The significant increase in astrocytic density and astrocyte activation observed in the hippocampus of rats consuming morphine for fifty-six days was reduced by the administration of NAC, ibudilast, and the combined administration of both drugs (NAC + ibudilast).
<p><b>(A)</b> Representative confocal microphotographs of GFAP immunoreactivity (green top) in hippocampal astrocytes. Nuclei were counterstained with DAPI (blue, nuclear marker), scale bar 25 μm. <b>(B)</b> Quantification of astrocyte density and <b>(C)</b>...
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2024
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| _version_ | 1852025582693384192 |
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| author | María Elena Quintanilla (8068691) |
| author2 | Paola Morales (19967) Daniela Santapau (317108) Javiera Gallardo (19964414) Rocío Rebolledo (19964417) Gabriel Riveras (19964420) Tirso Acuña (19964423) Mario Herrera-Marschitz (19968) Yedy Israel (6932069) Fernando Ezquer (356930) |
| author2_role | author author author author author author author author author |
| author_facet | María Elena Quintanilla (8068691) Paola Morales (19967) Daniela Santapau (317108) Javiera Gallardo (19964414) Rocío Rebolledo (19964417) Gabriel Riveras (19964420) Tirso Acuña (19964423) Mario Herrera-Marschitz (19968) Yedy Israel (6932069) Fernando Ezquer (356930) |
| author_role | author |
| dc.creator.none.fl_str_mv | María Elena Quintanilla (8068691) Paola Morales (19967) Daniela Santapau (317108) Javiera Gallardo (19964414) Rocío Rebolledo (19964417) Gabriel Riveras (19964420) Tirso Acuña (19964423) Mario Herrera-Marschitz (19968) Yedy Israel (6932069) Fernando Ezquer (356930) |
| dc.date.none.fl_str_mv | 2024-10-29T17:33:36Z |
| dc.identifier.none.fl_str_mv | 10.1371/journal.pone.0312828.g004 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/The_significant_increase_in_astrocytic_density_and_astrocyte_activation_observed_in_the_hippocampus_of_rats_consuming_morphine_for_fifty-six_days_was_reduced_by_the_administration_of_NAC_ibudilast_and_the_combined_administration_of_both_dru/27326717 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biochemistry Cell Biology Molecular Biology Neuroscience Pharmacology Cancer Mental Health Infectious Diseases opioid use disorders illicit opioid procurement glutamate transporters glt glutamate transporter glt derived uchb rats compelling evidence indicating voluntary morphine intake chronic morphine intake perpetuates drug intake gradually reducing dependence voluntary morphine self xlink "> separate therapeutic agents resulted present study aimed oxidative stress induced ibudilast markedly reduced associated glial activation administration </ p morphine self xlink "> oxidative stress drug recall dependence would translational value region involved nucleus accumbens mild reduction medical administration lower level joint administration inflammatory ibudilast ibudilast led glutamatergic homeostasis extended period effect enhanced continued maintenance combined administration animal model administered either 5 mg 40 mg |
| dc.title.none.fl_str_mv | The significant increase in astrocytic density and astrocyte activation observed in the hippocampus of rats consuming morphine for fifty-six days was reduced by the administration of NAC, ibudilast, and the combined administration of both drugs (NAC + ibudilast). |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | <p><b>(A)</b> Representative confocal microphotographs of GFAP immunoreactivity (green top) in hippocampal astrocytes. Nuclei were counterstained with DAPI (blue, nuclear marker), scale bar 25 μm. <b>(B)</b> Quantification of astrocyte density and <b>(C)</b> Length of primary astrocytic processes showing individual values. The inset displays a representative hippocampal microphotograph, indicating the area analyzed in <i>stratum radiatum (sr)</i> from CA1 region, depicted by white boxes. Shapiro-Wilk tests performed on data from either the groups of astrocytic length data (A) or the groups of astrocytic density data (B) indicate that only astrocytic density datasets met the criteria for normality (alpha = 0.05), while astrocytic length data did not pass normality tests, implying that data for the astrocytic density follow a normal distribution and length size of astrocytic processes data do not exhibit a normal/Gaussian distribution, thereby they were analyzed using the non-parametric Kruskal-Wallis test. (A) Kruskal-Wallis analysis of all astrocytic length data indicates a significant difference between groups (Kruskal-Wallis statistic: 