Lipocalin-2 Deficiency Reduces Oxidative Stress and Neuroinflammation and Results in Attenuation of Kainic Acid-Induced Hippocampal Cell Death
The hippocampal cell death that follows kainic acid (KA)-induced seizures is associated with blood–brain barrier (BBB) leakage and oxidative stress. Lipocalin-2 (LCN2) is an iron-trafficking protein which contributes to both oxidative stress and inflammation. However, LCN2′s role in KA-induced hippo...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-01-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/10/1/100 |
| _version_ | 1797412537286787072 |
|---|---|
| author | Hyun Joo Shin Eun Ae Jeong Jong Youl Lee Hyeong Seok An Hye Min Jang Yu Jeong Ahn Jaewoong Lee Kyung Eun Kim Gu Seob Roh |
| author_facet | Hyun Joo Shin Eun Ae Jeong Jong Youl Lee Hyeong Seok An Hye Min Jang Yu Jeong Ahn Jaewoong Lee Kyung Eun Kim Gu Seob Roh |
| author_sort | Hyun Joo Shin |
| collection | DOAJ |
| description | The hippocampal cell death that follows kainic acid (KA)-induced seizures is associated with blood–brain barrier (BBB) leakage and oxidative stress. Lipocalin-2 (LCN2) is an iron-trafficking protein which contributes to both oxidative stress and inflammation. However, LCN2′s role in KA-induced hippocampal cell death is not clear. Here, we examine the effect of blocking LCN2 genetically on neuroinflammation and oxidative stress in KA-induced neuronal death. LCN2 deficiency reduced neuronal cell death and BBB leakage in the KA-treated hippocampus. In addition to LCN2 upregulation in the KA-treated hippocampus, circulating LCN2 levels were significantly increased in KA-treated wild-type (WT) mice. In LCN2 knockout mice, we found that the expressions of neutrophil markers myeloperoxidase and neutrophil elastase were decreased compared to their expressions in WT mice following KA treatment. Furthermore, LCN2 deficiency also attenuated KA-induced iron overload and oxidative stress in the hippocampus. These findings indicate that LCN2 may play an important role in iron-related oxidative stress and neuroinflammation in KA-induced hippocampal cell death. |
| first_indexed | 2024-03-09T05:04:25Z |
| format | Article |
| id | doaj.art-cb8ee742aabd4176a6f391625ff72620 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T05:04:25Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-cb8ee742aabd4176a6f391625ff726202023-12-03T12:56:50ZengMDPI AGAntioxidants2076-39212021-01-0110110010.3390/antiox10010100Lipocalin-2 Deficiency Reduces Oxidative Stress and Neuroinflammation and Results in Attenuation of Kainic Acid-Induced Hippocampal Cell DeathHyun Joo Shin0Eun Ae Jeong1Jong Youl Lee2Hyeong Seok An3Hye Min Jang4Yu Jeong Ahn5Jaewoong Lee6Kyung Eun Kim7Gu Seob Roh8Department of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaThe hippocampal cell death that follows kainic acid (KA)-induced seizures is associated with blood–brain barrier (BBB) leakage and oxidative stress. Lipocalin-2 (LCN2) is an iron-trafficking protein which contributes to both oxidative stress and inflammation. However, LCN2′s role in KA-induced hippocampal cell death is not clear. Here, we examine the effect of blocking LCN2 genetically on neuroinflammation and oxidative stress in KA-induced neuronal death. LCN2 deficiency reduced neuronal cell death and BBB leakage in the KA-treated hippocampus. In addition to LCN2 upregulation in the KA-treated hippocampus, circulating LCN2 levels were significantly increased in KA-treated wild-type (WT) mice. In LCN2 knockout mice, we found that the expressions of neutrophil markers myeloperoxidase and neutrophil elastase were decreased compared to their expressions in WT mice following KA treatment. Furthermore, LCN2 deficiency also attenuated KA-induced iron overload and oxidative stress in the hippocampus. These findings indicate that LCN2 may play an important role in iron-related oxidative stress and neuroinflammation in KA-induced hippocampal cell death.https://www.mdpi.com/2076-3921/10/1/100kainic acidlipocalin-2oxidative stressneuroinflammationhippocampus |
| spellingShingle | Hyun Joo Shin Eun Ae Jeong Jong Youl Lee Hyeong Seok An Hye Min Jang Yu Jeong Ahn Jaewoong Lee Kyung Eun Kim Gu Seob Roh Lipocalin-2 Deficiency Reduces Oxidative Stress and Neuroinflammation and Results in Attenuation of Kainic Acid-Induced Hippocampal Cell Death Antioxidants kainic acid lipocalin-2 oxidative stress neuroinflammation hippocampus |
| title | Lipocalin-2 Deficiency Reduces Oxidative Stress and Neuroinflammation and Results in Attenuation of Kainic Acid-Induced Hippocampal Cell Death |
| title_full | Lipocalin-2 Deficiency Reduces Oxidative Stress and Neuroinflammation and Results in Attenuation of Kainic Acid-Induced Hippocampal Cell Death |
| title_fullStr | Lipocalin-2 Deficiency Reduces Oxidative Stress and Neuroinflammation and Results in Attenuation of Kainic Acid-Induced Hippocampal Cell Death |
| title_full_unstemmed | Lipocalin-2 Deficiency Reduces Oxidative Stress and Neuroinflammation and Results in Attenuation of Kainic Acid-Induced Hippocampal Cell Death |
| title_short | Lipocalin-2 Deficiency Reduces Oxidative Stress and Neuroinflammation and Results in Attenuation of Kainic Acid-Induced Hippocampal Cell Death |
| title_sort | lipocalin 2 deficiency reduces oxidative stress and neuroinflammation and results in attenuation of kainic acid induced hippocampal cell death |
| topic | kainic acid lipocalin-2 oxidative stress neuroinflammation hippocampus |
| url | https://www.mdpi.com/2076-3921/10/1/100 |
| work_keys_str_mv | AT hyunjooshin lipocalin2deficiencyreducesoxidativestressandneuroinflammationandresultsinattenuationofkainicacidinducedhippocampalcelldeath AT eunaejeong lipocalin2deficiencyreducesoxidativestressandneuroinflammationandresultsinattenuationofkainicacidinducedhippocampalcelldeath AT jongyoullee lipocalin2deficiencyreducesoxidativestressandneuroinflammationandresultsinattenuationofkainicacidinducedhippocampalcelldeath AT hyeongseokan lipocalin2deficiencyreducesoxidativestressandneuroinflammationandresultsinattenuationofkainicacidinducedhippocampalcelldeath AT hyeminjang lipocalin2deficiencyreducesoxidativestressandneuroinflammationandresultsinattenuationofkainicacidinducedhippocampalcelldeath AT yujeongahn lipocalin2deficiencyreducesoxidativestressandneuroinflammationandresultsinattenuationofkainicacidinducedhippocampalcelldeath AT jaewoonglee lipocalin2deficiencyreducesoxidativestressandneuroinflammationandresultsinattenuationofkainicacidinducedhippocampalcelldeath AT kyungeunkim lipocalin2deficiencyreducesoxidativestressandneuroinflammationandresultsinattenuationofkainicacidinducedhippocampalcelldeath AT guseobroh lipocalin2deficiencyreducesoxidativestressandneuroinflammationandresultsinattenuationofkainicacidinducedhippocampalcelldeath |