Short- and long-term effects of neonatal pharmacotherapy with epigallocatechin-3-gallate on hippocampal development in the Ts65Dn mouse model of Down syndrome

Epigallocatechin gallate: A useful therapy for cognitive disability in Down syndrome?

“…Mice received a daily injection of pure EGCG (25 mg/kg) in the postnatal period P3-P15 and the effects were examined both at treatment cessation (at P15) and after one month (at P45). 20 We found positive effects of the acute treatment, with restoration of neurogenesis, cellularity and connectivity in the hippocampus and neocortex. Treatment, however, had no long-term effects, and hippocampal neurogenesis and connectivity were once more impaired when mice reached 45 d of age.…”

“…20 It is important to note that the only study that examined DYRK1A activity in the Ts65Dn mouse showed marginal differences in comparison with euploid mice and marginal effects of EGCG on its activity. 18 However, due to the relatively small sample size in conjunction with the intrinsic phenotypic variability of Ts65Dn mice, further observations are required to confirm this finding.…”

“…If in Ts65Dn mice, unlike in TgDyrk1A mice, DYRK1A activity is less severely affected, this may imply that DYRK1A is not a major cause of brain and behavior impairment and may thus explain the inconsistent effects on behavior found in Ts65Dn mice treated with EGCG. Finally, it must be observed that in wild-type mice EGCG may have an adverse effect on behavior 17 and synaptic connections, 20 suggesting some caveats in treatment with EGCG as supplementation to enhance brain function. Conflicting results have also been reported for other rodent models.…”

“…17 This fits in with the disappearance of the effects of EGCG in the Ts65Dn mouse model. 20 However, it is important to note that in individuals with DS treatment with EGCG plus cognitive training for 12 months leads to effects that are partially retained after treatment discontinuation. 23 Although the effects of treatment are of small magnitude and involve a limited number of behaviors, this study suggests that EGCG may be used to ameliorate some aspects of cognitive performance in individuals with DS.…”

Modeling Fragile X syndrome in neurogenesis: An unexpected phenotype and a novel tool for future therapies

“…Consequently, some preclinical therapeutic approaches are targeting not only neonatal but also prenatal life 14 focusing on those molecules that can act on neurogenesis defects. 15,16 Starting from these considerations and from the fact that an effective specific therapy for FXS is not available yet, a mouse embryonic stem cell line displaying a reduced expression of Fmr1 by stable transfection of a specific shRNA directed against Fmr1 (shFmr1 ES) has been generated. 17 These cells do not display morphological abnormalities and cell cycle variations, however altered expression of a subset of genes mainly involved in neuronal differentiation and maturation determines a subjacent molecular pathology.…”