181.7, ****p<0.0001). Dunn´s post-hoc test indicate that the morphine drinking group exhibits a higher length size of astrocytic process compared to water drinking rats (****p<0.0001). The administration of NAC (***p<0.0001), ibudilast (****p<0.0001) and NAC + ibudilast (****p<0.0001) fully normalized the morphine-induced increases in the length size of astrocytic process compared to the morphine drinking group treated with vehicle. (B) One-way ANOVA followed by Tukey’s post-hoc test revealed that chronic morphine intake (56 days) by rats treated with vehicle (morphine + vehicle) led to an increase in astrocytic density [<i>F</i><sub>treatment(4,274)</sub> = 26.0, ****p<0.0001], and length of astrocytic processes. At the administered doses, ibudilast, but not NAC, reduced the chronic morphine-induced increase in astrocytic density (****p<0.0001). This inhibition was synergistically increased by the co-administration of NAC + ibudilast when compared with either the NAC (***p<0.001) or ibudilast (**p<0.01) groups.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_ffda2ebf555ba1f68112768aef26be21 |
| identifier_str_mv | 10.1371/journal.pone.0312828.g004 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/27326717 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | The significant increase in astrocytic density and astrocyte activation observed in the hippocampus of rats consuming morphine for fifty-six days was reduced by the administration of NAC, ibudilast, and the combined administration of both drugs (NAC + ibudilast).María Elena Quintanilla (8068691)Paola Morales (19967)Daniela Santapau (317108)Javiera Gallardo (19964414)Rocío Rebolledo (19964417)Gabriel Riveras (19964420)Tirso Acuña (19964423)Mario Herrera-Marschitz (19968)Yedy Israel (6932069)Fernando Ezquer (356930)BiochemistryCell BiologyMolecular BiologyNeurosciencePharmacologyCancerMental HealthInfectious Diseasesopioid use disordersillicit opioid procurementglutamate transporters gltglutamate transporter gltderived uchb ratscompelling evidence indicatingvoluntary morphine intakechronic morphine intakeperpetuates drug intakegradually reducing dependencevoluntary morphine selfxlink "> separatetherapeutic agents resultedpresent study aimedoxidative stress inducedibudilast markedly reducedassociated glial activationadministration </ pmorphine selfxlink ">oxidative stressdrug recalldependence wouldtranslational valueregion involvednucleus accumbensmild reductionmedical administrationlower leveljoint administrationinflammatory ibudilastibudilast ledglutamatergic homeostasisextended periodeffect enhancedcontinued maintenancecombined administrationanimal modeladministered either5 mg40 mg<p><b>(A)</b> Representative confocal microphotographs of GFAP immunoreactivity (green top) in hippocampal astrocytes. Nuclei were counterstained with DAPI (blue, nuclear marker), scale bar 25 μm. <b>(B)</b> Quantification of astrocyte density and <b>(C)</b> Length of primary astrocytic processes showing individual values. The inset displays a representative hippocampal microphotograph, indicating the area analyzed in <i>stratum radiatum (sr)</i> from CA1 region, depicted by white boxes. Shapiro-Wilk tests performed on data from either the groups of astrocytic length data (A) or the groups of astrocytic density data (B) indicate that only astrocytic density datasets met the criteria for normality (alpha = 0.05), while astrocytic length data did not pass normality tests, implying that data for the astrocytic density follow a normal distribution and length size of astrocytic processes data do not exhibit a normal/Gaussian distribution, thereby they were analyzed using the non-parametric Kruskal-Wallis test. (A) Kruskal-Wallis analysis of all astrocytic length data indicates a significant difference between groups (Kruskal-Wallis statistic: 181.7, ****p<0.0001). Dunn´s post-hoc test indicate that the morphine drinking group exhibits a higher length size of astrocytic process compared to water drinking rats (****p<0.0001). The administration of NAC (***p<0.0001), ibudilast (****p<0.0001) and NAC + ibudilast (****p<0.0001) fully normalized the morphine-induced increases in the length size of astrocytic process compared to the morphine drinking group treated with vehicle. (B) One-way ANOVA followed by Tukey’s post-hoc test revealed that chronic morphine intake (56 days) by rats treated with vehicle (morphine + vehicle) led to an increase in astrocytic density [<i>F</i><sub>treatment(4,274)</sub> = 26.0, ****p<0.0001], and length of astrocytic processes. At the administered doses, ibudilast, but not NAC, reduced the chronic morphine-induced increase in astrocytic density (****p<0.0001). This inhibition was synergistically increased by the co-administration of NAC + ibudilast when compared with either the NAC (***p<0.001) or ibudilast (**p<0.01) groups.