TY - JOUR
T1 - Study of the Link Between Neuronal Death, Glial Response, and MAPK Pathway in Old Parkinsonian Mice
AU - Luisa Gil-Martinez, Ana
AU - Cuenca-Bermejo, Lorena
AU - Gallo-Soljancic, Pablo
AU - Sanchez-Rodrigo, Consuelo
AU - Izura, Virginia
AU - Steinbusch, Harry W. M.
AU - Fernandez-Villalba, Emiliano
AU - Trinidad Herrero, Maria
N1 - Funding Information:
This research work of the authors was supported by the Spanish Ministry of Science and Innovation (FIS PI13 01293), Fundación Séneca (19540/PI/14), and Nutrafur S.A. ‘‘Smartfoods and Cognition’’ (2015-2018, IDI20141212) to MH.
Funding Information:
Funding. This research work of the authors was supported by the Spanish Ministry of Science and Innovation (FIS PI13 01293), Fundaci?n S?neca (19540/PI/14), and Nutrafur S.A. ?Smartfoods and Cognition? (2015-2018, IDI20141212) to MH.
Publisher Copyright:
© Copyright © 2020 Gil-Martinez, Cuenca-Bermejo, Gallo-Soljancic, Sanchez-Rodrigo, Izura, Steinbusch, Fernandez-Villalba and Herrero.
PY - 2020/7/29
Y1 - 2020/7/29
N2 - Background: Parkinson's disease (PD) is described as an age-related neurodegenerative disorder. However, the vast majority of research is carried out using experimental models of young animals lacking the implications of the decline processes associated with aging. It has been suggested that several molecular pathways are involved in the perpetuation of the degeneration and the neuroinflammation in PD. Among others, mitogen-activated protein kinases (MAPKs) have been highly implicated in the development of PD, and regulating components of their activity are indicated as promising therapeutic targets. Methods: To further define how MAPKs expression is related to the glial response and neuronal cell death, Parkinsonism was induced under an acute regimen in old mice. Moreover, the sacrifice was carried out at different time points (4, 8, 24, and 48 h) after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) injections to describe the early dynamic changes over time produced by the intoxication. Results: The results revealed that neuronal death increases as glial response increases in the nigrostriatal pathway. It was observed that both processes increase from 4 h in the ventral mesencephalon (VM), and neuronal death becomes significant at 48 h. In the striatum, they were significantly increased from 48 h after the MPTP administration compared with that in the control mice. Moreover, the p-ERK levels decrease, while phospho-p38 expression increases specifically in the striatum at 48 h after MPTP intoxication. Conclusions: The importance of these data lies in the possibility of elucidating the underlying mechanisms of neurodegenerative processes under aging conditions to provide knowledge for the search of solutions that slow down the progression of PD.
AB - Background: Parkinson's disease (PD) is described as an age-related neurodegenerative disorder. However, the vast majority of research is carried out using experimental models of young animals lacking the implications of the decline processes associated with aging. It has been suggested that several molecular pathways are involved in the perpetuation of the degeneration and the neuroinflammation in PD. Among others, mitogen-activated protein kinases (MAPKs) have been highly implicated in the development of PD, and regulating components of their activity are indicated as promising therapeutic targets. Methods: To further define how MAPKs expression is related to the glial response and neuronal cell death, Parkinsonism was induced under an acute regimen in old mice. Moreover, the sacrifice was carried out at different time points (4, 8, 24, and 48 h) after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) injections to describe the early dynamic changes over time produced by the intoxication. Results: The results revealed that neuronal death increases as glial response increases in the nigrostriatal pathway. It was observed that both processes increase from 4 h in the ventral mesencephalon (VM), and neuronal death becomes significant at 48 h. In the striatum, they were significantly increased from 48 h after the MPTP administration compared with that in the control mice. Moreover, the p-ERK levels decrease, while phospho-p38 expression increases specifically in the striatum at 48 h after MPTP intoxication. Conclusions: The importance of these data lies in the possibility of elucidating the underlying mechanisms of neurodegenerative processes under aging conditions to provide knowledge for the search of solutions that slow down the progression of PD.
KW - ACTIVATION
KW - CONTRIBUTES
KW - DISEASE
KW - ERK
KW - MAPKs
KW - MONKEYS
KW - MPTP
KW - NEUROINFLAMMATION
KW - P38 MAPK
KW - Parkinsonism
KW - SUBSTANTIA-NIGRA
KW - aging
KW - neurodegeneration
KW - neuroinflammation
U2 - 10.3389/fnagi.2020.00214
DO - 10.3389/fnagi.2020.00214
M3 - Article
C2 - 32848701
SN - 1663-4365
VL - 12
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
M1 - 214
ER -