Reducing GABAA α5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of down syndrome.

Down syndrome (DS) is associated with neurological complications, including cognitive deficits that lead to impairment in intellectual functioning. Increased GABA-mediated inhibition has been proposed as a mechanism underlying deficient cognition in the Ts65Dn (TS) mouse model of DS. We show that chronic treatment of these mice with RO4938581 (3-bromo-10-(difluoromethyl)-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine), a selective GABA(A) α5 negative allosteric modulator (NAM), rescued their deficits in spatial learning and memory, hippocampal synaptic plasticity, and adult neurogenesis. We also show that RO4938581 normalized the high density of GABAergic synapse markers in the molecular layer of the hippocampus of TS mice. In addition, RO4938581 treatment suppressed the hyperactivity observed in TS mice without inducing anxiety or altering their motor abilities. These data demonstrate that reducing GABAergic inhibition with RO4938581 can reverse functional and neuromorphological deficits of TS mice by facilitating brain plasticity and support the potential therapeutic use of selective GABA(A) α5 NAMs to treat cognitive dysfunction in DS.

Chronic melatonin treatment rescues electrophysiological and neuromorphological deficits in a mouse model of Down syndrome.

The Ts65Dn mouse (TS), the most commonly used model of Down syndrome (DS), exhibits several key phenotypic characteristics of this condition. In particular, these animals present hypocellularity in different areas of their CNS due to impaired neurogenesis and have alterations in synaptic plasticity that compromise their cognitive performance. In addition, increases in oxidative stress during adulthood contribute to the age-related progression of cognitive and neuronal deterioration. We have previously demonstrated that chronic melatonin treatment improves learning and memory and reduces cholinergic neurodegeneration in TS mice. However, the molecular and physiological mechanisms that mediate these beneficial cognitive effects are not yet fully understood. In this study, we analyzed the effects of chronic melatonin treatment on different mechanisms that have been proposed to underlie the cognitive impairments observed in TS mice: reduced neurogenesis, altered synaptic plasticity, enhanced synaptic inhibition and oxidative damage. Chronic melatonin treatment rescued both impaired adult neurogenesis and the decreased density of hippocampal granule cells in trisomic mice. In addition, melatonin administration reduced synaptic inhibition in TS mice by increasing the density and/or activity of glutamatergic synapses in the hippocampus. These effects were accompanied by a full recovery of hippocampal LTP in trisomic animals. Finally, melatonin treatment decreased the levels of lipid peroxidation in the hippocampus of TS mice. These results indicate that the cognitive-enhancing effects of melatonin in adult TS mice could be mediated by the normalization of their electrophysiological and neuromorphological abnormalities and suggest that melatonin represents an effective treatment in retarding the progression of DS neuropathology.

Apoptosis in Down's syndrome: lessons from studies of human and mouse models.

Down syndrome (DS) is the most common chromosomal abnormality in humans. DS is characterized by a number of phenotypes, including the development of Alzheimer's disease-like pathology and immunological, hematological and cardiovascular alterations. Apoptosis or programmed cell death is physiologically involved in development and aging, as well as in numerous pathological processes. Altered apoptosis has been proposed as a putative mechanism underlying many DS phenotypes. Evidence from human and animal studies indicates that apoptosis does not have a prominent role in the disturbances found in brain development in trisomy 21. However, alterations in apoptosis have been associated with neurodegeneration in the aging DS brain, with impairments in general growth and with immunological, cardiovascular and oncological alterations. Altered apoptosis in DS is likely to be the result of the interplay between several chromosome 21 (Hsa21) and non-Hsa21 genes. The interplay between these genes may affect physiological programmed cell death either directly, by modifying the activity of the apoptotic pathways, or indirectly, by inducing degeneration and rendering the cell more vulnerable to apoptosis-inducing factors.

Long-term oral administration of melatonin improves spatial learning and memory and protects against cholinergic degeneration in middle-aged Ts65Dn mice, a model of Down syndrome.

