Altered Hippocampal and Striatal Expression of Endothelial Markers and VIP/PACAP Neuropeptides in a Mouse Model of Systemic Lupus Erythematosus
Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most common and severe manifestations of lupus; however, its pathogenesis is still poorly understood. While there is sparse evidence suggesting that the ongoing autoimmunity may trigger pathogenic changes to the central nervous syst...
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| Veröffentlicht in: | International journal of molecular sciences 2023-07, Vol.24 (13), p.11118 |
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| description | Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most common and severe manifestations of lupus; however, its pathogenesis is still poorly understood. While there is sparse evidence suggesting that the ongoing autoimmunity may trigger pathogenic changes to the central nervous system (CNS) microvasculature, culminating in inflammatory/ischemic damage, further evidence is still needed. In this study, we used the spontaneous mouse model of SLE (NZBWF1 mice) to investigate the expression of genes and proteins associated with endothelial (dys)function: tissue and urokinase plasminogen activators (tPA and uPA), intercellular and vascular adhesion molecules 1 (ICAM-1 and VCAM-1), brain derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 4 (KLF4) and neuroprotection/immune modulation: pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), PACAP receptor (PAC1), VIP receptors 1 and 2 (VPAC1 and VPAC2). Analyses were carried out both in the hippocampus and striatum of SLE mice of two different age groups (2 and 7 months old), since age correlates with disease severity. In the hippocampus, we identified a gene/protein expression profile indicative of mild endothelial dysfunction, which increased in severity in aged SLE mice. These alterations were paralleled by moderate alterations in the expression of VIP, PACAP and related receptors. In contrast, we report a robust upregulation of endothelial activation markers in the striatum of both young and aged mice, concurrent with significant induction of the VIP/PACAP system. These data identify molecular signatures of endothelial alterations in the hippocampus and striatum of NZBWF1 mice, which are accompanied by a heightened expression of endogenous protective/immune-modulatory neuropeptides. Collectively, our results support the idea that NPSLE may cause alterations of the CNS micro-vascular compartment that cannot be effectively counteracted by the endogenous activity of the neuropeptides PACAP and VIP. |
| doi_str_mv | 10.3390/ijms241311118 |
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While there is sparse evidence suggesting that the ongoing autoimmunity may trigger pathogenic changes to the central nervous system (CNS) microvasculature, culminating in inflammatory/ischemic damage, further evidence is still needed. In this study, we used the spontaneous mouse model of SLE (NZBWF1 mice) to investigate the expression of genes and proteins associated with endothelial (dys)function: tissue and urokinase plasminogen activators (tPA and uPA), intercellular and vascular adhesion molecules 1 (ICAM-1 and VCAM-1), brain derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 4 (KLF4) and neuroprotection/immune modulation: pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), PACAP receptor (PAC1), VIP receptors 1 and 2 (VPAC1 and VPAC2). Analyses were carried out both in the hippocampus and striatum of SLE mice of two different age groups (2 and 7 months old), since age correlates with disease severity. In the hippocampus, we identified a gene/protein expression profile indicative of mild endothelial dysfunction, which increased in severity in aged SLE mice. These alterations were paralleled by moderate alterations in the expression of VIP, PACAP and related receptors. In contrast, we report a robust upregulation of endothelial activation markers in the striatum of both young and aged mice, concurrent with significant induction of the VIP/PACAP system. These data identify molecular signatures of endothelial alterations in the hippocampus and striatum of NZBWF1 mice, which are accompanied by a heightened expression of endogenous protective/immune-modulatory neuropeptides. Collectively, our results support the idea that NPSLE may cause alterations of the CNS micro-vascular compartment that cannot be effectively counteracted by the endogenous activity of the neuropeptides PACAP and VIP.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms241311118</identifier><identifier>PMID: 37446298</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Age groups ; Animals ; Autoimmunity ; Brain-derived neurotrophic factor ; Central nervous system ; Chronic conditions ; Endothelium ; Enzymes ; Gene expression ; Genetic aspects ; Hippocampus ; Immunomodulation ; Inflammation ; Intercellular adhesion molecule 1 ; Ischemia ; KLF4 protein ; Krueppel-like factor ; Lupus ; Lupus Erythematosus, Systemic ; Mice ; Microvasculature ; Neostriatum ; Neurological complications ; Neuromodulation ; Neuropeptides ; Neuroprotection ; Nitric oxide ; Nitric-oxide synthase ; PAC1 protein ; Peptides ; Pituitary adenylate cyclase-activating polypeptide ; Pituitary Adenylate Cyclase-Activating Polypeptide - metabolism ; Protein expression ; Proteins ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I - metabolism ; Receptors, Vasoactive Intestinal Peptide, Type II ; Receptors, Vasoactive Intestinal