Minocycline inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after treatment with kainic acid in mice.
Although minocycline has been generally thought to have neuroprotective properties, the neuroprotective role of minocycline has not been investigated in the animal model of epilepsy. In this study, we investigated whether minocycline is neuroprotective against kainic acid (KA)-induced cell death through the caspase-dependent or -independent mitochondrial apoptotic pathways. Adult male ICR mice were subjected to seizures by intrahippocampal KA injection with vehicle or with minocycline. For cell death analysis, TdT-mediated dUTP-biotin nick end labeling and cresyl-violet staining were performed. Western blot analysis and immunofluorescent staining for cytochrome c and apoptosis-inducing factor (AIF) were performed. Cell death was reduced in minocycline-treated mice. Cytosolic translocation of cytochrome c and subsequent activation of caspase-3 were diminished by minocycline treatment. AIF nuclear translocation and subsequent large-scale DNA fragmentation were also reduced in minocycline-treated mice. Thus, this study suggests that minocycline inhibits both caspase-dependent and -independent apoptotic pathways and may be neuroprotective against hippocampal damage after KA treatment.
Department of Neurology and Brain Korea 21 Project for Medical Science, Yonsei University, College of Medicine, 134 Sinchon-dong, Seodaemun-gu, 120-752 Seoul, Republic of Korea.
Kyoung
K
Heo
Yang-Je
YJ
Cho
Kyoung-Joo
KJ
Cho
Hyun-Woo
HW
Kim
Hyun-Jung
HJ
Kim
Ha Young
HY
Shin
Byung In
BI
Lee
Gyung Whan
GW
Kim
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008911:Minocycline / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*
D051033:Apoptosis Inducing Factor; D018696:Neuroprotective Agents; D045304:Cytochromes c; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D008911:Minocycline; D007608:Kainic Acid