Ts65Dn mice (TS), the most commonly used model of Down syndrome (DS), exhibit phenotypic characteristics of this condition. Both TS mice and DS individuals present cognitive disturbances, age-related cholinergic degeneration, and increased brain expression of ß-amyloid precursor protein (AßPP). These neurodegenerative processes may contribute to the progressive cognitive decline observed in DS. Melatonin is a pineal indoleamine that has been reported to reduce neurodegenerative processes and improve cognitive deficits in various animal models. In this study, we evaluated the potentially beneficial effects of long-term melatonin treatment on the cognitive deficits, cholinergic degeneration, and enhanced AßPP and ß-amyloid levels of TS mice. Melatonin was administered for 5 months to 5- to 6-month-old TS and control (CO) mice. Melatonin treatment improved spatial learning and memory and increased the number of choline acetyltransferase (ChAT)-positive cells in the medial septum of both TS and CO mice. However, melatonin treatment did not significantly reduce AßPP or ß-amyloid levels in the cortex or the hippocampus of TS mice. Melatonin administration did reduce anxiety in TS mice without inducing sensorimotor alterations, indicating that prolonged treatment with this indoleamine is devoid of noncognitive behavioral side effects (e.g., motor coordination, sensorimotor abilities, or spontaneous activity). Our results suggest that melatonin administration might improve the cognitive abilities of both TS and CO mice, at least partially, by reducing the age-related degeneration of basal forebrain cholinergic neurons. Thus, chronic melatonin supplementation may be an effective treatment for delaying the age-related progression of cognitive deterioration found in DS.

Economic-environmental assessment of silvo-pastoral systems in Colombia: An ecosystem service perspective.

Cattle production in Colombia has an important social and economic role but causes considerable environmental impacts, such as deforestation and greenhouse gas emissions by ruminants, particularly methane. Thus, technological innovations aimed at reducing these impacts must focus on both economic and environmental sustainability. Silvo-pastoral systems (SPS) offer productivity increases while generating environmental benefits and ecosystem services and are therefore at the center of debate around sustainable production alternatives. The objective of this article is to evaluate the economic-environmental performance of two proposed SPS for a cattle fattening system for the Colombian context: (i) Urochloa brizantha cv. Toledo and (ii) Urochloa hybrid cv. Cayman, both in association with Leucaena leucocephala trees for browsing and shade provision. They are compared with the respective base scenarios of only using the grasses in monocultures. The study consists of a financial analysis, which estimates potential profitability increases in beef production in the SPS, and an environmental evaluation, which estimates the monetary values of microclimatic regulation and reduction of methane emissions. The value of methane emission reductions is then integrated into a combined economic-environmental evaluation. Results show that both SPS improve the profitability indicators of the production system and reduce the probability of economic loss. Likewise, the reduction of methane emissions in the SPS is estimated at US$6.12 per cattle, and the economic value of microclimatic regulation at US$2,026 per hectare.

Potential Forage Hybrid Markets for Enhancing Sustainability and Food Security in East Africa.

The cattle sector is strategic for both the economic development and food security of Africa, but the low availability and quality of forage puts the most vulnerable population at risk. Hybrid forages are an alternative for enhancing both food security and sustainability of the sector but adoption levels are still low in Africa, which is related to various factors such as the availability of seeds. This document analyzes potential markets for new interspecific hybrids of Urochloa and potential hybrids of Megathyrsus maximus, adapted to the environmental conditions of eastern and partially western Africa, applying a four-step methodology based on estimating (i) required forage amounts for each country according to its dairy herd, (ii) potential hectares for forage cultivation based on (i), (iii) hectares that can be covered by the two hybrids of interest according to a Target Population of Environment approach, and (iv) potential market values for each country and hybrid. The results show a potential market of 414,388 ha for new interspecific hybrids of Urochloa and 528,409 ha for potential hybrids of Megathyrsus maximus, with approximate annual values of 73.5 and 101.1 million dollars, respectively. Ethiopia, Tanzania, and Kenya hold a market share of 70% for Urochloa, and South Sudan, Ethiopia, and Tanzania a 67% market share for Megathyrsus maximus. The results will help different actors in decision-making, i.e., regarding private sector investments in forage seed commercialization or public sector incentives supporting adoption processes, and thus contribute to increasing food security and sustainability in the region.

Mouse models of Down syndrome as a tool to unravel the causes of mental disabilities.