Polypeptide, Type I ; Systemic lupus erythematosus ; t-Plasminogen activator ; Tissue plasminogen activator ; Transcription factors ; U-Plasminogen activator ; Urokinase ; Vascular cell adhesion molecule 1 ; Vasoactive agents ; Vasoactive Intestinal Peptide - metabolism ; Vasoactive intestinal peptides</subject><ispartof>International journal of molecular sciences, 2023-07, Vol.24 (13), p.11118</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c439t-c8f61999471b4fb2b403e3aac24079638bfb2b2b458d03461ba7335ccadb3e0c3</cites><orcidid>0000-0002-5444-0920 ; 0000-0002-4165-4276 ; 0000-0002-8260-8890 ; 0000-0001-7037-759X ; 0000-0003-0721-4055 ; 0009-0000-5583-0579 ; 0000-0001-9365-342X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342033/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342033/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37446298$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Jayden</creatorcontrib><creatorcontrib>Thomas Broome, Sarah</creatorcontrib><creatorcontrib>Jansen, Margo Iris</creatorcontrib><creatorcontrib>Mandwie, Mawj</creatorcontrib><creatorcontrib>Logan, Grant J</creatorcontrib><creatorcontrib>Marzagalli, Rubina</creatorcontrib><creatorcontrib>Musumeci, Giuseppe</creatorcontrib><creatorcontrib>Castorina, Alessandro</creatorcontrib><title>Altered Hippocampal and Striatal Expression of Endothelial Markers and VIP/PACAP Neuropeptides in a Mouse Model of Systemic Lupus Erythematosus</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most common and severe manifestations of lupus; however, its pathogenesis is still poorly understood. While there is sparse evidence suggesting that the ongoing autoimmunity may trigger pathogenic changes to the central nervous system (CNS) microvasculature, culminating in inflammatory/ischemic damage, further evidence is still needed. In this study, we used the spontaneous mouse model of SLE (NZBWF1 mice) to investigate the expression of genes and proteins associated with endothelial (dys)function: tissue and urokinase plasminogen activators (tPA and uPA), intercellular and vascular adhesion molecules 1 (ICAM-1 and VCAM-1), brain derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 4 (KLF4) and neuroprotection/immune modulation: pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), PACAP receptor (PAC1), VIP receptors 1 and 2 (VPAC1 and VPAC2). Analyses were carried out both in the hippocampus and striatum of SLE mice of two different age groups (2 and 7 months old), since age correlates with disease severity. In the hippocampus, we identified a gene/protein expression profile indicative of mild endothelial dysfunction, which increased in severity in aged SLE mice. These alterations were paralleled by moderate alterations in the expression of VIP, PACAP and related receptors. In contrast, we report a robust upregulation of endothelial activation markers in the striatum of both young and aged mice, concurrent with significant induction of the VIP/PACAP system. These data identify molecular signatures of endothelial alterations in the hippocampus and striatum of NZBWF1 mice, which are accompanied by a heightened expression of endogenous protective/immune-modulatory neuropeptides. Collectively, our results support the idea that NPSLE may cause alterations of the CNS micro-vascular compartment that cannot be effectively counteracted by the endogenous activity of the neuropeptides PACAP and VIP.</description><subject>Age groups</subject><subject>Animals</subject><subject>Autoimmunity</subject><subject>Brain-derived neurotrophic factor</subject><subject>Central nervous system</subject><subject>Chronic conditions</subject><subject>Endothelium</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Hippocampus</subject><subject>Immunomodulation</subject><subject>Inflammation</subject><subject>Intercellular adhesion molecule 1</subject><subject>Ischemia</subject><subject>KLF4 protein</subject><subject>Krueppel-like factor</subject><subject>Lupus</subject><subject>Lupus Erythematosus, Systemic</subject><subject>Mice</subject><subject>Microvasculature</subject><subject>Neostriatum</subject><subject>Neurological complications</subject><subject>Neuromodulation</subject><subject>Neuropeptides</subject><subject>Neuroprotection</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>PAC1 protein</subject><subject>Peptides</subject><subject>Pituitary adenylate cyclase-activating polypeptide</subject><subject>Pituitary Adenylate Cyclase-Activating Polypeptide - metabolism</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I - metabolism</subject><subject>Receptors, Vasoactive Intestinal Peptide, Type II</subject><subject>Receptors, Vasoactive Intestinal Polypeptide, Type I</subject><subject>Systemic lupus erythematosus</subject><subject>t-Plasminogen activator</subject><subject>Tissue plasminogen activator</subject><subject>Transcription factors</subject><subject>U-Plasminogen activator</subject><subject>Urokinase</subject><subject>Vascular cell adhesion molecule 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Hippocampal and Striatal Expression of Endothelial Markers and VIP/PACAP Neuropeptides in a Mouse Model of Systemic Lupus Erythematosus</title><author>Lee, Jayden ; Thomas Broome, Sarah ; Jansen, Margo Iris ; Mandwie, Mawj ; Logan, Grant J ; Marzagalli, Rubina ; Musumeci, Giuseppe ; Castorina, Alessandro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-c8f61999471b4fb2b403e3aac24079638bfb2b2b458d03461ba7335ccadb3e0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Age