Chronic and progressive Parkinson's disease MPTP model in adult and aged mice.
Despite the different animal models of Parkinson's disease developed during the last years, they still present limitations modelling the slow and progressive process of neurodegeneration. Here, we undertook a histological, neurochemical and behavioural analysis of a new chronic parkinsonian mouse model generated by the subcutaneous administration of low doses of MPTP (20 mg/kg, 3 times per week) for 3 months, using both young adult and aged mice. The MPTP-induced nigrostriatal neurodegeneration was progressive and was accompanied by a decrease in striatal dopamine levels and motor impairment. We also demonstrated the characteristic neuroinflammatory changes (microglial activation and astrogliosis) associated with the neurodegenerative process. Aged animals showed both a faster time course of neurodegeneration and an altered neuroinflammatory response. The long-term systemic application of low MPTP doses did not induce any increase in mortality in either young adult or aged mice and better resembles the slow evolution of the neurodegenerative process. This treatment could be useful to model different stages of Parkinson's disease, providing a better understanding of the pathophysiology of the disease and facilitating the testing of both protective and restorative treatments. Here, we show a new chronic and progressive parkinsonian mouse model, in young and aged mice. This model produces a stable degeneration of the dopaminergic nigrostriatal pathway, continuous neuroinflammatory reaction and motor deficits. Aged animals showed a faster neurodegeneration and an altered neuroinflammatory response. This treatment could be useful to model different stages of PD and to test both protective and restorative therapeutic approaches.
Instituto de Biomedicina de Sevilla-IBiS, HUVR/Universidad de Sevilla/CSIC, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
Ana B
AB
Muñoz-Manchado
Instituto de Biomedicina de Sevilla-IBiS, HUVR/Universidad de Sevilla/CSIC, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
Javier
J
Villadiego
Instituto de Biomedicina de Sevilla-IBiS, HUVR/Universidad de Sevilla/CSIC, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
Sonia
S
Romo-Madero
Instituto de Biomedicina de Sevilla-IBiS, HUVR/Universidad de Sevilla/CSIC, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
Nela
N
Suárez-Luna
Instituto de Biomedicina de Sevilla-IBiS, HUVR/Universidad de Sevilla/CSIC, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
Alfonso
A
Bermejo-Navas
Instituto de Biomedicina de Sevilla-IBiS, HUVR/Universidad de Sevilla/CSIC, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
José A
JA
Rodríguez-Gómez
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.|Departamento de Ciencias Morfológicas, Universidad de Santiago de Compostela, CIMUS, Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain.
Pablo
P
Garrido-Gil
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.|Departamento de Ciencias Morfológicas, Universidad de Santiago de Compostela, CIMUS, Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain.
José L
JL
Labandeira-García
Instituto de Biomedicina de Sevilla-IBiS, HUVR/Universidad de Sevilla/CSIC, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
Miriam
M
Echevarría
Instituto de Biomedicina de Sevilla-IBiS, HUVR/Universidad de Sevilla/CSIC, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
José
J
López-Barneo
Instituto de Biomedicina de Sevilla-IBiS, HUVR/Universidad de Sevilla/CSIC, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
Juan J
JJ
Toledo-Aral
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000367:Age Factors; D000375:Aging; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002908:Chronic Disease; D003342:Corpus Striatum / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000209:etiology; D020267:MPTP Poisoning / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D009410:Nerve Degeneration / Q000209:etiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D009419:Nerve Tissue Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase
MPTP; Parkinson's disease; ageing; animal models; dopamine; neuroinflammation