Neurodevelopment is defined as the brain’s development of neurological pathways that influence performance or functioning. Environmental Enrichment (EE) is a form of neurodevelopment accessible to children with Down Syndrome at birth.
However, despite its beneficial effects it is not sufficient on its own to promote long term changes of the nervous system or significant developmental changes in children with Down Syndrome (DS) . Discussed here, are adjuvant and alternative therapies which efficiently enhance neurological development in children with DS.
Neurodevelopment and Down Syndrome
by Gabi Giacomin
It is well documented in research that the structure of the Down Syndrome brain is altered due to genes located on chromosome 21 which affect the brain’s ability to function properly. People with Down Syndrome experience difficulties with executive function, spatial learning and memory. This occurs because of alterations in brain structure, synapses and neurochemistry [2, 3]. A reduction in the number of dendrites (branches) and complex changes in the hippocampus affects proper functioning of synapses (ends of neurons which pass chemical and electrical signals to other neurons) . In the DS brain there is also a disruption in the balance between excitatory and inhibitory neuronal systems . This causes problems with neural plasticity which is essential for cognition (acquiring knowledge and learning through experience).
EE is a form of neurodevelopment based on holistic stimulation of the brain. It recognises all parts of the cerebrum are connected, and stimulation of one area of the brain stimulates other areas . This is the reason reading is encouraged at a young age, as reading stimulates other cortical functions, including speech. Instead of using speech as the foundation for reading, reading is used to stimulate speech . EE is based on a combination of stimulation using inanimate objects, social stimulation and exercise. Stimulation can be auditory, visual, tactile and social. EE promotes synaptic plasticity, the growth of neurons and epigenetic changes .
Exercise stimulates neural plasticity. This enhances neuronal growth, learning and cognition seen in the hippocampus, cerebellum, cerebral cortex and throughout the brain . Exercise improves academic achievement and intelligence in typical children and those with cognitive damage .
Providing your child with EE, partially improves these altered neurological characteristics . However, if used in combination with phytonutrients, such as Green Tea, will promote long term changes of the nervous system and significant developmental changes in children with Down Syndrome (DS) .
Recently, it was discovered that EGCg, a neuro-protective catechin found in Green Tea, significantly improved cognitive ability in people with DS and in mouse models . It increased synaptic plasticity in vitro  and restored excitatory/ inhibitory imbalances in DS mouse models . It inhibits DYRK1a  whose over expression leads to structural neurological and cognitive changes in DS .
Current research has found that the combination of EE and EGCg was very effective to recover neurophysiology and enhance cognition in youths with DS . The combined treatment increased spinal density of dendrites (branches), normalised inhibitory and excitatory synapses and enhanced learning .
Last year, 2016, details of a landmark pilot study were published analysing effectiveness of the IAHP’s neurodevelopment program for children with a focus on Down Syndrome (DS). The study accessed a database of 248 DS children who had undertaken the program over a period of 25 years .
While the IAHP program is considered to be a form of EE, it is unique. The IAHP recommend treatment before the age of five, unlike some therapies which wait until the onset of symptoms. Important components of the program include crawling on the floor, the progression of crawling to running at an early age, passive exercise for those not able to crawl (patterning), brachiating by moving across a monkey bar, early reading and maths, gymnastics and athletics, nutritional optimisation and avoidance of drugs that interfere with brain development . Sensory stimulation may be auditory, visual, tactile or social  and promotes neurogenesis, learning, cognition and brain growth.
The positive effects of EE on brain development include changes in brain structure and enhanced activity of neurotransmitters and neurochemistry . Improvements in problem solving, memory, learning and social interactions including improvement of brain injury, developmental delay and genetic alterations, as in DS .
Exercise has an extremely positive effect on the brain including the stimulation of neural plasticity leading to the growth of neurons, and improvements in learning and cognition . Exercise improves academic achievement and intelligence in typical children as well as those with brain injury . In combination with mental stimulation, exercise enhances the growth of neurons and improves neuron survival .
The rate of improvement using these techniques more than doubles brain growth. This is consistent with prior studies looking at adopted orphans and animals, despite the fact it seems extraordinary . The potential for development for children with DS is greater than most people realise .