groups</topic><topic>Animals</topic><topic>Autoimmunity</topic><topic>Brain-derived neurotrophic factor</topic><topic>Central nervous system</topic><topic>Chronic conditions</topic><topic>Endothelium</topic><topic>Enzymes</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Hippocampus</topic><topic>Immunomodulation</topic><topic>Inflammation</topic><topic>Intercellular adhesion 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Jayden</au><au>Thomas Broome, Sarah</au><au>Jansen, Margo Iris</au><au>Mandwie, Mawj</au><au>Logan, Grant J</au><au>Marzagalli, Rubina</au><au>Musumeci, Giuseppe</au><au>Castorina, Alessandro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered Hippocampal and Striatal Expression of Endothelial Markers and VIP/PACAP Neuropeptides in a Mouse Model of Systemic Lupus Erythematosus</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2023-07-01</date><risdate>2023</risdate><volume>24</volume><issue>13</issue><spage>11118</spage><pages>11118-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most common and severe manifestations of lupus; however, its pathogenesis is still poorly understood. While there is sparse evidence suggesting that the ongoing autoimmunity may trigger pathogenic changes to the central nervous system (CNS) microvasculature, culminating in inflammatory/ischemic damage, further evidence is still needed. In this study, we used the spontaneous mouse model of SLE (NZBWF1 mice) to investigate the expression of genes and proteins associated with endothelial (dys)function: tissue and urokinase plasminogen activators (tPA and uPA), intercellular and vascular adhesion molecules 1 (ICAM-1 and VCAM-1), brain derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 4 (KLF4) and neuroprotection/immune modulation: pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), PACAP receptor (PAC1), VIP receptors 1 and 2 (VPAC1 and VPAC2). Analyses were carried out both in the hippocampus and striatum of SLE mice of two different age groups (2 and 7 months old), since age correlates with disease severity. In the hippocampus, we identified a gene/protein expression profile indicative of mild endothelial dysfunction, which increased in severity in aged SLE mice. These alterations were paralleled by moderate alterations in the expression of VIP, PACAP and related receptors. In contrast, we report a robust upregulation of endothelial activation markers in the striatum of both young and aged mice, concurrent with significant induction of the VIP/PACAP system. These data identify molecular signatures of endothelial alterations in the hippocampus and striatum of NZBWF1 mice, which are accompanied by a heightened expression of endogenous protective/immune-modulatory neuropeptides. Collectively, our results support the idea that NPSLE may cause alterations of the CNS micro-vascular compartment that cannot be effectively counteracted by the endogenous activity of the neuropeptides PACAP and VIP.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37446298</pmid><doi>10.3390/ijms241311118</doi><orcidid>https://orcid.org/0000-0002-5444-0920</orcidid><orcidid>https://orcid.org/0000-0002-4165-4276</orcidid><orcidid>https://orcid.org/0000-0002-8260-8890</orcidid><orcidid>https://orcid.org/0000-0001-7037-759X</orcidid><orcidid>https://orcid.org/0000-0003-0721-4055</orcidid><orcidid>https://orcid.org/0009-0000-5583-0579</orcidid><orcidid>https://orcid.org/0000-0001-9365-342X</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2023-07, Vol.24 (13), p.11118 |
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| source | PubMed Central (Open Access); MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Age groups Animals Autoimmunity Brain-derived neurotrophic factor Central nervous system Chronic conditions Endothelium Enzymes Gene expression Genetic aspects Hippocampus Immunomodulation Inflammation Intercellular adhesion molecule 1 Ischemia KLF4 protein Krueppel-like factor Lupus Lupus Erythematosus, Systemic Mice Microvasculature Neostriatum Neurological complications Neuromodulation Neuropeptides Neuroprotection Nitric oxide Nitric-oxide synthase PAC1 protein Peptides Pituitary adenylate cyclase-activating polypeptide Pituitary Adenylate Cyclase-Activating Polypeptide - metabolism Protein expression Proteins Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I - metabolism Receptors, Vasoactive Intestinal Peptide, Type II Receptors, Vasoactive Intestinal Polypeptide, Type I Systemic lupus erythematosus t-Plasminogen activator Tissue plasminogen activator Transcription factors U-Plasminogen activator Urokinase Vascular cell adhesion molecule 1 Vasoactive agents Vasoactive Intestinal Peptide - metabolism Vasoactive intestinal peptides |
| title | Altered Hippocampal and Striatal Expression of Endothelial Markers and VIP/PACAP Neuropeptides in a Mouse Model of Systemic Lupus Erythematosus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T17%3A22%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Altered%20Hippocampal%20and%20Striatal%20Expression%20of%20Endothelial%20Markers%20and%20VIP/PACAP%20Neuropeptides%20in%20a%20Mouse%20Model%20of%20Systemic%20Lupus%20Erythematosus&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Lee,%20Jayden&rft.date=2023-07-01&rft.volume=24&rft.issue=13&rft.spage=11118&rft.pages=11118-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms241311118&rft_dat=%3Cgale_pubme%3EA758317941%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2836448945&rft_id=info:pmid/37446298&rft_galeid=A758317941&rfr_iscdi=true |