034ea9df88a0c19ef11a0bf5db28977d antioxidants_a2021v10n10p1632.pdf 1bb64bbb5d624a539cb09f4964bc6afc936a7498 antioxidants_a2021v10n10p1632.pdf 11de5a6c21360a3fa8ab2f8cd0d6233b3a9dedce70f6b1c612049059893e4acc antioxidants_a2021v10n10p1632.pdf Title: The Recovery of Cognitive and Affective Deficiencies Linked with Chronic Osteoarthritis Pain and Implicated Pathways by Slow-Releasing Hydrogen Sulfide Treatment Subject: Chronic osteoarthritis pain is accompanied by several comorbidities whose treatment has not been completely resolved. The anti-inflammatory, analgesic, and antidepressant effects of slow-releasing hydrogen sulfide (H2S) donors during osteoarthritic pain have been shown, but their actions in the accompanying memory impairment and anxious-like behaviors have not yet been demonstrated. Using female mice with chronic osteoarthritic pain, the effects of natural, diallyl disulfide (DADS) or synthetic, morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137) slow-releasing H2S donors, on associated cognitive and grip strength deficits and anxiodepressive-like behaviors, were assessed. Their effects on specific brain areas implicated in the modulation of pain and emotional responses were also determined. Results demonstrated an improvement in memory and grip strength deficits, as well as in the anxious-like behaviors associated with chronic pain in GYY4137 and/or DADS treated mice. The painkiller and antidepressant properties of both treatments were also established. Treatment with DADS and/or GYY4137 inhibited: oxidative stress in the amygdala; phosphoinositide 3-kinase overexpression in the amygdala, periaqueductal gray matter, and anterior cingulate cortex; protein kinase B activation in the amygdala and infralimbic cortex; up-regulation of inducible nitric oxide synthase in the amygdala, periaqueductal gray matter and infralimbic cortex and apoptotic responses in the amygdala. These results might explain the recovery of memory and grip strength and the inhibition of allodynia and associated anxiodepressive-like behaviors by these treatments. In conclusion, this study revealed new properties of slow-releasing H2S donors in cognitive impairment and affective disorders linked with chronic osteoarthritis pain and their effects on the central nervous system. Keywords: anxiety; apoptosis; cognitive deficits; depression; grip strength impairments; hydrogen sulfide; osteoarthritic pain; oxidative stress Author: Gerad Batallé, Xue Bai, Enric Pouso-Vázquez, Gerad Roch, Laura Rodríguez and Olga Pol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Jan 20 07:51:58 2022 CET ModDate: Thu Jan 20 07:54:45 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3683307 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- HKBJPQ+VnURWPalladioL Type 1 Custom yes yes no 10 0 BMLKKL+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 JBTYHN+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 FPBYBF+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 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GLNOMM+PalatinoLinotype CID TrueType Identity-H yes yes yes 243 0 GLNOMN+PalatinoLinotype TrueType WinAnsi yes yes no 249 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:26:16 CEST RepresentationInformation: antioxidants_a2021v10n10p1632.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 11:58:53 CEST Size: 3683307 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 525 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Induction of Osteoarthritis Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Mechanical Allodynia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Measurement of Grip Strength Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Cognitive Behavior Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Depressive Behavioral Tests Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Anxiety Behavioral Tests Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Western Blot Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Experimental Procedures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Drugs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Children: Item: Title: Treatment with DADS and/or GYY4137 Inhibits Osteoarthritis-Induced Cognitive Impairment, Hind Limb Grip Strength