Individual differences in the forced swimming test and the effect of environmental enrichment: searching for an interaction.

Animals with low and high immobility in the forced swimming test (FST) differ in a number of neurobehavioral factors. A growing body of evidence suggests that the exposure to enriched environments mediates a number of changes in the brain. Therefore, we studied if animals' individuality can somehow modulate the response to environmental stimuli. Male rats were classified according to their immobility time scores in the FST test session as animals with low, medium or high immobility. Then, rats from groups with low and high immobility were randomly distributed in two groups to be reared in different housing conditions (i.e., enriched and standard conditions) during 8weeks. Animals were subjected to the open field test (OFT) before and 6weeks after the start of housing protocol. Rats with high immobility in the FST also showed high ambulation and high rearing time in the first OFT. Such findings were not observed in the second OFT. Conversely, an effect of environmental enrichment was found in the second OFT where enriched animals showed lower ambulation and higher grooming time than the standard control group. Rats were sacrificed after the housing protocol and neurochemical content and/or gene expression were studied in three different brain regions: the prefrontal cortex, the hippocampus and the nucleus accumbens. Rats with low immobility showed significantly higher accumbal 5-HT levels than animals with high immobility, whereas no neurochemical differences were observed between enriched and standard animals. Regarding expression data, however, an effect of enrichment on accumbal corticotropin-releasing factor (CRF) and its receptor 1 (CRFR1) levels was observed, and such effect depended on immobility levels. Thus, our results not only allowed us to identify a number of differences between animals with low and high immobility or animals housed in standard and enriched conditions, but also suggested that animals' individuality modulated in some way the response to environmental stimuli.

[Neurodevelopmental (fragile X syndrome) and neurodegenerative (tremor/ataxia syndrome) disorders associated to the 'growth' of a gene]. / Trastornos del neurodesarrollo (síndrome X frágil) y neurodegenerativos (síndrome de temblor/ataxia) asociados al 'crecimiento' de un gen.

AIM: To present the latest findings on fragile X syndrome, the first genetic disorder identified to be caused by a new type of mutation called trinucleotide repeat expansion. DEVELOPMENT: Fragile X syndrome is the most common form of inherited mental retardation, is caused by hyperexpansion and hypermethylation of a CGG repeat tract in the FMR1 gene. In the first section we will discuss the various aspects of the gene mutation and the gene product, its phenotypic consequences in mutation carriers, diagnostic methodology, epidemiology, prevention, treatment and situation in Costa Rica. The second section deals with the recent findings in relation to the very recently described fragile X premutation tremor/ataxia syndrome, a neurodegenerative disorder affecting carriers of the mutation. CONCLUSIONS: Screening for the gene premutation in aged individuals who have tremor and balance problems is important, especially when accompanied by other signs such as parkinsonism, short term memory loss and dementia. Family genetic counselling can help those affected as well as future generations which may inherit fragile X syndrome.

Trastornos del neurodesarrollo (síndrome X frágil) y neurodegenerativos (síndrome de temblor/ataxia) asociados al 'crecimiento' de un gen / Neurodevelopmental (fragile X syndrome) and neurodegenerative (tremor/ataxia syndrome) disorders associated to the 'growth' of a gene

Objetivos. Presentar los últimos hallazgos acerca del síndrome del cromosoma X frágil, el primer trastorno genético identificado causado por un nuevo tipo de mutación llamado expansión de trinucleótidos repetidos. Desarrollo. El síndrome del cromosoma X frágil es la causa más común de retraso mental hereditario; lo causa el aumento de la expansión y de la metilación de un segmento de repeticiones CGG en el gen FMR1. En la primera sección discutiremos varios aspectos de la mutación y del producto génico, sus consecuencias fenotípicas en los afectados con la mutación, la metodología diagnóstica, la epidemiología, la prevención, el tratamiento y la situación en Costa Rica. En la segunda sección nos referiremos al recientemente descrito síndrome premutación X frágil con temblor/ataxia, un trastorno neurodegenerativo que afecta a los portadores de la mutación. Conclusiones. Es importante hacer una criba de la premutación del gen en adultos mayores con temblor y problemas de equilibrio, especialmente cuando se acompaña de otros signos como parkinsonismo, pérdida de memoria y demencia. El asesoramiento genético a la familia puede ser útil para los afectados y para las generaciones futuras que pueden heredar el síndrome del cromosoma X frágil

Aim. To present the latest findings on fragile X syndrome, the first genetic disorder identified to be caused by a new type of mutation called trinucleotide repeat expansion. Development. Fragile X syndrome is the most common form of inherited mental retardation, is caused by hyperexpansion and hypermethylation of a CGG repeat tract in the FMR1 gene. In the first section we will discuss the various aspects of the gene mutation and the gene product, its phenotypic consequences in mutation carriers, diagnostic methodology, epidemiology, prevention, treatment and situation in Costa Rica. The second section deals with the recent findings in relation to the very recently described fragile X premutation tremor/ataxia syndrome, a neurodegenerative disorder affecting carriers of the mutation. Conclusions. Screening for the gene premutation in aged individuals who have tremor and balance problems is important, especially when accompanied by other signs such as parkinsonism, short term memory loss and dementia. Family genetic counselling can help those affected as well as future generations which may inherit fragile X syndrome

[Molecular and genetic aspects of the myotonic conditions]. / Aspectos geneticos y moleculares de las enfermedades miotonicas.