Down syndrome (DS) is the most common genetic cause of mental disability. Based on the homology of Hsa21 and the murine chromosomes Mmu16, Mmu17 and Mmu10, several mouse models of DS have been developed. The most commonly used model, the Ts65Dn mouse, has been widely used to investigate the neural mechanisms underlying the mental disabilities seen in DS individuals. A wide array of neuromorphological alterations appears to compromise cognitive performance in trisomic mice. Enhanced inhibition due to alterations in GABA(A)-mediated transmission and disturbances in the glutamatergic, noradrenergic and cholinergic systems, among others, has also been demonstrated. DS cognitive dysfunction caused by neurodevelopmental alterations is worsened in later life stages by neurodegenerative processes. A number of pharmacological therapies have been shown to partially restore morphological anomalies concomitantly with cognition in these mice. In conclusion, the use of mouse models is enormously effective in the study of the neurobiological substrates of mental disabilities in DS and in the testing of therapies that rescue these alterations. These studies provide the basis for developing clinical trials in DS individuals and sustain the hope that some of these drugs will be useful in rescuing mental disabilities in DS individuals.

Translational validity and implications of pharmacotherapies in preclinical models of Down syndrome.

Neurodevelopmental disorders are challenging to study in the laboratory, and despite a large investment, few novel treatments have been developed in the last decade. While animal models have been valuable in elucidating disease mechanisms and in providing insights into the function of specific genes, the predictive validity of preclinical models to test potential therapies has been questioned. In the last two decades, diverse new murine models of Down syndrome (DS) have been developed and numerous studies have demonstrated neurobiological alterations that could be responsible for the cognitive and behavioral phenotypes found in this syndrome. In many cases, similar alterations were found in murine models and in individuals with DS, although several phenotypes shown in animals have yet not been confirmed in the human condition. Some of the neurobiological alterations observed in mice have been proposed to account for their changes in cognition and behavior, and have received special attention because of being putative therapeutic targets. Those include increased oxidative stress, altered neurogenesis, overexpression of the Dyrk1A gene, GABA-mediated overinhibition and Alzheimer's disease-related neurodegeneration. Subsequently, different laboratories have tested the efficacy of pharmacotherapies targeting these alterations. Unfortunately, animal models are limited in their ability to mimic the extremely complex process of human neurodevelopment and neuropathology. Therefore, the safety and efficacy identified in animal studies are not always translated to humans, and most of the drugs tested have not demonstrated any positive effect or very limited efficacy in clinical trials. Despite their limitations, though, animal trials give us extremely valuable information for developing and testing drugs for human use that cannot be obtained from molecular or cellular experiments alone. This chapter reviews some of these therapeutic approaches and discusses some reasons that could account for the discrepancy between the findings in mouse models of DS and in humans, including: (i) the incomplete resemble of the genetic alterations of available mouse models of DS and human trisomy 21, (ii) the lack of evidence that some of the phenotypic alterations found in mice (e.g., GABA-mediated overinhibition, and alterations in adult neurogenesis) are also present in DS individuals, and (iii) the inaccuracy and/or inadequacy of the methods used in clinical trials to detect changes in the cognitive and behavioral functions of people with DS. Despite the shortcomings of animal models, animal experimentation remains an invaluable tool in developing drugs. Thus, we will also discuss how to increase predictive validity of mouse models.

Effects of chronic administration of SGS-111 during adulthood and during the pre- and post-natal periods on the cognitive deficits of Ts65Dn mice, a model of Down syndrome.

The Ts65Dn mouse is the most commonly used model of Down syndrome. This mouse shows many phenotypic characteristics present in people with Down syndrome, including behavioral and cognitive deficits. SGS-111 is a novel analogue of the nootropic piracetam, which prevents oxidative damage and apoptosis in both normal and Down syndrome human cortical neurons. In this work we tested the ability of chronic administration of SGS-111 to adult Ts65Dn mice to reverse the cognitive deficit found in these mice. Moreover, since oxidative stress has been reported as early as the fetal stage, SGS-111 was also administered to pregnant Ts65Dn females from the day of conception throughout the pregnancy and to Ts65Dn pups during their entire life (5 months), from birth to the end of the behavioral testing period. A characterization of the effects of SGS-111 treatment on Ts65Dn and control mice sensorimotor abilities, motor coordination, spontaneous activity, activity in the open field, exploration, anxiety and spatial and non-spatial short- and long-term learning and memory was performed. The behavioral characterization showed that chronic administration of the antioxidant SGS-111 reduced the hyperactivity shown by Ts65Dn mice in their home cage, in the open field and in the hole board test. SGS-111 administration during adulthood improved performance in the first session in the Morris water maze in control mice, and when administered during the pre- and post-natal periods, improved spatial learning in the control mice but not in Ts65Dn mice. Chronic SGS-111 administration failed to affect behavior and cognition in Ts65Dn mice.

