title: Rescue of synaptic failure and alleviation of learning and memory impairments in a trisomic mouse model of down syndrome.
abstract: Down syndrome (DS) is caused by the triplication of ∼240 protein-coding genes on chromosome 21 and is the most prevalent form of developmental disability. This condition results in abnormalities in many organ systems, as well as in intellectual retardation. Many previous efforts to understand brain dysfunction in DS have indicated that cognitive deficits are coincident with reduced synaptic plasticity and decreased neuronal proliferation. One therapeutic strategy for optimizing the microenvironment for neuronal proliferation and synaptic plasticity in the brain is the use of neurotrophins to restore the homeostasis of the brain biochemical milieu. Here, we show that peripheral administration of Peptide 6, an 11-mer corresponding to an active region of ciliary neurotrophic factor, amino acid residues 146 to 156, can inhibit learning and memory impairments in Ts65Dn mice, a trisomic mouse model of DS. Long-term treatment with Peptide 6 enhanced the pool of neural progenitor cells in the hippocampus and increased levels of synaptic proteins crucial for synaptic plasticity. These findings suggest a therapeutic potential of Peptide 6 in promoting functional neural integration into networks, thereby strengthening biologic substrates of memory processing.
authors.affiliation: Department of Neurochemistry, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Blanchard
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolognin
authors.forename: Muhammad Omar
authors.initials: MO
authors.lastname: Chohan
authors.forename: Ausma
authors.initials: A
authors.lastname: Rabe
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
authors.forename: Inge
authors.initials: I
authors.lastname: Grundke-Iqbal
mesh_terms: D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007858:Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
chemical_list: D020934:Ciliary Neurotrophic Factor; D010446:Peptide Fragments