and Anne K. Vos

Effect of Refractive Correction on the Accuracy of Frequency-doubling Technology Matrix.

PURPOSE:: To investigate the effect of refractive correction on the reliability and accuracy of frequency-doubling technology (FDT) Matrix examinations. METHODS:: Forty-eight eyes of healthy people were submitted to the FDT Matrix 30/2 threshold program. They had experience in perimetry, normal eye examination, and negative history for glaucoma and/or neurological diseases. The subjects were randomized into groups A (24 subjects) and B (24 subjects). The FDT Matrix 30/2 examinations were carried out in 3 different sessions. At the first session, groups A and B underwent the examinations with their best refractive correction. In the second session, group A underwent the FDT 30/2 examination with best refractive correction and the group B without it. In the third session, the groups were matched and followed the same protocol. The perimetric and reliability indexes and the time of examination with or without correction were considered. The Student t test was used when the distribution of the data was normal, whereas Mann-Whitney when the distribution of the data was not normal. After a Bonferroni correction, a P value <0.001 was considered as statistically significant. RESULTS:: Mean deviation reduced statistically significantly when refractive correction was used (-2.65\ub13.71 vs. -1.41\ub13.51 dB; P<0.006). All the other perimetric indexes and data considered did not change significantly when the subjects did the examination with or without the refractive correction. CONCLUSIONS:: The statistically significant reduction of mean deviation obtained with corrective lens showed that a better general accuracy and reliability of FDT responses was obtained with refractive correction. Pattern standard deviation constancy with or without correction confirmed that a localized defect is the first sign of visual field defect and that the absence of differences of pattern standard deviation between the 2 sessions is related to the absence of pathologic conditions in the eyes studied. Finally, as FDT Matrix is less influenced by other nonconventional perimetric techniques by refractive errors, the use of corrective lens is advisable to improve the accuracy and reliability of the results obtained and to optimize their performance