Nuevos modelos transgénicos para el estudio de la enfermedad de Parkinson basados en sistemas de edición con nucleasas / New transgenic models of Parkinson's disease using genome editing technology

INTRODUCCIÓN: La enfermedad de Parkinson (EP) es el segundo trastorno neurodegenerativo más común, caracterizado por la pérdida selectiva de neuronas dopaminérgicas en la substancia nigra pars compacta, produciendo depleción en los niveles de dopamina y dando como resultado las manifestaciones clínicas de la enfermedad que se pueden clasificar como síntomas motrices y no motrices. DESARROLLO: En los últimos años, la generación de nuevos modelos animales basados en los sistemas de edición genética por nucleasas: ZFN, TALEN, CRISPR/Cas9, permiten la realización de modificaciones personalizadas en el genoma, replicando características clave que definen a la EP y consecuentemente avances significativos en la comprensión del proceso fisiopatológico de este trastorno. CONCLUSIÓN: En esta revisión recopilamos los estudios más novedosos de esta nueva generación de modelos in vitro e in vivo de la EP que permiten emular síntomas clave y tener una mayor comprensión de la etiología o los mecanismos involucrados en el proceso de iniciación o desarrollo de la enfermedad y la futura prueba de terapias realmente eficaces para detener o ralentizar su progresión

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterised by selective loss of dopaminergic neurons in the substantia nigra pars compacta, which results in dopamine depletion, leading to a number of motor and non-motor symptoms. DEVELOPMENT: In recent years, the development of new animal models using nuclease-based genome-editing technology (ZFN, TALEN, and CRISPR/Cas9 nucleases) has enabled the introduction of custom-made modifications into the genome to replicate key features of PD, leading to significant advances in our understanding of the pathophysiology of the disease. CONCLUSIONS: We review the most recent studies on this new generation of in vitro and in vivo PD models, which replicate the most relevant symptoms of the disease and enable better understanding of the aetiology and mechanisms of PD. This may be helpful in the future development of effective treatments to halt or slow disease progression

La eritropoyetina humana recombinante reduce la disfunción sensoriomotora y el deterioro cognitivo en ratas con enfermedad renal crónica / Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease

INTRODUCCIÓN: La enfermedad renal crónica (ERC) puede provocar anemia e inducir afectaciones neurológicas. La eritropoyetina humana recombinante (rHuEPO) se utiliza en el tratamiento de la anemia en la ERC. Sin embargo, existe poca evidencia de los efectos de la rHuEPO sobre la conducta y las funciones cognitivas en la ERC. El objetivo de este estudio fue evaluar el efecto del tratamiento con rHuEPO sobre las funciones sensoriomotoras y cognitivas en un modelo de ERC. MÉTODOS: Ratas macho de la cepa Wistar fueron asignadas a 4 grupos: control y ERC, con y sin tratamiento con rHuEPO (1.050 UI/kg de peso, una vez por semana durante 4 semanas). Las pruebas conductuales de laberinto acuático de Morris, campo abierto y cinta adhesiva se realizaron de manera simultánea a la inducción del daño renal y el tratamiento. Mientras que la determinación de marcadores de función renal y anemia se realizaron al término del estudio. RESULTADOS: El tratamiento con rHuEPO redujo el daño en el riñón y corrigió la anemia en las ratas con ERC. En las pruebas conductuales, el tratamiento con rHuEPO redujo la disfunción sensoriomotora observada en los animales con ERC. Por otra parte, en los animales con ERC y tratamiento con rHuEPO resolvieron el laberinto en menor tiempo en comparación a los grupos control. CONCLUSIONES: El tratamiento con rHuEPO reduce el daño en el riñón, corrige la anemia y reduce la disfunción sensoriomotora y cognitiva en los animales con ERC

INTRODUCTION: Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. METHODS: Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. RESULTS: Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. CONCLUSIONS: rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD

Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease. / La eritropoyetina humana recombinante reduce la disfunción sensoriomotora y el deterioro cognitivo en ratas con enfermedad renal crónica.

INTRODUCTION: Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. METHODS: Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. RESULTS: Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. CONCLUSIONS: rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD.