AIM: The aim is to review the molecular and genetic aspects of the dystrophic and no dystrophic myotonias. BACKGROUND: Myotonic diseases are hereditary conditions of the skeletal muscle, classified in two groups depending on the symptoms. In the first group are the myotonic dystrophies, with the myotonic dystrophies type 1 and 2. In the second group are the channelopathies, characterized for the affected function of the ion channels. Myotonic dystrophy type 1, a neurodegenerative, progressive and disabling disease is caused by an expansion of the CTG trinucleotide, its size shows a positive correlation with the severity and negative with age of onset. There are enough insights to think that the gain of function of the mutant ARN is the pathophysiological mechanism occurring on this disease. Myotonic dystrophy type 2, less severe than type 1, is caused by an expansion of the CCTG tetranucleotide, its pathophysiological mechanism is similar to that one proposed for the type 1. In the second group we can find the chloride channelopathies, with autosomal dominant or recessive inheritance, caused by one of the 60 different mutations on the chloride channel gene; and the sodium channelopathies, group of three clinically overlapping diseases, with dominant heredity caused by one of the 25 different mutations on the sodium channel gene. CONCLUSIONS: These diseases are highly clinically variable, and even though their genetic base is known, it is necessary too much research in order to understand their pathophisiology and the phenotype genotype relationships.

Aspectos genéticos y moleculares de las enfermedades miotónicas / Molecular and genetic aspects of the myotonic conditions

Objetivo. Revisar los aspectos genéticos y moleculares de las miotonías distróficas y no distróficas. Desarrollo. Las enfermedades miotónicas son condiciones hereditarias del músculo esquelético, las cuales se pueden clasificar en dos grupos según el cuadro clínico. Al primer grupo pertenecen las miotonías distróficas, donde se encuentran las distrofias miotónicas (DM) tipo 1 y 2.Al segundo grupo pertenecen las canalopatías, que se caracterizan por presentar alteraciones de la función en los canales iónicos. La DM tipo 1, enfermedad neurodegenerativa, progresiva y discapacitante, la causa una expansión del trinucleótido CTG, cuyo tamaño muestra correlación positiva con la gravedad y negativa con la edad de manifestación. Existe evidencia suficiente para pensar que el mecanismo fisiopatológico de la enfermedad es la ganancia de función del ARN mutado. La DM tipo 2, menos grave que la tipo 1, la causa una expansión del tetranucleótido CCTG, cuyo mecanismo fisiopatológico es similar al propuesto para la tipo 1. En el segundo grupo se encuentran las canalopatías de cloruro, de herencia autosómica dominante o recesiva, causadas por una de las 60 diferentes mutaciones en el gen del canal de cloruro, y las canalopatías de sodio, grupo de tres enfermedades que se solapan clínicamente, de herencia dominante, causadas por una de las 25 diferentes mutaciones en el gen del canal de sodio. Conclusiones. Estas enfermedades son clínicamente muy variables; no obstante, su base genética se conoce; falta todavía mucha investigación para lograr entender su fisiopatología y las relaciones genotipo-fenotipo (AU)

[Intergenerational study of the mutation that causes Myotonic Dystrophy Type 1 in Costa Rica]. / Estudio intergeneracional de la mutación que causa la distrofia miotónica tipo 1 en Costa Rica.

INTRODUCTION: Myotonic dystrophy type 1 is a neuromuscular, degenerative and progressive disease, with an autosomal dominant pattern of inheritance, variable expressivity and incomplete penetrance. The genetic defect is an unstable mutation due to the expansion of the triplet CTG in the 3 unstranslated region at the DMPK gene on chromosome 19q13.3. OBJECTIVE: The main objective was to study the intergenerational behavior of the DM1 mutation in order to evaluate the importance of this disease as a neurological problem that could be manageable by genetic counseling. PATIENTS AND METHODS: The study involved 84 patients with clinical diagnosis of DM1 and their relatives, which were confirmed through molecular diagnosis using Southern blot and PCR. RESULTS: Data analysis reveals the size of the mutation presents a positive correlation with the severity of the symptoms and a negative correlation with the age of onset. Transmission of the DM1 mutation is sex and size dependent among the Costa Rican patients. There is an important increment in the size of the mutation between generations and there are no differences in mutation size respect to the transmitting sex. CONCLUSION: The worldwide intergenerational behavior of the DM1 mutation is similar in Costa Rica