TY - JOUR
T1 - Characterization of the antiapoptotic effect of copper sulfate on striatal and midbrain damage induced by MPP+ in rats
AU - Islas-Cortez, Marcela
AU - Rios, Camilo
AU - Rubio-Osornio, Moisés
AU - Zamudio, Sergio
AU - Orozco-Suarez, Sandra
AU - Mendez-Armenta, Marisela
AU - Nava-Ruiz, Concepción
AU - Diaz-Ruiz, Araceli
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/1
Y1 - 2021/1
N2 - 1-Methyl-4-phenylpyridinium ion (MPP+)-induced neurotoxicity produces cellular damage resembling that encountered in Parkinson's disease. The mechanisms of cellular death after MPP+ include the participation of oxidative stress in the loss of dopaminergic neurons. Among the mechanisms of defense against oxidative stress, several copper-dependent proteins have been implicated: Cu/Zn-SOD, ceruloplasmin, and metallothionein. Another important mechanism of damage, is MPP + interference with mitochondrial respiration. Both, oxidative stress and inhibition of mitochondrial respiration may trigger apoptosis in the neurons after MPP+. The aim of the present study was to characterize the time-course of apoptosis induced by MPP+ to determine if copper sulfate pretreatment is able to prevent the activation of caspases and decreased the neuronal apoptosis. MPP+ was microinjected into rat striatum using a stereotactic frame. The results showed increased activities of caspases 8, 9 and 3, between 72–120 hours after administration of MPP+, both in striatum and midbrain. After this study, we tested the effect of CuSO4 on MPP+ neurotoxicity, showing a diminution of the apoptotic damage induced by MPP+, decreased levels of enzymatic activity of caspases: 8 (-34 and -25 %), 9 (-25 and -42 %) and 3 (-40 and -29 %) in striatum and midbrain, respectively. Finally, we performed an immunohistochemical analysis, evidencing a decreased number of apoptotic cells in the groups pretreated with copper sulfate pretreatment compared to the control group. With these findings, it is concluded that pretreatment with copper sulfate may be a good alternative to prevent MPP+-induced apoptosis.
AB - 1-Methyl-4-phenylpyridinium ion (MPP+)-induced neurotoxicity produces cellular damage resembling that encountered in Parkinson's disease. The mechanisms of cellular death after MPP+ include the participation of oxidative stress in the loss of dopaminergic neurons. Among the mechanisms of defense against oxidative stress, several copper-dependent proteins have been implicated: Cu/Zn-SOD, ceruloplasmin, and metallothionein. Another important mechanism of damage, is MPP + interference with mitochondrial respiration. Both, oxidative stress and inhibition of mitochondrial respiration may trigger apoptosis in the neurons after MPP+. The aim of the present study was to characterize the time-course of apoptosis induced by MPP+ to determine if copper sulfate pretreatment is able to prevent the activation of caspases and decreased the neuronal apoptosis. MPP+ was microinjected into rat striatum using a stereotactic frame. The results showed increased activities of caspases 8, 9 and 3, between 72–120 hours after administration of MPP+, both in striatum and midbrain. After this study, we tested the effect of CuSO4 on MPP+ neurotoxicity, showing a diminution of the apoptotic damage induced by MPP+, decreased levels of enzymatic activity of caspases: 8 (-34 and -25 %), 9 (-25 and -42 %) and 3 (-40 and -29 %) in striatum and midbrain, respectively. Finally, we performed an immunohistochemical analysis, evidencing a decreased number of apoptotic cells in the groups pretreated with copper sulfate pretreatment compared to the control group. With these findings, it is concluded that pretreatment with copper sulfate may be a good alternative to prevent MPP+-induced apoptosis.
KW - Apoptosis
KW - Copper
KW - MPP
KW - Parkinson Disease Model
UR - http://www.scopus.com/inward/record.url?scp=85096226890&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2020.10.011
DO - 10.1016/j.neuro.2020.10.011
M3 - Artículo
C2 - 33127410
AN - SCOPUS:85096226890
SN - 0161-813X
VL - 82
SP - 18
EP - 25
JO - NeuroToxicology
JF - NeuroToxicology
ER -