Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice

Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 7...
Ausführliche Beschreibung

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Autor*in:	Xu, Jingyi [verfasserIn] Yang, Chunshu Zeng, Siyuan Wang, Xuejiao Yang, Pingting Qin, Ling

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Neuropsychiatric systemic lupus erythematosus Glucose regulatory protein 78 Microglia Spatial memory Rapamycin

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Journal of neuroinflammation - London : BioMed Central, 2004, 20(2023), 1 vom: 26. Juni
Übergeordnetes Werk:	volume:20 ; year:2023 ; number:1 ; day:26 ; month:06

Links:	Volltext

DOI / URN:	10.1186/s12974-023-02832-8

Katalog-ID:	SPR052057453

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520			\|a Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.
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allfields	10.1186/s12974-023-02832-8 doi (DE-627)SPR052057453 (SPR)s12974-023-02832-8-e DE-627 ger DE-627 rakwb eng Xu, Jingyi verfasserin aut Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE. Neuropsychiatric systemic lupus erythematosus (dpeaa)DE-He213 Glucose regulatory protein 78 (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Spatial memory (dpeaa)DE-He213 Rapamycin (dpeaa)DE-He213 Yang, Chunshu aut Zeng, Siyuan aut Wang, Xuejiao aut Yang, Pingting aut Qin, Ling aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 26. Juni (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:26 month:06 https://dx.doi.org/10.1186/s12974-023-02832-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2023 1 26 06
spelling	10.1186/s12974-023-02832-8 doi (DE-627)SPR052057453 (SPR)s12974-023-02832-8-e DE-627 ger DE-627 rakwb eng Xu, Jingyi verfasserin aut Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE. Neuropsychiatric systemic lupus erythematosus (dpeaa)DE-He213 Glucose regulatory protein 78 (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Spatial memory (dpeaa)DE-He213 Rapamycin (dpeaa)DE-He213 Yang, Chunshu aut Zeng, Siyuan aut Wang, Xuejiao aut Yang, Pingting aut Qin, Ling aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 26. Juni (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:26 month:06 https://dx.doi.org/10.1186/s12974-023-02832-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2023 1 26 06
allfields_unstemmed	10.1186/s12974-023-02832-8 doi (DE-627)SPR052057453 (SPR)s12974-023-02832-8-e DE-627 ger DE-627 rakwb eng Xu, Jingyi verfasserin aut Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE. Neuropsychiatric systemic lupus erythematosus (dpeaa)DE-He213 Glucose regulatory protein 78 (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Spatial memory (dpeaa)DE-He213 Rapamycin (dpeaa)DE-He213 Yang, Chunshu aut Zeng, Siyuan aut Wang, Xuejiao aut Yang, Pingting aut Qin, Ling aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 26. Juni (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:26 month:06 https://dx.doi.org/10.1186/s12974-023-02832-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2023 1 26 06
allfieldsGer	10.1186/s12974-023-02832-8 doi (DE-627)SPR052057453 (SPR)s12974-023-02832-8-e DE-627 ger DE-627 rakwb eng Xu, Jingyi verfasserin aut Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE. Neuropsychiatric systemic lupus erythematosus (dpeaa)DE-He213 Glucose regulatory protein 78 (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Spatial memory (dpeaa)DE-He213 Rapamycin (dpeaa)DE-He213 Yang, Chunshu aut Zeng, Siyuan aut Wang, Xuejiao aut Yang, Pingting aut Qin, Ling aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 26. Juni (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:26 month:06 https://dx.doi.org/10.1186/s12974-023-02832-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2023 1 26 06
allfieldsSound	10.1186/s12974-023-02832-8 doi (DE-627)SPR052057453 (SPR)s12974-023-02832-8-e DE-627 ger DE-627 rakwb eng Xu, Jingyi verfasserin aut Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE. Neuropsychiatric systemic lupus erythematosus (dpeaa)DE-He213 Glucose regulatory protein 78 (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Spatial memory (dpeaa)DE-He213 Rapamycin (dpeaa)DE-He213 Yang, Chunshu aut Zeng, Siyuan aut Wang, Xuejiao aut Yang, Pingting aut Qin, Ling aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 26. Juni (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:26 month:06 https://dx.doi.org/10.1186/s12974-023-02832-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2023 1 26 06
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The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Neuropsychiatric systemic lupus erythematosus</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glucose regulatory protein 78</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Microglia</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Spatial memory</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rapamycin</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yang, Chunshu</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zeng, Siyuan</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, Xuejiao</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yang, Pingting</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Qin, Ling</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Journal of neuroinflammation</subfield><subfield code="d">London : BioMed Central, 2004</subfield><subfield code="g">20(2023), 1 vom: 26. 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author	Xu, Jingyi
spellingShingle	Xu, Jingyi misc Neuropsychiatric systemic lupus erythematosus misc Glucose regulatory protein 78 misc Microglia misc Spatial memory misc Rapamycin Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice
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topic_title	Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice Neuropsychiatric systemic lupus erythematosus (dpeaa)DE-He213 Glucose regulatory protein 78 (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Spatial memory (dpeaa)DE-He213 Rapamycin (dpeaa)DE-He213
topic	misc Neuropsychiatric systemic lupus erythematosus misc Glucose regulatory protein 78 misc Microglia misc Spatial memory misc Rapamycin
topic_unstemmed	misc Neuropsychiatric systemic lupus erythematosus misc Glucose regulatory protein 78 misc Microglia misc Spatial memory misc Rapamycin
topic_browse	misc Neuropsychiatric systemic lupus erythematosus misc Glucose regulatory protein 78 misc Microglia misc Spatial memory misc Rapamycin
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title	Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice
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title_full	Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice
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author_browse	Xu, Jingyi Yang, Chunshu Zeng, Siyuan Wang, Xuejiao Yang, Pingting Qin, Ling
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title_sort	disturbance of neuron–microglia crosstalk mediated by grp78 in neuropsychiatric systemic lupus erythematosus mice
title_auth	Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice
abstract	Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE. © The Author(s) 2023
abstractGer	Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE. © The Author(s) 2023
abstract_unstemmed	Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE. © The Author(s) 2023
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title_short	Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice
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The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. 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Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice

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