Is the Relationship Between Adolescent Social Isolation and Anxiety‐Like Behaviors Altered by Microglia Ablation in Female Long Evans Rats?
ABSTRACT Objective Despite extensive, cross‐disciplinary research revealing a relationship between early life stress (ELS) and an increased risk for neuropsychiatric disorders, the underlying processes mediating this relationship are not fully understood. Further, the majority of preclinical studies...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-03-01
|
| Series: | Brain and Behavior |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/brb3.70369 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850185010323128320 |
|---|---|
| author | Matthew A. Blumberg Ava Shipman Lidia Olyha Stephen C. Gironda Jeffrey L. Weiner |
| author_facet | Matthew A. Blumberg Ava Shipman Lidia Olyha Stephen C. Gironda Jeffrey L. Weiner |
| author_sort | Matthew A. Blumberg |
| collection | DOAJ |
| description | ABSTRACT Objective Despite extensive, cross‐disciplinary research revealing a relationship between early life stress (ELS) and an increased risk for neuropsychiatric disorders, the underlying processes mediating this relationship are not fully understood. Further, the majority of preclinical studies investigating this relationship have not taken sex differences into consideration. A growing body of work suggests that microglia, resident immune cells of the brain, are impacted by ELS and contribute to some of the maladaptive behavioral phenotypes in adulthood. Here, we utilized an adolescent social isolation (aSI) model of ELS in female rats to test the role of microglia in mediating the effects of ELS on anxiety‐related behaviors. Methods The present study sought to determine whether microglia ablation during aSI could prevent anxiety‐like behaviors in female Long Evans rats. A colony‐stimulating factor 1 receptor (CSF1‐r) inhibitor, PLX3397, was provided in chow to ablate microglia at the start of the isolation period (postnatal day (P) 21–42). During the aSI period, animals performed a battery of behavioral assays including the open field test, elevated plus maze, and successive alleys test. Following completion of the behavioral assays, brain tissue was collected to confirm the efficacy of PLX3397 and identify changes in microglia population density. Results Relative to group‐housed (GH) controls, aSI rats showed increased locomotor activity in the open field test and higher closed‐arm entries on the elevated plus maze. Although PLX3397 effectively ablated microglia across all animals, this treatment had minimal effects on observed aSI‐associated phenotypes. Conclusions Together, these data suggest that microglia are not required for behavioral adaptations promoted by aSI. Future studies will be needed to assess the role of microglia in the relationship between ELS and maladaptive behavioral phenotypes. |
| format | Article |
| id | doaj-art-93df2e9b0c6f4b67a658db554864bac8 |
| institution | OA Journals |
| issn | 2162-3279 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj-art-93df2e9b0c6f4b67a658db554864bac82025-08-20T02:16:54ZengWileyBrain and Behavior2162-32792025-03-01153n/an/a10.1002/brb3.70369Is the Relationship Between Adolescent Social Isolation and Anxiety‐Like Behaviors Altered by Microglia Ablation in Female Long Evans Rats?Matthew A. Blumberg0Ava Shipman1Lidia Olyha2Stephen C. Gironda3Jeffrey L. Weiner4Department of Translational Neuroscience Wake Forest University School of Medicine Winston‐Salem North Carolina USADepartment of Translational Neuroscience Wake Forest University School of Medicine Winston‐Salem North Carolina USADepartment of Translational Neuroscience Wake Forest University School of Medicine Winston‐Salem North Carolina USADepartment of Translational Neuroscience Wake Forest University School of Medicine Winston‐Salem North Carolina USADepartment of Translational Neuroscience Wake Forest University School of Medicine Winston‐Salem North Carolina USAABSTRACT Objective Despite extensive, cross‐disciplinary research revealing a relationship between early life stress (ELS) and an increased risk for neuropsychiatric disorders, the underlying processes mediating this relationship are not fully understood. Further, the majority of preclinical studies investigating this relationship have not taken sex differences into consideration. A growing body of work suggests that microglia, resident immune cells of the brain, are impacted by ELS and contribute to some of the maladaptive behavioral phenotypes in adulthood. Here, we utilized an adolescent social isolation (aSI) model of ELS in female rats to test the role of microglia in mediating the effects of ELS on anxiety‐related behaviors. Methods The present study sought to determine whether microglia ablation during aSI could prevent anxiety‐like behaviors in female Long Evans rats. A colony‐stimulating factor 1 receptor (CSF1‐r) inhibitor, PLX3397, was provided in chow to ablate microglia at the start of the isolation period (postnatal day (P) 21–42). During the aSI period, animals performed a battery of behavioral assays including the open field test, elevated plus maze, and successive alleys test. Following completion of the behavioral assays, brain tissue was collected to confirm the efficacy of PLX3397 and identify changes in microglia population density. Results Relative to group‐housed (GH) controls, aSI rats showed increased locomotor activity in the open field test and higher closed‐arm entries on the elevated plus maze. Although PLX3397 effectively ablated microglia across all animals, this treatment had minimal effects on observed aSI‐associated phenotypes. Conclusions Together, these data suggest that microglia are not required for behavioral adaptations promoted by aSI. Future studies will be needed to assess the role of microglia in the relationship between ELS and maladaptive behavioral phenotypes.https://doi.org/10.1002/brb3.70369anxietymicrogliaPLX3397 (Pexidartinib)social isolation |
| spellingShingle | Matthew A. Blumberg Ava Shipman Lidia Olyha Stephen C. Gironda Jeffrey L. Weiner Is the Relationship Between Adolescent Social Isolation and Anxiety‐Like Behaviors Altered by Microglia Ablation in Female Long Evans Rats? Brain and Behavior anxiety microglia PLX3397 (Pexidartinib) social isolation |
| title | Is the Relationship Between Adolescent Social Isolation and Anxiety‐Like Behaviors Altered by Microglia Ablation in Female Long Evans Rats? |
| title_full | Is the Relationship Between Adolescent Social Isolation and Anxiety‐Like Behaviors Altered by Microglia Ablation in Female Long Evans Rats? |
| title_fullStr | Is the Relationship Between Adolescent Social Isolation and Anxiety‐Like Behaviors Altered by Microglia Ablation in Female Long Evans Rats? |
| title_full_unstemmed | Is the Relationship Between Adolescent Social Isolation and Anxiety‐Like Behaviors Altered by Microglia Ablation in Female Long Evans Rats? |
| title_short | Is the Relationship Between Adolescent Social Isolation and Anxiety‐Like Behaviors Altered by Microglia Ablation in Female Long Evans Rats? |
| title_sort | is the relationship between adolescent social isolation and anxiety like behaviors altered by microglia ablation in female long evans rats |
| topic | anxiety microglia PLX3397 (Pexidartinib) social isolation |
| url | https://doi.org/10.1002/brb3.70369 |
| work_keys_str_mv | AT matthewablumberg istherelationshipbetweenadolescentsocialisolationandanxietylikebehaviorsalteredbymicrogliaablationinfemalelongevansrats AT avashipman istherelationshipbetweenadolescentsocialisolationandanxietylikebehaviorsalteredbymicrogliaablationinfemalelongevansrats AT lidiaolyha istherelationshipbetweenadolescentsocialisolationandanxietylikebehaviorsalteredbymicrogliaablationinfemalelongevansrats AT stephencgironda istherelationshipbetweenadolescentsocialisolationandanxietylikebehaviorsalteredbymicrogliaablationinfemalelongevansrats AT jeffreylweiner istherelationshipbetweenadolescentsocialisolationandanxietylikebehaviorsalteredbymicrogliaablationinfemalelongevansrats |