Deficits and Mechanical Allodynia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: The Inhibition of the Anxiodepressive-Like Behaviors of DADS and GYY4137 in Animals with Chronic Osteoarthritis Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Effects of DADS and GYY4137 on the Protein Levels of 4-HNE, PI3K, p-Akt, NOS2 and BAX in the Amygdala of MIA-Injected Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Effects of DADS and GYY4137 on the Expression of 4-HNE, PI3K, p-Akt, NOS2 and BAX in the Periaqueductal Gray Matter of MIA-Injected Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Effects of DADS and GYY4137 on the Protein Levels of 4-HNE, PI3K, p-Akt, NOS2 and BAX in the Infralimbic Cortex of Mice with Osteoarthritic Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Effects of Treatment with DADS or GYY4137 on the Protein Levels of 4-HNE, PI3K, p-Akt, NOS2 and BAX in the Anterior Cingulate Cortex of MIA-Injected Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Info: Title: The Recovery of Cognitive and Affective Deficiencies Linked with Chronic Osteoarthritis Pain and Implicated Pathways by Slow-Releasing Hydrogen Sulfide Treatment Author: Gerad Batallé, Xue Bai, Enric Pouso-Vázquez, Gerad Roch, Laura Rodríguez and Olga Pol Subject: Chronic osteoarthritis pain is accompanied by several comorbidities whose treatment has not been completely resolved. The anti-inflammatory, analgesic, and antidepressant effects of slow-releasing hydrogen sulfide (H2S) donors during osteoarthritic pain have been shown, but their actions in the accompanying memory impairment and anxious-like behaviors have not yet been demonstrated. Using female mice with chronic osteoarthritic pain, the effects of natural, diallyl disulfide (DADS) or synthetic, morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137) slow-releasing H2S donors, on associated cognitive and grip strength deficits and anxiodepressive-like behaviors, were assessed. Their effects on specific brain areas implicated in the modulation of pain and emotional responses were also determined. Results demonstrated an improvement in memory and grip strength deficits, as well as in the anxious-like behaviors associated with chronic pain in GYY4137 and/or DADS treated mice. The painkiller and antidepressant properties of both treatments were also established. Treatment with DADS and/or GYY4137 inhibited: oxidative stress in the amygdala; phosphoinositide 3-kinase overexpression in the amygdala, periaqueductal gray matter, and anterior cingulate cortex; protein kinase B activation in the amygdala and infralimbic cortex; up-regulation of inducible nitric oxide synthase in the amygdala, periaqueductal gray matter and infralimbic cortex and apoptotic responses in the amygdala. These results might explain the recovery of memory and grip strength and the inhibition of allodynia and associated anxiodepressive-like behaviors by these treatments. In conclusion, this study revealed new properties of slow-releasing H2S donors in cognitive impairment and affective disorders linked with chronic osteoarthritis pain and their effects on the central nervous system. 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Annotations: Annotation: Subtype: Link Rect: 95, 710, 133, 720 Annotation: Subtype: Link Rect: 194, 676, 231, 686 Annotation: Subtype: Link Rect: 393, 640, 431, 651 Annotation: Subtype: Link Rect: 140, 607, 178, 617 Annotation: Subtype: Link Rect: 366, 583, 404, 594 Annotation: Subtype: Link Rect: 443, 560, 481, 571 Annotation: Subtype: Link Rect: 487, 560, 523, 571 Annotation: Subtype: Link Rect: 422, 537, 460, 548 Annotation: Subtype: Link Rect: 466, 537, 502, 548 Annotation: Subtype: Link Rect: 452, 514, 490, 525 Annotation: Subtype: Link Rect: 496, 514, 532, 525 Annotation: Subtype: Link Rect: 443, 491, 480, 502 Annotation: Subtype: Link Rect: 487, 491, 523, 502 Annotation: Subtype: Link Rect: 469, 468, 506, 479 Annotation: Subtype: Link Rect: 499, 433, 537, 444 Annotation: Subtype: Link Rect: 153, 400, 190, 410 Annotation: Subtype: Link Rect: 242, 377, 279, 387 Annotation: Subtype: Link Rect: 286, 377, 322, 387 Checksum: 93270bbd Type: CRC32 Checksum: 034ea9df88a0c19ef11a0bf5db28977d Type: MD5 Checksum: 1bb64bbb5d624a539cb09f4964bc6afc936a7498 Type: SHA-1