</p>2024-10-29T17:33:36ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.1371/journal.pone.0312828.g004https://figshare.com/articles/figure/The_significant_increase_in_astrocytic_density_and_astrocyte_activation_observed_in_the_hippocampus_of_rats_consuming_morphine_for_fifty-six_days_was_reduced_by_the_administration_of_NAC_ibudilast_and_the_combined_administration_of_both_dru/27326717CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/273267172024-10-29T17:33:36Z |
| spellingShingle | The significant increase in astrocytic density and astrocyte activation observed in the hippocampus of rats consuming morphine for fifty-six days was reduced by the administration of NAC, ibudilast, and the combined administration of both drugs (NAC + ibudilast). María Elena Quintanilla (8068691) Biochemistry Cell Biology Molecular Biology Neuroscience Pharmacology Cancer Mental Health Infectious Diseases opioid use disorders illicit opioid procurement glutamate transporters glt glutamate transporter glt derived uchb rats compelling evidence indicating voluntary morphine intake chronic morphine intake perpetuates drug intake gradually reducing dependence voluntary morphine self xlink "> separate therapeutic agents resulted present study aimed oxidative stress induced ibudilast markedly reduced associated glial activation administration </ p morphine self xlink "> oxidative stress drug recall dependence would translational value region involved nucleus accumbens mild reduction medical administration lower level joint administration inflammatory ibudilast ibudilast led glutamatergic homeostasis extended period effect enhanced continued maintenance combined administration animal model administered either 5 mg 40 mg |
| status_str | publishedVersion |
| title | The significant increase in astrocytic density and astrocyte activation observed in the hippocampus of rats consuming morphine for fifty-six days was reduced by the administration of NAC, ibudilast, and the combined administration of both drugs (NAC + ibudilast). |
| title_full | The significant increase in astrocytic density and astrocyte activation observed in the hippocampus of rats consuming morphine for fifty-six days was reduced by the administration of NAC, ibudilast, and the combined administration of both drugs (NAC + ibudilast). |
| title_fullStr | The significant increase in astrocytic density and astrocyte activation observed in the hippocampus of rats consuming morphine for fifty-six days was reduced by the administration of NAC, ibudilast, and the combined administration of both drugs (NAC + ibudilast). |
| title_full_unstemmed | The significant increase in astrocytic density and astrocyte activation observed in the hippocampus of rats consuming morphine for fifty-six days was reduced by the administration of NAC, ibudilast, and the combined administration of both drugs (NAC + ibudilast). |
| title_short | The significant increase in astrocytic density and astrocyte activation observed in the hippocampus of rats consuming morphine for fifty-six days was reduced by the administration of NAC, ibudilast, and the combined administration of both drugs (NAC + ibudilast). |
| title_sort | The significant increase in astrocytic density and astrocyte activation observed in the hippocampus of rats consuming morphine for fifty-six days was reduced by the administration of NAC, ibudilast, and the combined administration of both drugs (NAC + ibudilast). |
| topic | Biochemistry Cell Biology Molecular Biology Neuroscience Pharmacology Cancer Mental Health Infectious Diseases opioid use disorders illicit opioid procurement glutamate transporters glt glutamate transporter glt derived uchb rats compelling evidence indicating voluntary morphine intake chronic morphine intake perpetuates drug intake gradually reducing dependence voluntary morphine self xlink "> separate therapeutic agents resulted present study aimed oxidative stress induced ibudilast markedly reduced associated glial activation administration </ p morphine self xlink "> oxidative stress drug recall dependence would translational value region involved nucleus accumbens mild reduction medical administration lower level joint administration inflammatory ibudilast ibudilast led glutamatergic homeostasis extended period effect enhanced continued maintenance combined administration animal model administered either 5 mg 40 mg |