Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress
Reelin, an extracellular matrix protein with putative antidepressant-like properties, becomes dysregulated by chronic stress. Improvement in cognitive dysfunction and depression-like behavior induced by chronic stress has been reported with both intrahippocampal and intravenous Reelin treatment but...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2023-03-01
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| Series: | Chronic Stress |
| Online Access: | https://doi.org/10.1177/24705470231164920 |
| _version_ | 1797845697365540864 |
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| author | B.S. Reive Jenessa N. Johnston Carla L. Sánchez-Lafuente Lucy Zhang Aland Chang Jasmine Zhang Josh Allen Raquel Romay-Tallon Lisa E. Kalynchuk Hector J. Caruncho |
| author_facet | B.S. Reive Jenessa N. Johnston Carla L. Sánchez-Lafuente Lucy Zhang Aland Chang Jasmine Zhang Josh Allen Raquel Romay-Tallon Lisa E. Kalynchuk Hector J. Caruncho |
| author_sort | B.S. Reive |
| collection | DOAJ |
| description | Reelin, an extracellular matrix protein with putative antidepressant-like properties, becomes dysregulated by chronic stress. Improvement in cognitive dysfunction and depression-like behavior induced by chronic stress has been reported with both intrahippocampal and intravenous Reelin treatment but the mechanisms responsible are not clear. To determine if treatment with Reelin modifies chronic stress-induced dysfunction in immune organs and whether this relates to behavioral and/or neurochemical outcomes, spleens were collected from both male (n = 62) and female (n = 53) rats treated with daily corticosterone injections for three weeks that received Reelin or vehicle. Reelin was intravenously administered once on the final day of chronic stress, or repeatedly, with weekly treatments throughout chronic stress. Behavior was assessed during the forced swim test and the object-in-place test. Chronic corticosterone caused significant atrophy of the spleen white pulp, but treatment with a single shot of Reelin restored white pulp in both males and females. Repeated Reelin injections also resolved atrophy in females. Correlations were observed between recovery of white pulp atrophy and recovery of behavioral deficits and expression of both Reelin and glutamate receptor 1 in the hippocampus, supporting a role of the peripheral immune system in the recovery of chronic stress-induced behaviors following treatment with Reelin. Our data adds to research indicating Reelin could be a valuable therapeutic target for chronic stress-related disorders including major depression. |
| first_indexed | 2024-04-09T17:43:12Z |
| format | Article |
| id | doaj.art-ce231d6724ee44a1a19e8e73a36f702b |
| institution | Directory Open Access Journal |
| issn | 2470-5470 |
| language | English |
| last_indexed | 2024-04-09T17:43:12Z |
| publishDate | 2023-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Chronic Stress |
| spelling | doaj.art-ce231d6724ee44a1a19e8e73a36f702b2023-04-17T03:03:19ZengSAGE PublishingChronic Stress2470-54702023-03-01710.1177/24705470231164920Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic StressB.S. Reive0Jenessa N. Johnston1Carla L. Sánchez-Lafuente2Lucy Zhang3Aland Chang4Jasmine Zhang5Josh Allen6Raquel Romay-Tallon7Lisa E. Kalynchuk8Hector J. Caruncho9 Division of Medical Sciences, , Victoria, Canada Division of Medical Sciences, , Victoria, Canada Division of Medical Sciences, , Victoria, Canada , Victoria, Canada , Victoria, Canada , Victoria, Canada Division of Medical Sciences, , Victoria, Canada Department of Psychiatry, University of Illinois at Chicago, Chicago, USA Division of Medical Sciences, , Victoria, Canada Division of Medical Sciences, , Victoria, CanadaReelin, an extracellular matrix protein with putative antidepressant-like properties, becomes dysregulated by chronic stress. Improvement in cognitive dysfunction and depression-like behavior induced by chronic stress has been reported with both intrahippocampal and intravenous Reelin treatment but the mechanisms responsible are not clear. To determine if treatment with Reelin modifies chronic stress-induced dysfunction in immune organs and whether this relates to behavioral and/or neurochemical outcomes, spleens were collected from both male (n = 62) and female (n = 53) rats treated with daily corticosterone injections for three weeks that received Reelin or vehicle. Reelin was intravenously administered once on the final day of chronic stress, or repeatedly, with weekly treatments throughout chronic stress. Behavior was assessed during the forced swim test and the object-in-place test. Chronic corticosterone caused significant atrophy of the spleen white pulp, but treatment with a single shot of Reelin restored white pulp in both males and females. Repeated Reelin injections also resolved atrophy in females. Correlations were observed between recovery of white pulp atrophy and recovery of behavioral deficits and expression of both Reelin and glutamate receptor 1 in the hippocampus, supporting a role of the peripheral immune system in the recovery of chronic stress-induced behaviors following treatment with Reelin. Our data adds to research indicating Reelin could be a valuable therapeutic target for chronic stress-related disorders including major depression.https://doi.org/10.1177/24705470231164920 |
| spellingShingle | B.S. Reive Jenessa N. Johnston Carla L. Sánchez-Lafuente Lucy Zhang Aland Chang Jasmine Zhang Josh Allen Raquel Romay-Tallon Lisa E. Kalynchuk Hector J. Caruncho Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress Chronic Stress |
| title | Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress |
| title_full | Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress |
| title_fullStr | Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress |
| title_full_unstemmed | Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress |
| title_short | Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress |
| title_sort | intravenous reelin treatment rescues atrophy of spleen white pulp and correlates to rescue of forced swim test immobility and neurochemical alterations induced by chronic stress |
| url | https://doi.org/10.1177/24705470231164920 |
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