Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome

Overview

Journal eNeuro

Specialty Neurology

Date 2016 Nov 16

PMID 27844057

Citations 23

Authors

Silvina Catuara-Solarz

Jose Espinosa-Carrasco

Ionas Erb

Klaus Langohr

Juan Ramon Gonzalez

Cedric Notredame

Mara Dierssen

Affiliations

Soon will be listed here.

Abstract

Intellectual disability in Down syndrome (DS) is accompanied by altered neuro-architecture, deficient synaptic plasticity, and excitation-inhibition imbalance in critical brain regions for learning and memory. Recently, we have demonstrated beneficial effects of a combined treatment with green tea extract containing (-)-epigallocatechin-3-gallate (EGCG) and cognitive stimulation in young adult DS individuals. Although we could reproduce the cognitive-enhancing effects in mouse models, the underlying mechanisms of these beneficial effects are unknown. Here, we explored the effects of a combined therapy with environmental enrichment (EE) and EGCG in the Ts65Dn mouse model of DS at young age. Our results show that combined EE-EGCG treatment improved corticohippocampal-dependent learning and memory. Cognitive improvements were accompanied by a rescue of cornu ammonis 1 (CA1) dendritic spine density and a normalization of the proportion of excitatory and inhibitory synaptic markers in CA1 and dentate gyrus.

Citing Articles

A bibliometric analysis of studies on environmental enrichment spanning 1967-2024: patterns and trends over the years.

Singhal G, Baune B Front Behav Neurosci. 2024; 18:1501377.

PMID: 39697184 PMC: 11652173. DOI: 10.3389/fnbeh.2024.1501377.

Pleiotropic effects of trisomy and pharmacologic modulation on structural, functional, molecular, and genetic systems in a Down syndrome mouse model.

Llambrich S, Tielemans B, Salien E, Atzori M, Wouters K, Van Bulck V Elife. 2024; 12.

PMID: 38497812 PMC: 10948151. DOI: 10.7554/eLife.89763.

Ts66Yah, a mouse model of Down syndrome with improved construct and face validity.

Duchon A, Muniz Moreno M, Chevalier C, Nalesso V, Andre P, Fructuoso-Castellar M Dis Model Mech. 2022; 15(12).

PMID: 36374158 PMC: 9789398. DOI: 10.1242/dmm.049721.

Green Tea Catechins Attenuate Neurodegenerative Diseases and Cognitive Deficits.

Afzal O, Dalhat M, Altamimi A, Rasool R, Alzarea S, Almalki W Molecules. 2022; 27(21).

PMID: 36364431 PMC: 9655201. DOI: 10.3390/molecules27217604.

Green Tea Catechins Modulate Skeletal Development with Effects Dependent on Dose, Time, and Structure in a down Syndrome Mouse Model.

Llambrich S, Gonzalez-Colom R, Wouters J, Roldan J, Salassa S, Wouters K Nutrients. 2022; 14(19).

PMID: 36235819 PMC: 9572077. DOI: 10.3390/nu14194167.

References

Martinez-Cue C, Baamonde C, Lumbreras M, Paz J, Davisson M, Schmidt C . Differential effects of environmental enrichment on behavior and learning of male and female Ts65Dn mice, a model for Down syndrome. Behav Brain Res. 2002; 134(1-2):185-200. DOI: 10.1016/s0166-4328(02)00026-8. View

Arque G, Fotaki V, Fernandez D, Martinez de Lagran M, Arbones M, Dierssen M . Impaired spatial learning strategies and novel object recognition in mice haploinsufficient for the dual specificity tyrosine-regulated kinase-1A (Dyrk1A). PLoS One. 2008; 3(7):e2575. PMC: 2481280. DOI: 10.1371/journal.pone.0002575. View

Seidl R, Cairns N, Lubec G . The brain in Down syndrome. J Neural Transm Suppl. 2002; (61):247-61. DOI: 10.1007/978-3-7091-6262-0_20. View

Altafaj X, Dierssen M, Baamonde C, Marti E, Visa J, Guimera J . Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. Hum Mol Genet. 2001; 10(18):1915-23. DOI: 10.1093/hmg/10.18.1915. View

Reynolds G, Warner C . Amino acid neurotransmitter deficits in adult Down's syndrome brain tissue. Neurosci Lett. 1988; 94(1-2):224-7. DOI: 10.1016/0304-3940(88)90299-6. View