Overall, combined treatment of EE with EGCg simultaneously targeted several abnormal processes underlying intellectual disability in DS, and is considered optimal treatment as intervention to prevent disease in the DS population.
- Mahoney G, Wheeden CA, Perales F (2004) Relationship of preschool special education outcomes to instructional practices and parent-child interaction. Res Dev Disabil 25:539 –558.
- Lott IT, Dierssen M (2010) Cognitive deficits and associated neuro- logical complications in individuals with Down’s syndrome. Lancet Neurol 9:623–633.
- Dierssen M (2012) Down syndrome: the brain in trisomic mode. Nat Rev Neurosci 13:844–858.
- Becker LE, Armstrong DL, Chan F (1986) Dendritic atrophy in chil- dren with Down’s syndrome. Ann Neurol 20:520–526.
- Reynolds GP, Warner CE (1988) Amino acid neurotransmitter deficits in adult Down’s syndrome brain tissue. Neurosci Lett 94:224 –227.
- Baggot P J, Baggot R M. Doubling the Rate of Neurologic Development in Down Syndrome: a Pilot Study. Journal of American Physicians and Surgeons Volume 21 Number 2 Summer 2016
- Diamond MC, Krech D, Rosenzweig MR. The effects of an enriched environment on the histology of the rat cerebral cortex. J Comp Neurol 1964;123:111-120.
- Sale A, Berardi N, Maffei L (2014) Environment and brain plasticity: towards an endogenous pharmacotherapy. Physiol Rev 94:189– 234
- Thomas AG, Dennis A, Bandettini PA, Johansen-Berg H. The effects of aerobic activity on brain structure. Front Psychol 2012;3(86):1-9
- Tomporowski PD, Davis CL, Miller PH, Naglieri JA. Exercise and children’s intelligence, cognition and academic achievement. Educ Psychol Rev 2008;20:111-131.
- Martínez-Cué C, Baamonde C, Lumbreras M, Paz J, Davisson MT, Schmidt C, Dierssen M, Flórez J (2002) Differential effects of environmental enrichment on behavior and learning of male and female Ts65Dn mice, a model for Down syndrome. Behav Brain Res 134:185–200
- De la Torre R, et al. (2014) Epigallocatechin-3-gallate, a DYRK1A inhib- itor, rescues cognitive deficits in Down syndrome mouse models and in humans. Mol Nutr Food Res 58:278–288.
- Xie W, Ramakrishna N, Wieraszko A, Hwang Y-W (2008) Promotion of neuronal plasticity by (-)-epigallocatechin-3-gallate. Neurochem Res 33:776–783.
- Souchet B, Guedj F, Penke-Verdier Z, Daubigney F, Duchon A, Herault Y, Bizot J-C, Janel N, Créau N, Delatour B, Delabar JM (2015) Pharmacological correction of excitation/inhibition imbal- ance in Down syndrome mouse models. Front Behav Neurosci 9:267.
- Bain J, McLauchlan H, Elliott M, Cohen P (2003) The specificities of protein kinase inhibitors: an update. Biochem J 371:199–204.
- Altafaj X, Dierssen M, Baamonde C, Martí E, Visa J, Guimera` J, Oset M, González JR, Flórez J, Fillat C, Estivill X (2001) Neurodevelop- mental delay, motor abnormalities and cognitive deficits in trans- genic mice overexpressing Dyrk1A (minibrain), a murine model of Down’s syndrome. Hum Mol Genet 10:1915–1924.
- Silvina Catuara-Solarz, Jose Espinosa-Carrasco, Ionas Erb, Klaus Langohr, Juan Ramon Gonzalez, Cedric Notredame, and Mara Dierssen. Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome. eNeuro September/October 2016, 3(5) e0103-16.2016 1–18
- Rosenzweig MR, Bennett EL, Hebert M, Morimoto H. Social grouping cannot account for cerebral effects of enriched environments. Brain Res 1978;153:536-576.
- Curlik DM 2nd, Shors TJ. Training your brain: Do mental and physical (MAP) training enhance cognition through the process of neurogenesis in the hippocampus? Neuropharmacology 2013; 64(Jan):506-514.