Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus
Microgravity (modeled by head-tilt bedrest and hind-limb unloading), experienced during prolonged spaceflight, results in neurological consequences, central nervous system (CNS) dysfunction, and potentially impairment during the performance of critical tasks. Similar pathologies are observed in bedr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/11/1838 |
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| author | Linda Rubinstein Frederico Kiffer Stephanie Puukila Moniece G. Lowe Brie Goo Amalia Luthens Ann-Sofie Schreurs Samantha M. Torres Sonette Steczina Candice G. T. Tahimic Antiño R. Allen |
| author_facet | Linda Rubinstein Frederico Kiffer Stephanie Puukila Moniece G. Lowe Brie Goo Amalia Luthens Ann-Sofie Schreurs Samantha M. Torres Sonette Steczina Candice G. T. Tahimic Antiño R. Allen |
| author_sort | Linda Rubinstein |
| collection | DOAJ |
| description | Microgravity (modeled by head-tilt bedrest and hind-limb unloading), experienced during prolonged spaceflight, results in neurological consequences, central nervous system (CNS) dysfunction, and potentially impairment during the performance of critical tasks. Similar pathologies are observed in bedrest, sedentary lifestyle, and muscle disuse on Earth. In our previous study, we saw that head-tilt bedrest together with social isolation upregulated the milieu of pro-inflammatory cytokines in the hippocampus and plasma. These changes were mitigated in a MCAT mouse model overexpressing human catalase in the mitochondria, pointing out the importance of ROS signaling in this stress response. Here, we used a head-tilt model in socially housed mice to tease out the effects of head-tilt bedrest without isolation. In order to find the underlying molecular mechanisms that provoked the cytokine response, we measured CD68, an indicator of microglial activation in the hippocampus, as well as changes in normal in-cage behavior. We hypothesized that hindlimb unloading (HU) will elicit microglial hippocampal activations, which will be mitigated in the MCAT ROS-quenching mice model. Indeed, we saw an elevation of the activated microglia CD68 marker following HU in the hippocampus, and this pathology was mitigated in MCAT mice. Additionally, we identified cytokines in the hippocampus, which had significant positive correlations with CD68 and negative correlations with exploratory behaviors, indicating a link between neuroinflammation and behavioral consequences. Unveiling a correlation between molecular and behavioral changes could reveal a biomarker indicative of these responses and could also result in a potential target for the treatment and prevention of cognitive changes following long space missions and/or muscle disuse on Earth. |
| first_indexed | 2024-03-09T18:55:00Z |
| format | Article |
| id | doaj.art-a238ffcabf174beaa0b5206b859522b7 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T18:55:00Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-a238ffcabf174beaa0b5206b859522b72023-11-24T05:31:45ZengMDPI AGLife2075-17292022-11-011211183810.3390/life12111838Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the HippocampusLinda Rubinstein0Frederico Kiffer1Stephanie Puukila2Moniece G. Lowe3Brie Goo4Amalia Luthens5Ann-Sofie Schreurs6Samantha M. Torres7Sonette Steczina8Candice G. T. Tahimic9Antiño R. Allen10Universities Space Research Association USRA, Columbia, MD 21046, USAChildren’s Hospital of Philadelphia, Philadelphia, PA 19104, USAUniversities Space Research Association USRA, Columbia, MD 21046, USASpace Biosciences Division, NASA Ames Research Center, Moffett Field, Mountain View, CA 94035, USASpace Biosciences Division, NASA Ames Research Center, Moffett Field, Mountain View, CA 94035, USAKBR, Houston, TX 77002, USASpace Biosciences Division, NASA Ames Research Center, Moffett Field, Mountain View, CA 94035, USASpace Biosciences Division, NASA Ames Research Center, Moffett Field, Mountain View, CA 94035, USASpace Biosciences Division, NASA Ames Research Center, Moffett Field, Mountain View, CA 94035, USASpace Biosciences Division, NASA Ames Research Center, Moffett Field, Mountain View, CA 94035, USAChildren’s Hospital of Philadelphia, Philadelphia, PA 19104, USAMicrogravity (modeled by head-tilt bedrest and hind-limb unloading), experienced during prolonged spaceflight, results in neurological consequences, central nervous system (CNS) dysfunction, and potentially impairment during the performance of critical tasks. Similar pathologies are observed in bedrest, sedentary lifestyle, and muscle disuse on Earth. In our previous study, we saw that head-tilt bedrest together with social isolation upregulated the milieu of pro-inflammatory cytokines in the hippocampus and plasma. These changes were mitigated in a MCAT mouse model overexpressing human catalase in the mitochondria, pointing out the importance of ROS signaling in this stress response. Here, we used a head-tilt model in socially housed mice to tease out the effects of head-tilt bedrest without isolation. In order to find the underlying molecular mechanisms that provoked the cytokine response, we measured CD68, an indicator of microglial activation in the hippocampus, as well as changes in normal in-cage behavior. We hypothesized that hindlimb unloading (HU) will elicit microglial hippocampal activations, which will be mitigated in the MCAT ROS-quenching mice model. Indeed, we saw an elevation of the activated microglia CD68 marker following HU in the hippocampus, and this pathology was mitigated in MCAT mice. Additionally, we identified cytokines in the hippocampus, which had significant positive correlations with CD68 and negative correlations with exploratory behaviors, indicating a link between neuroinflammation and behavioral consequences. Unveiling a correlation between molecular and behavioral changes could reveal a biomarker indicative of these responses and could also result in a potential target for the treatment and prevention of cognitive changes following long space missions and/or muscle disuse on Earth.https://www.mdpi.com/2075-1729/12/11/1838microgravityCNShind limb unloadingmicrogliaROSMCAT |
| spellingShingle | Linda Rubinstein Frederico Kiffer Stephanie Puukila Moniece G. Lowe Brie Goo Amalia Luthens Ann-Sofie Schreurs Samantha M. Torres Sonette Steczina Candice G. T. Tahimic Antiño R. Allen Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus Life microgravity CNS hind limb unloading microglia ROS MCAT |
| title | Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus |
| title_full | Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus |
| title_fullStr | Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus |
| title_full_unstemmed | Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus |
| title_short | Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus |
| title_sort | mitochondria targeted human catalase in the mouse longevity mcat model mitigates head tilt bedrest induced neuro inflammation in the hippocampus |
| topic | microgravity CNS hind limb unloading microglia ROS MCAT |
| url | https://www.mdpi.com/2075-1729/12/11/1838 |
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