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant.

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

Behavioral, cognitive and biochemical responses to different environmental conditions in male Ts65Dn mice, a model of Down syndrome.

Ts65Dn mouse is the most widely accepted model for Down syndrome. We previously showed that environmental enrichment improved spatial learning in female but deteriorated it in male Ts65Dn mice. This study analyzed the factors contributing to the disturbed cognition of male Ts65Dn mice after enriched housing, by allocating male control and Ts65Dn mice in four conditions after weaning: small (n = 2-3) and large group (n = 8-10) housing, and enriched housing in small (2-3) and large groups (8-10). Learning, aggressive behavior, anxiety-like behavior and biochemical correlates of stress were evaluated when Ts65Dn and control mice were 4-5 months old. Environmental enrichment in large mixed colonies of Ts65Dn and diploid littermates disturbed behavioral and learning skills of Ts65Dn mice in the Morris water maze. ACTH and testosterone levels were not modified in any group of mice. Ts65Dn and control mice subjected to enriched housing in large groups and Ts65Dn mice housed in large groups showed higher corticosterone levels. Aggressive behavior was evaluated by measuring the number of attacks performed in the presence of an intruder. Ts65Dn mice performed less attacks than controls in all conditions, especially after enriched housing, indicating subordination. In the plus maze, cognitive aspects (i.e. risk assessment) and motor components (open arm avoidance) of anxiety behavior were evaluated; no difference in any condition was found. It is suggested that an excess of social and/or physical stimulation in Ts65Dn mice may affect cognition by disturbing the emotional and behavioral components of the learning process.

Cell proliferation is reduced in the dentate gyrus of aged but not young Ts65Dn mice, a model of Down syndrome.

Reduced number of neurons is a common feature in Down's syndrome (DS) brains. Since reduced neuronal number also occurs in the dentate gyrus of Ts65Dn mice (TS), a model for DS, hippocampal cell proliferation and survival were analyzed in young and old TS mice. For evaluating proliferation and survival, half of the mice were sacrificed 1 day, and the other half 30 days after the last bromodeoxyuridine injection, respectively. No difference was found in the number of proliferating or surviving cells of young TS and control mice. An age-associated decline in total cell number and density has been found in both genotypes, this decline being more pronounced in TS animals. Thus, aged TS mice showed reduced cell proliferation and density of surviving cells compared to CO mice. Due to the putative involvement of newborn cells in the dentate gyrus in learning processes, the reduced proliferative capacity found in TS mice could be involved in the cognitive problems found in this model of Down syndrome.

Opioid tolerance and supersensitivity induce regional changes in the autoradiographic density of dihydropyridine-sensitive calcium channels in the rat central nervous system.

Chronic opioid administration induces adaptations in neurones resulting in opioid tolerance and dependence. The changes in dihydropyridine (DHP)-sensitive Ca(2+) channels (L-type) associated with tolerance and supersensitivity to the antinociceptive effect of the micro-opioid receptor agonist sufentanil were analyzed in the central nervous system (CNS) of rats. Autoradiographic assays were performed with [(3)H]PN-200-110 (isopropyl 4-(2,1, 3-benzoxadiazol-4-yl)-1,4-dihydro-2, 6-dimethyl-5-methoxycarbonylpyridine-3-carboxylate). Chronic s.c. infusion of sufentanil (2 microg/h) for 7 days, which has been shown to induce tolerance to the opioid antinociceptive effect, produced an up-regulation of DHP binding sites. The highest increases in density were localized in regions involved in nociceptive transmission and perception, such as the dorsal horn of the spinal cord, the dorsal raphe nucleus, the central grey matter, the thalamic nuclei, and the somatosensory cortex. Animals were rendered supersensitive to the antinociceptive effect of sufentanil by chronic and simultaneous infusion of sufentanil (2 microg/h) and nimodipine (1 microg/h) for 7 days. Under these conditions, a greater increase in the number of DHP binding sites was observed in the spinal cord, central grey matter, dorsal raphe nucleus, and somatosensory neocortex, when compared to the sufentanil group. The role of an increased influx through L-type channels in opioid tolerance is reinforced, whereas their persistent blockade is essential for the expression of opioid supersensitivity.

Differential effects of environmental enrichment on behavior and learning of male and female Ts65Dn mice, a model for Down syndrome.

