Sobrecarga del cuidador y distrofia miotónica de Steinert tipo 1 / Caregiver overload and Steinert myotonic dystrophy type 1

Introducción: La distrofia miotónica tipo 1 es la distrofia muscular más frecuente a nivel mundial. Progresa lentamente llevando al paciente a la pérdida de autonomía lo que implica la necesidad del cuidador, quien con frecuencia, también padece la enfermedad. El síndrome de sobrecarga, desgaste o burnout, término en inglés muy utilizado en la bibliografía médica, se ha descrito en los últimos años para los cuidadores y es el desgaste emocional una de sus particularidades. Objetivo: Evaluar la autonomía para la realización de actividades diarias de los pacientes con distrofia miotónica tipo 1 en referencia al tiempo de evolución de la enfermedad y determinar la magnitud de desgaste en los cuidadores. Metodología: Se aplicó la escala de autonomía de Barthel a 29 pacientes y el cuestionario de Maslach a sus cuidadores. Resultados: Se demostró que las mujeres cuidadoras resultaron más afectadas en el intercambio con el enfermo para el cuidado, en la subescala despersonalización del instrumento Maslach (U de Mann-Whitney p = 0,05). Conclusiones: Se sugiere que los cuidadores femeninos son el grupo de mayor riesgo de padecer el síndrome de sobrecarga(AU)

Introduction: Myotonic dystrophy type 1 is the most common muscular dystrophy worldwide. It progresses slowly, depriving patients of their autonomy, which implies the need for a caregiver, who would often suffer from the disease as well. The overload or burnout syndrome, an English term very often found in medical bibliography, has been described for caregivers in recent years, and emotional wear is one of its features. Objective: Evaluate the autonomy to perform activities of daily living of patients with myotonic dystrophy type 1 with reference to the time of evolution of the disease, and determine the extent of wear in caregivers. Methods: A study of a clinical case series was conducted for two years at the Institute of Neurology and Neurosurgery in Havana. Patients were evaluated with the Barthel autonomy scale and caregivers with the Maslach burnout syndrome inventory. Inclusion criteria admitted patients of both sexes clinically and neurophysiologically characterized for this diagnosis. It was also required to obtain the informed consent of patients and caregivers responding to the overload measuring tool. Exclusion criteria left out patients with a dystrophic condition other than Steinert type 1, inconclusive clinical and electromyographic evaluations, or not willing to participate in the study. Results: According to the depersonalization subscale in the Maslach tool (Mann-Whitney U p = 0.05), female caregivers are more often affected by the interaction with the person cared for. Conclusions: Results suggest that female caregivers are under a greater risk of overload syndrome(AU)

Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus.

A need for new antidepressants is necessary since traditional antidepressants have several flaws. Neuropeptide Y(NPY) Y1 receptor (NPYY1R) and galanin (GAL) receptor 2 (GALR2) interact in several regions of the limbic system, including the hippocampus. The current study assesses the antidepressant effects induced by GALR2 and NPYY1R coactivation, together with the evaluation of cell proliferation through 5-Bromo-2'-deoxyuridine expression within the dentate gyrus of the ventral hippocampus (vDG). We employed in situ proximity ligation assay to manifest GALR2/NPYY1R heteroreceptor complexes. Additionally, the expression pattern of GALR2 and the activation of the extracellular-regulated kinases (ERK) pathway after GALR2 and NPYY1R costimulation in cell cultures were examined. GALR2 and NPYY1R coactivation resulted in sustained antidepressant behaviors in the FST after 24 h, linked to increased cell proliferation in the vDG. Moreover, an increased density of GALR2/NPYY1R heteroreceptor complexes was observed in vDG, on doublecortin-expressing neuroblasts. Recruitment of the GALR2 expression to the plasma membrane was observed upon the coactivation of GALR2 and NPYY1R in cell cultures, presumably associated to the enhanced effects on the activation of ERK pathway. GALR2 may promote the GALR2/NPYY1R heteroreceptor complexes formation in the ventral hippocampus. It may induce a transformation of cell proliferation toward a neuronal lineage by enhancement of ERK pathway. Thus, it may give the mechanism for the antidepressant behavior observed. These results may provide the basis for the development of heterobivalent agonist pharmacophores, targeting GALR2/NPYY1R heteromers, especially in the neuronal precursor cells of the dentate gyrus in the ventral hippocampus for the novel treatment of depression.

Evidence for the existence of A2AR-TrkB heteroreceptor complexes in the dorsal hippocampus of the rat brain: Potential implications of A2AR and TrkB interplay upon ageing.

Adenosine A2A receptors (A2AR) are crucial in facilitating the BDNF action on synaptic transmission in the rat hippocampus primarily upon ageing. Furthermore, it has been suggested that A2AR-Tropomyosin related kinase B receptor (TrkB) crosstalk has a pivotal role in adenosine A2AR-mediated modulation of the BDNF action on hippocampal plasticity. Considering the impact of the above receptors interplay on what concerns BDNF-induced enhancement of synaptic transmission, gaining a better insight into the mechanisms behind this powerful crosstalk becomes of primary interest. Using in situ proximity ligation assay (PLA), the existence of a direct physical interaction between adenosine A2AR and TrkB is demonstrated. The A2AR-TrkB heteroreceptor complexes show a heterogeneous distribution within the rat dorsal hippocampus. High densities of the heteroreceptor complexes were observed in the pyramidal cell layers of CA1-CA3 regions and in the polymorphic layer of the dentate gyrus (DG). The stratum radiatum of the CA1-3 regions showed positive PLA signal in contrast to the oriens region. The molecular and granular layers of the DG also lacked significant densities of PLA positive heteroreceptor complexes, but subgranular zone showed some PLA positive cells. Their allosteric receptor-receptor interactions may significantly modulate BDNF signaling impacting on hippocampal plasticity which is impaired upon ageing.

Comparison of the clinical and genetic features of amyotrophic lateral sclerosis across Cuban, Uruguayan and Irish clinic-based populations.

OBJECTIVES: This study compares the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) within three clinic-based populations from Cuba, Uruguay and Ireland and determines the impact of known ALS-associated genetic variants on phenotypic manifestations within the Cuban population. METHODS: Demographic and clinical information was collected on 115 Cuban, 220 Uruguayan and 1038 Irish patients with ALS attending national specialist clinics through 1996-2017. All Cuban patients and 676 Irish patients underwent next-generation DNA sequencing and were screened for the pathogenic C9orf72 repeat expansion. RESULTS: The mean age of onset was younger in the Cuban (53.0 years, 95% CI 50.4 to 55.6) and Uruguayan (58.2 years, 95% CI 56.5 to 60.0) populations compared with the Irish population (61.6 years, 95% CI 60.9 to 62.4). No differences in survival between populations were observed. 1.7 % (95% CI 0.6 to 4.1) of Cubans with ALS carried the C9orf72 repeat expansion compared with 9.9% (95% CI 7.8 to 12.0) of Irish patients with ALS (p=0.004). Other known variants identified in the Cuban population included ANG (one patient), CHCHD10 (one patient) and DCTN1 (three patients). CONCLUSIONS AND RELEVANCE: This study is the first to describe the clinical characteristics of ALS in Cuban and Uruguayan populations and report differences between the Cuban and Irish genetic signature in terms of known ALS-associated genetic variants. These novel clinical and genetic data add to our understanding of ALS across different and understudied populations.