New transgenic models of Parkinson's disease using genome editing technology. / Nuevos modelos transgénicos para el estudio de la enfermedad de Parkinson basados en sistemas de edición con nucleasas.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterised by selective loss of dopaminergic neurons in the substantia nigra pars compacta, which results in dopamine depletion, leading to a number of motor and non-motor symptoms. DEVELOPMENT: In recent years, the development of new animal models using nuclease-based genome-editing technology (ZFN, TALEN, and CRISPR/Cas9 nucleases) has enabled the introduction of custom-made modifications into the genome to replicate key features of PD, leading to significant advances in our understanding of the pathophysiology of the disease. CONCLUSIONS: We review the most recent studies on this new generation of in vitro and in vivo PD models, which replicate the most relevant symptoms of the disease and enable better understanding of the aetiology and mechanisms of PD. This may be helpful in the future development of effective treatments to halt or slow disease progression.

Efecto neuroprotector de fitoquímicos en cultivo de neuronas dopaminérgicas / Neuroprotective effects of phytochemicals on dopaminergic neuron cultures

Introducción: La enfermedad de Parkinson es un trastorno neurodegenerativo progresivo caracterizado por la pérdida de neuronas dopaminérgicas de la sustancia nigra pars compacta, promoviendo una disminución significativa en los niveles de dopamina y en consecuencia el deterioro funcional del circuito motor. Desarrollo: Aunque su etiología no está bien esclarecida, se han propuesto varios mecanismos patogénicos, entre ellos destaca el estrés oxidativo. La terapia actual se basa en medicamentos que reemplazan la dopamina, sin embargo, no son capaces de detener o incluso ralentizar la progresión de la enfermedad. En la actualidad están siendo investigados nuevos enfoques terapéuticos con la intención de influir en las vías que conducen a la disfunción y muerte neuronal. Conclusiones: En los últimos años, se ha evidenciado el efecto neuroprotector de moléculas naturales debido a sus propiedades antioxidantes y antiinflamatorias dentro de los cuales destacan los polifenoles, los alcaloides y las saponinas. El objetivo de esta revisión es recopilar los estudios más importantes a nivel mundial que establecen las propiedades benéficas de algunos fitoquímicos utilizados en modelos in vitro de la enfermedad de Parkinson

Introduction. Parkinson's disease is a progressive neurodegenerative disorder characterised by a loss of dopaminergic neurons in the substantia nigra pars compacta, which results in a significant decrease in dopamine levels and consequent functional motor impairment. Development: Although its aetiology is not fully understood, several pathogenic mechanisms, including oxidative stress, have been proposed. Current therapeutic approaches are based on dopamine replacement drugs; these agents, however, are not able to stop or even slow disease progression. Novel therapeutic approaches aimed at acting on the pathways leading to neuronal dysfunction and death are under investigation. Conclusions: In recent years, such natural molecules as polyphenols, alkaloids, and saponins have been shown to have a neuroprotective effect due to their antioxidant and anti-inflammatory properties. The aim of our review is to analyse the most relevant studies worldwide addressing the benefits of some phytochemicals used in in vitro models of Parkinson's disease

Neuroprotective effects of phytochemicals on dopaminergic neuron cultures. / Efecto neuroprotector de fitoquímicos en cultivo de neuronas dopaminérgicas.

INTRODUCTION: Parkinson's disease is a progressive neurodegenerative disorder characterised by a loss of dopaminergic neurons in the substantia nigra pars compacta, which results in a significant decrease in dopamine levels and consequent functional motor impairment. DEVELOPMENT: Although its aetiology is not fully understood, several pathogenic mechanisms, including oxidative stress, have been proposed. Current therapeutic approaches are based on dopamine replacement drugs; these agents, however, are not able to stop or even slow disease progression. Novel therapeutic approaches aimed at acting on the pathways leading to neuronal dysfunction and death are under investigation. CONCLUSIONS: In recent years, such natural molecules as polyphenols, alkaloids, and saponins have been shown to have a neuroprotective effect due to their antioxidant and anti-inflammatory properties. The aim of our review is to analyse the most relevant studies worldwide addressing the benefits of some phytochemicals used in in vitro models of Parkinson's disease.