We have assessed the effects of enriched environment (EE) upon behavioral and cognitive performances of partially trisomic Ts65Dn (TS) mice and their control (CO) littermates. Enriched environment was applied to pups for 7 weeks after weaning. Circadian spontaneous activity (actimetry), exploratory behavior (hole board), activity in the open field and spatial memory (Morris Water Maze, repeated acquisition and cued paradigms) were analyzed in 86 female and 75 male mice, starting 15 days after completing enrichment. For each gender, mice were distributed in non-enriched and enriched control and trisomic groups. Enriched environment reduced in trisomic females and enhanced in trisomic males' circadian activity. Exploratory behavior was increased by enrichment in all groups, regardless of gender or presence of trisomy. In the Morris Water Maze, a significant improvement of the spatial memory was observed in enriched-control females, but not in enriched-control male mice, as assessed by distances traveled. Performances in the four groups of control animals were also consistently and significantly better than those of matching trisomic mice. In the acquisition trials, enrichment improved performance in trisomic female animals, but deteriorated in trisomic male mice. In all groups, changes in escape latencies and distances induced by enrichment were accounted for by changes in the total time spent in the periphery of the pool, indicating changes in learning strategy. Working memory was the function more affected by enrichment. It is concluded that enriched environment induces behavioral and learning changes in trisomic mice, although gender plays a significant modulatory role.

Overexpression of Dyrk1A is implicated in several cognitive, electrophysiological and neuromorphological alterations found in a mouse model of Down syndrome.

Down syndrome (DS) phenotypes result from the overexpression of several dosage-sensitive genes. The DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A) gene, which has been implicated in the behavioral and neuronal alterations that are characteristic of DS, plays a role in neuronal progenitor proliferation, neuronal differentiation and long-term potentiation (LTP) mechanisms that contribute to the cognitive deficits found in DS. The purpose of this study was to evaluate the effect of Dyrk1A overexpression on the behavioral and cognitive alterations in the Ts65Dn (TS) mouse model, which is the most commonly utilized mouse model of DS, as well as on several neuromorphological and electrophysiological properties proposed to underlie these deficits. In this study, we analyzed the phenotypic differences in the progeny obtained from crosses of TS females and heterozygous Dyrk1A (+/-) male mice. Our results revealed that normalization of the Dyrk1A copy number in TS mice improved working and reference memory based on the Morris water maze and contextual conditioning based on the fear conditioning test and rescued hippocampal LTP. Concomitant with these functional improvements, normalization of the Dyrk1A expression level in TS mice restored the proliferation and differentiation of hippocampal cells in the adult dentate gyrus (DG) and the density of GABAergic and glutamatergic synapse markers in the molecular layer of the hippocampus. However, normalization of the Dyrk1A gene dosage did not affect other structural (e.g., the density of mature hippocampal granule cells, the DG volume and the subgranular zone area) or behavioral (i.e., hyperactivity/attention) alterations found in the TS mouse. These results suggest that Dyrk1A overexpression is involved in some of the cognitive, electrophysiological and neuromorphological alterations, but not in the structural alterations found in DS, and suggest that pharmacological strategies targeting this gene may improve the treatment of DS-associated learning disabilities.

Los hermanos: la nueva era / No disponible

El autor, basándose en un reciente estudio de Cuskelly, reflexiona sobre las nuevas orientaciones que deben ser ofrecidas a los hermanos con síndrome de Down, ante las realidades de una nueva era. La vida de estas personas se ha prolongado notablemente, con todas sus consecuencias de diversos signos; las familias son más reducidas; los padres, de edad también más avanzada, muestran mayores limitaciones

The author relies on a recent research performed by Cuskelly on the intention to care of siblings of individuals with Down syndrome. The lives of these individuals have been prolonged and expanded in possibilities, offering consequences of different sign; the number of subjects in a family has been reduced; and the aged parents may not be capable to cope with these new challenges. New orientations should be offered to the siblings along these lines

Del conocimiento al servicio: conocer más para servir mejor / No disponible

Nuestro cerebro recibe la información que, gracias a la reflexión, se convierte y almacena en él en forma de conocimiento. De la mano del conocimiento el individuo opta por una determinada acción, decide. Esa opción viene condicionada por múltiples influencias, propias y externas. Es preciso incorporar e integrar la idea de servicio dentro de nuestros circuitos cerebrales, como argumento permanente en nuestra toma de decisiones. El mundo de la discapacidad ofrece un terreno especial para promover y cultivar la idea de servicio, llamada a manifestar los atributos trascendentales del ser humano: la verdad, la bondad y la belleza

