Publication: Melatonin prevents dopaminergic
cell loss induced by lentiviral vectors
expressing A30P mutant alpha-synuclein
Authors
Brito-Armas, J.M. ; Baekelandt, V. ; Castro-Hernández, J.R. ; González-Hernández, T. ; Rodríguez, M. ; Castro Fuentes, Rafael
item.page.secondaryauthor
item.page.director
Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
publication.page.editor
publication.page.department
DOI
item.page.type
info:eu-repo/semantics/article
Description
Abstract
Two hallmarks of Parkinson’s disease (PD)
are dopaminergic cell loss and the presence of
cytoplasmic inclusions (Lewy bodies). Different point
mutations in alpha-synuclein, the main constituent of
Lewy bodies, have been identified in familial PD.
Alpha-synuclein also constitutes one of the main
components of Lewy bodies in sporadic cases of PD.
Moreover, oxidant stress and generation of free radicals
from both mitochondrial impairment and dopamine
metabolism are considered to play critical roles in PD
etiopathogenesis. Melatonin, a known potent antioxidant
secreted by the pineal gland, may protect against the
effect of several Parkinsonogenic compounds that are
associated with progressive impairment of mitochondrial
function and increased oxidative damage. However, the
neuroprotective effect of melatonin has never been tested
in the newly available genetic models of PD based on
the viral expression of mutated alpha-synuclein.
Lentiviral vectors encoding A30P mutant human alphasynuclein
(lenti-A30P) were stereotactically injected into
the right substantia nigra of adult male Sprague-Dawley
rats and neuroprotection was examined by
administration of melatonin or vehicle from two days
before nigral administration of lenti-A30P until eight
weeks after injection. It was found that lenti-A30P
induced a significant TH+ cell-loss both in the medial
and lateral substantia nigra versus the contrallateral side
injected with lenti-eGFP. However, melatonin administration showed a total neuroprotective effect in
both regions of the substantia nigra. In conclusion, the
data here show that melatonin is neuroprotective against
mutant alpha-synuclein-induced injury in the substantia
nigra.
publication.page.subject
Citation
Histology and Histopathology, vol. 28, nº 8 (2013)
item.page.embargo
Ir a Estadísticas
Sin licencia Creative Commons.