Maei H, Zaslavsky K, Teixeira C, Frankland P . What is the Most Sensitive Measure of Water Maze Probe Test Performance?. Front Integr Neurosci. 2009; 3:4. PMC: 2659169. DOI: 10.3389/neuro.07.004.2009. View

Lott I, Dierssen M . Cognitive deficits and associated neurological complications in individuals with Down's syndrome. Lancet Neurol. 2010; 9(6):623-33. DOI: 10.1016/S1474-4422(10)70112-5. View

Ji J, Lee H, Argiropoulos B, Dorrani N, Mann J, Martinez-Agosto J . DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies. Eur J Hum Genet. 2015; 23(11):1473-81. PMC: 4613469. DOI: 10.1038/ejhg.2015.71. View

Kleschevnikov A, Belichenko P, Faizi M, Jacobs L, Htun K, Shamloo M . Deficits in cognition and synaptic plasticity in a mouse model of Down syndrome ameliorated by GABAB receptor antagonists. J Neurosci. 2012; 32(27):9217-27. PMC: 3411326. DOI: 10.1523/JNEUROSCI.1673-12.2012. View

10.

Ramirez-Rodriguez G, Ocana-Fernandez M, Vega-Rivera N, Torres-Perez O, Gomez-Sanchez A, Estrada-Camarena E . Environmental enrichment induces neuroplastic changes in middle age female Balb/c mice and increases the hippocampal levels of BDNF, p-Akt and p-MAPK1/2. Neuroscience. 2013; 260:158-70. DOI: 10.1016/j.neuroscience.2013.12.026. View

11.

Dias G, Cavegn N, Nix A, do Nascimento Bevilaqua M, Stangl D, Zainuddin M . The role of dietary polyphenols on adult hippocampal neurogenesis: molecular mechanisms and behavioural effects on depression and anxiety. Oxid Med Cell Longev. 2012; 2012:541971. PMC: 3395274. DOI: 10.1155/2012/541971. View

12.

Escorihuela R, Vallina I, Martinez-Cue C, Baamonde C, Dierssen M, Tobena A . Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome. Neurosci Lett. 1998; 247(2-3):171-4. DOI: 10.1016/s0304-3940(98)00317-6. View

13.

Leger M, Quiedeville A, Bouet V, Haelewyn B, Boulouard M, Schumann-Bard P . Object recognition test in mice. Nat Protoc. 2013; 8(12):2531-7. DOI: 10.1038/nprot.2013.155. View

14.

Pennington B, Moon J, Edgin J, Stedron J, Nadel L . The neuropsychology of Down syndrome: evidence for hippocampal dysfunction. Child Dev. 2003; 74(1):75-93. DOI: 10.1111/1467-8624.00522. View

15.

Souchet B, Guedj F, Penke-Verdier Z, Daubigney F, Duchon A, Herault Y . Pharmacological correction of excitation/inhibition imbalance in Down syndrome mouse models. Front Behav Neurosci. 2015; 9:267. PMC: 4611057. DOI: 10.3389/fnbeh.2015.00267. View

16.

Fernandez F, Morishita W, Zuniga E, Nguyen J, Blank M, Malenka R . Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat Neurosci. 2007; 10(4):411-3. DOI: 10.1038/nn1860. View

17.

Coussons-Read M, Crnic L . Behavioral assessment of the Ts65Dn mouse, a model for Down syndrome: altered behavior in the elevated plus maze and open field. Behav Genet. 1996; 26(1):7-13. DOI: 10.1007/BF02361154. View

18.

Catuara-Solarz S, Espinosa-Carrasco J, Erb I, Langohr K, Notredame C, Gonzalez J . Principal Component Analysis of the Effects of Environmental Enrichment and (-)-epigallocatechin-3-gallate on Age-Associated Learning Deficits in a Mouse Model of Down Syndrome. Front Behav Neurosci. 2015; 9:330. PMC: 4675859. DOI: 10.3389/fnbeh.2015.00330. View

19.

Demas G, Nelson R, Krueger B, Yarowsky P . Spatial memory deficits in segmental trisomic Ts65Dn mice. Behav Brain Res. 1996; 82(1):85-92. DOI: 10.1016/s0166-4328(97)81111-4. View

20.

Brown M, Warburton E, Aggleton J . Recognition memory: material, processes, and substrates. Hippocampus. 2010; 20(11):1228-44. DOI: 10.1002/hipo.20858. View