Deficiency of Adult Neurogenesis in the Ts65Dn Mouse Model of Down Syndrome

Belichenko, Pavel V.; Kleschevnikov, Alexander M.

doi:10.5772/24585

Cited by 2 publications

(2 citation statements)

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“…Several compounds that normalize adult neurogenesis in Ts65Dn mice (Bianchi et al, 2010;Contestabile et al, 2013) also normalize LTP and associated memory functions. We evaluated adult neurogenesis and we showed a decrease in cell proliferation in young Ts65Dn mice, which is consistent with previous results (Belichenko and Kleschevnikov, 2011;Clark et al, 2006).…”

Section: Discussionsupporting

confidence: 91%

“…In addition, we studied adult neurogenesis, since Ts65Dn mice show a reduction in cell proliferation (Belichenko and Kleschevnikov, 2011;Clark et al, 2006), that can be quantified by the number of cells expressing Ki67, an endogenous marker of cell proliferation. Consistent with previous reports, Ts65Dn male mice treated with vehicle for 7 days (i.p., last administration 24 h before brain perfusion) showed a decreased number of Ki67+ cells in the subgranular zone of the dentate gyrus (Fig.…”

Section: Cb1r Pharmacological Targeting Improves Hippocampal Synapticmentioning

confidence: 99%

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Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome

Navarro-Romero

Vázquez-Oliver

Gomis-González

et al. 2019

Neurobiology of Disease

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Intellectual disability is the most limiting hallmark of Down syndrome, for which there is no gold-standard clinical treatment yet. The endocannabinoid system is a widespread neuromodulatory system involved in multiple functions including learning and memory processes. Alterations of this system contribute to the pathogenesis of several neurological and neurodevelopmental disorders. However, the involvement of the endocannabinoid system in the pathogenesis of Down syndrome has not been explored before. We used the best-characterized preclinical model of Down syndrome, the segmentally trisomic Ts65Dn model. In male Ts65Dn mice, cannabinoid type-1 receptor (CB1R) expression was enhanced and its function increased in hippocampal excitatory terminals. Knockdown of CB1R in the hippocampus of male Ts65Dn mice restored hippocampal-dependent memory. Concomitant with this result, pharmacological inhibition of CB1R restored memory deficits, hippocampal synaptic plasticity and adult neurogenesis in the subgranular zone of the dentate gyrus. Notably, the blockade of CB1R also normalized hippocampal-dependent memory in female Ts65Dn mice. To further investigate the mechanisms involved, we used a second transgenic mouse model overexpressing a single gene candidate for Down syndrome cognitive phenotypes, the dual specificity tyrosinephosphorylation-regulated kinase 1A (DYRK1A). CB1R pharmacological blockade similarly improved cognitive performance, synaptic plasticity and neurogenesis in transgenic male Dyrk1A mice. Our results identify CB1R as a novel druggable target potentially relevant for the improvement of cognitive deficits associated with Down syndrome.

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Section: Discussionsupporting

confidence: 91%

Section: Cb1r Pharmacological Targeting Improves Hippocampal Synapticmentioning

confidence: 99%

Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome

Navarro-Romero

Vázquez-Oliver

Gomis-González

et al. 2019

Neurobiology of Disease

View full text Add to dashboard Cite

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Functional implications of hippocampal adult neurogenesis in intellectual disabilities

2013

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The development of strategies capable to promote nervous system plasticity in adulthood is nowadays an important aim in neuroscience to improve not only cognitive abilities but also to ameliorate pathological dysfunctions. Several studies have demonstrated that adult neurogenesis is regulated by many physiological and pathological stimuli at almost every stage, from proliferation of neuronal precursors until integration and activation of newly formed neurons in the preexisting network. We review the process of generating functional neurons from precursors in the adult brain and its implications in intellectual disability disorders.

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Deficiency of Adult Neurogenesis in the Ts65Dn Mouse Model of Down Syndrome

Cited by 2 publications

References 64 publications

Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome

Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome

Functional implications of hippocampal adult neurogenesis in intellectual disabilities

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