Prospects for Improving Brain Function in Individuals with Down Syndrome

@article{Costa2013ProspectsFI,
  title={Prospects for Improving Brain Function in Individuals with Down Syndrome},
  author={Alberto C.S. Costa and Jonah J. Scott-McKean},
  journal={CNS Drugs},
  year={2013},
  volume={27},
  pages={679-702}
}
Down syndrome (DS), which results from an extra copy of chromosome 21 (trisomy 21), is the most common genetically defined cause of intellectual disability. Although no pharmacotherapy aimed at counteracting the cognitive and adaptive deficits associated with this genetic disorder has been approved at present, there have been several new promising studies on pharmacological agents capable of rescuing learning/memory deficits seen in mouse models of DS. Here, we will review the available mouse… 
View on Springer
ncbi.nlm.nih.gov
59 Citations
Highly Influential Citations
1
Background Citations
18
Methods Citations
3

59 Citations

Citation Type

Citation Type

Timing of therapies for Down syndrome: the sooner, the better
TLDR
This review summarizes what the authors know about the effects of pharmacotherapies during different life stages in mouse models of Down syndrome and gives reason to believe that treatments during pregnancy may rescue brain development in fetuses with DS.
Cognitive Impairment, Neuroimaging, and Alzheimer Neuropathology in Mouse Models of Down Syndrome.
TLDR
The validation of appropriate DS mouse models that mimic neurodegeneration and memory loss in humans with DS can be valuable in the study of novel preventative and treatment interventions, and may be helpful in pinpointing gene-gene interactions as well as specific gene segments involved in neurodegenersation.
PERSPECTIVES ON THE USE OF MOUSE MODELS OF DOWN SYNDROME IN TRANSLATIONAL RESEARCH INVOLVING VISUAL AND MOTOR FUNCTIONS
Down syndrome (DS) is a genetic disorder that results from the presence of one extra chromosome 21 in the cell nucleus (trissomy 21), and is the most frequent cause of intellectual disability of…
Long-term effects of neonatal treatment with fluoxetine on cognitive performance in Ts65Dn mice
TLDR
Findings suggest that the enduring outcome of neonatal treatment with fluoxetine may be due to MeCP2-dependent restoration of the 5-HT1A-R, and provide new hope for the therapy of DS.
Short- and long-term effects of neonatal pharmacotherapy with epigallocatechin-3-gallate on hippocampal development in the Ts65Dn mouse model of Down syndrome
TLDR
Findings show that treatment with EGCG carried out in the neonatal period rescues numerous trisomy-linked brain alterations, however, even during this, the most critical time window for hippocampal development, E GCG does not elicit enduring effects on the hippocampal physiology.
Epigallocatechin gallate: A useful therapy for cognitive disability in Down syndrome?
TLDR
Evidence in the Ts65Dn mouse model of DS shows that EGCG restores hippocampal development, although this effect is ephemeral, and protocols of periodic E GCG administration to individuals with DS (alone or in conjunction with other treatments) may prevent the disappearance of its effects.
Pharmacological Rescue of Dendritic Pathology in the Ts65Dn Mouse Model of Down Syndrome
Down syndrome (DS) is a genetic pathology characterized by brain hypotrophy and severe cognitive disability. Although defective neurogenesis is an important determinant of cognitive impairment, a…
Treatment with corn oil improves neurogenesis and cognitive performance in the Ts65Dn mouse model of Down syndrome
TLDR
It is shown for the first time that fatty acids have a positive impact on the brain of the Ts65Dn mouse model of DS, suggesting that a diet that is rich in fatty acids may exert beneficial effects on cognitive performance in individuals with DS without causing adverse effects.
Mitochondrial Abnormalities in Down Syndrome: Pathogenesis, Effects and Therapeutic Approaches
TLDR
The working hypothesis is that correcting the mitochondrial defect might improve the neurological phenotype and prevent DS-associated pathologies, thus providing a better quality of life for DS individuals and their families.
Glucagon-Like Peptide-1 Cleavage Product Improves Cognitive Function in a Mouse Model of Down Syndrome
TLDR
It is reported that systemic administration of GLP-1 (9-36) in Ts65Dn DS model mice of either sex resulted in decreased mitochondrial oxidative stress in hippocampus and improved dendritic spine morphology, increase of mature spines and reduction of immature spines.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 219 REFERENCES
On the Promise of Pharmacotherapies Targeted at Cognitive and Neurodegenerative Components of Down Syndrome
  • A. Costa
  • Psychology, Medicine
    Developmental Neuroscience
  • 2011
TLDR
A snapshot of potential pharmacotherapies for DS is provided, with emphasis on the recent results showing that the N-methyl-D-aspartate receptor antagonist memantine can reverse learning and memory deficits in Ts65Dn mice.
Synaptic and cognitive abnormalities in mouse models of down syndrome: Exploring genotype‐phenotype relationships
TLDR
Analysis of data from this and earlier studies points to genotype‐phenotype linkages in DS whose complexity ranges from relatively simple to quite complex.
Rescue of Synaptic Failure and Alleviation of Learning and Memory Impairments in a Trisomic Mouse Model of Down Syndrome
TLDR
It is shown that peripheral administration of Peptide 6, an 11-mer corresponding to an active region of ciliary neurotrophic factor, can inhibit learning and memory impairments in Ts65Dn mice, a trisomic mouse model of DS.
Function and regulation of Dyrk1A: towards understanding Down syndrome
TLDR
The evidence supporting a role for Dyrk1A in DS, especially DS pathogenesis, is summarized and several natural and synthetic compounds have been identified as DyrK1A inhibitors.
Early Pharmacotherapy Restores Neurogenesis and Cognitive Performance in the Ts65Dn Mouse Model for Down Syndrome
TLDR
Results show that early pharmacotherapy with a drug usable by humans can correct neurogenesis and behavioral impairment in a model for DS, and that proliferation was completely rescued by fluoxetine.
The neurobiologie consequences of down syndrome
TLDR
To elucidate the mechanisms responsible for Down Syndrome abnormalities, identification of the genes located in the distal part of HSA 21 and the systematic study of animal model systems with close genetic homology are essential.
Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial
TLDR
It is hypothesized that memantine therapy would improve test scores of young adults with DS on measures of episodic and spatial memory, which are generally considered to be hippocampus dependent, and a significant improvement in the memantine group in one of the secondary measures associated with the primary hypothesis is found.
Comprehensive behavioral phenotyping of Ts65Dn mouse model of Down Syndrome: Activation of β1-adrenergic receptor by xamoterol as a potential cognitive enhancer
TLDR
It is demonstrated that this mouse model of Down syndrome displays cognitive deficits which are mediated by an imbalance in the noradrenergic system, and a selective activation of β1-ADR does restore some of these behavioral deficits.
Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model
TLDR
Evidence is provided that vitamin E delays onset of cognitive and morphological abnormalities in a mouse model of DS, and may represent a safe and effective treatment early in the progression of DS neuropathology.
Hippocampal Long-Term Potentiation Suppressed by Increased Inhibition in the Ts65Dn Mouse, a Genetic Model of Down Syndrome
TLDR
Several lines of evidence suggest that inhibition in the Ts65Dn dentate gyrus was enhanced, at least in part, because of presynaptic abnormalities, which raises the possibility that similar changes contribute to abnormalities in learning and memory in people with DS and, perhaps, in other developmental disorders with cognitive failure.
...
1
2
3
4
5
...