Informative inputs reach the brain where, through reflection, are integrated and stored as knowledge. Knowledge leads to action that is individually selected, and consistently influenced by internal and external experiences. It becomes essential to include and integrate the concept and the reality of service into the cerebral circuits, in a way that it may permanently participate into the realm of decision-taking processes. The world of disability offers excellent opportunities to promote and develop the idea of service. It will help to make visible and to enlighten the transcendent attributes of human beings, namely the truth, the goodness and the beauty

El estudiante de medicina ante el síndrome de Down. Cuidados a las personas / No disponible

El cuidado a las personas con síndrome de Down parte de un principio fundamental: La esencia se asienta en que es un ser humano; lo accesorio es que tiene síndrome de Down. El cuidado a la persona exige contemplarla como tal: con sus necesidades y sus capacidades. Función indispensable de los médicos es el atender a la problemática médica mediante la aplicación de específicos programas de salud. El bienestar físico le ayudará a alcanzar el mayor bienestar psico-social. El taller analizará este programa, expondrá las modernas tareas educativas y psico-sociales, y dará oportunidad para que personas adultas con síndrome de Down muestren su realidad y experiencias

The care to individuals with Down syndrome should be based upon an essential principle: the person is a human being. Having Down syndrome is just an accidental element. Coping the care requires addressing the entire person, including both limitations and the abilities. The main function of the medical profession is to care for the physical health through the use of good health programs. The physical quality of life will help to secure the best psychosocial well-being. This workshop will offer and summarize, first, the health program; second, it will explain the current educational and psychosocial practices; third, it will give the opportunity to a lady with Down syndrome to show the highlights and experiences of her life

Neurodiversidad, discapacidad e inteligencias múltiples / No disponible

El autor rechaza la idea de sustituir el término de discapacidad por el de diversidad funcional, o el de discapacidad intelectual por el de neurodiversidad. Diversidad funcional y neurodiversidad son propiedades que definen a todo ser humano. Discapacidad intelectual, en cambio, queda definida por las limitaciones en las funciones cognitivas y conductas adaptativas que condicionan el funcionamiento en la vida diaria. En el desarrollo del cerebro humano se aprecian dos líneas fundamentales: la que es común a todos los individuos y define su condición humana, y la que es particular a cada uno y define sus cualidades personales e inteligencias múltiples. La neurociencia nos permite detectar y analizar los fallos en el desarrollo de estas dos líneas, que son el origen de la discapacidad intelectual, para poder elaborar los apoyos necesarios

The author holds that functional diversity cannot replace the concept of intellectual disability. Functional diversity is a condition that embraces all people. But intellectual disability is strictly defined by some dysfunction in both, cognitive functioning and adaptive behavior. In a similar vein, neurodiversity is a human quality embracing all individuals. Human brain is developed along two main lines: a common pathway that defines human condition, and an individual pathway which will account for personal qualities and multiple intelligences. Different and distinctive failures in the development and functioning of these two pathways in the brain will qualify and define each individual intellectual disability and its consequences. They are uncovered by the neuroscience, which will offer adequate solutions and support to the individual

Fundamentos de una terapéutica racional en el síndrome de Down / No disponible

El esperanzador futuro que se nos abre actualmente con la moderna farmacología de los estimulantes cognitivos en el síndrome de Down, cimentada en la experimentación con sus modelos animales, no nos debe ocultar la inmensa capacidad terapéutica aplicada en los últimos cuarenta años. Ella ha sido la responsable de los espectaculares avances conseguidos en el campo de la salud, la educación, la psicología, la conducta y, en conjunto, de la calidad de vida. Una mirada serena y objetiva nos permitirá asociar los mejores métodos, tanto educativos como farmacológicos, en beneficio de cada persona concreta

Advances in genetic and molecular techniques and the development of experimental models in animals have facilitated the development of new approaches and strategies for the treatment of some symptoms of Down syndrome. However, no less spectacular have been the advances attained in the educative and behavioral dimensions of the individuals with Down syndrome during the last forty years. The modern neuroscience provides insights to better apply a combination of both biological and psychological tools, to enhance cognition and behavior of the people with Down syndrome