دورية أكاديمية
PNA5, A Novel Mas Receptor Agonist, Improves Neurovascular and Blood-Brain-Barrier Function in a Mouse Model of Vascular Cognitive Impairment and Dementia.
| العنوان: | PNA5, A Novel Mas Receptor Agonist, Improves Neurovascular and Blood-Brain-Barrier Function in a Mouse Model of Vascular Cognitive Impairment and Dementia. |
|---|---|
| المؤلفون: | Hoyer-Kimura C; Department of Physiology, The University of Arizona, Tucson, AZ 85724, USA., Hay M; Department of Physiology, The University of Arizona, Tucson, AZ 85724, USA.; Evelyn F. McKnight Brain Institute, The University of Arizona, Tucson, AZ 85724, USA.; ProNeurogen, Inc, Tucson, AZ, USA., Konhilas JP; Department of Physiology, The University of Arizona, Tucson, AZ 85724, USA., Morrison HW; College of Nursing, The University of Arizona, Tucson, AZ 85724, USA., Methajit M; Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ 85724, USA., Strom J; Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ 85724, USA., Polt R; Department of Chemistry and Biochemistry, The University of Arizona, Tucson, AZ 85724, USA., Salcedo V; Department of Physiology, The University of Arizona, Tucson, AZ 85724, USA., Fricks JP; ProNeurogen, Inc, Tucson, AZ, USA., Kalya A; Department of Physiology, The University of Arizona, Tucson, AZ 85724, USA., Pires PW; Department of Physiology, The University of Arizona, Tucson, AZ 85724, USA. |
| المصدر: | Aging and disease [Aging Dis] 2024 Aug 01; Vol. 15 (4), pp. 1927-1951. Date of Electronic Publication: 2024 Aug 01. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: JKL International Country of Publication: United States NLM ID: 101540533 Publication Model: Electronic Cited Medium: Internet ISSN: 2152-5250 (Electronic) Linking ISSN: 21525250 NLM ISO Abbreviation: Aging Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: California : JKL International |
| مواضيع طبية MeSH: | Blood-Brain Barrier*/drug effects , Blood-Brain Barrier*/metabolism , Disease Models, Animal* , Proto-Oncogene Mas* , Mice, Inbred C57BL*, Animals ; Mice ; Male ; Dementia, Vascular/drug therapy ; Dementia, Vascular/pathology ; Cognitive Dysfunction/drug therapy ; Cognitive Dysfunction/etiology ; Heart Failure/drug therapy ; Heart Failure/pathology ; Receptors, G-Protein-Coupled/agonists ; Receptors, G-Protein-Coupled/metabolism ; Microglia/drug effects ; Microglia/metabolism ; Microglia/pathology ; Peptide Fragments/pharmacology ; Cerebrovascular Circulation/drug effects |
| مستخلص: | It is well established that decreased brain blood flow, increased reactive oxygen species production (ROS), and pro-inflammatory mechanisms accelerate neurodegenerative disease progressions, including vascular cognitive impairment and dementia (VCID). Previous studies in our laboratory have shown that our novel glycosylated Angiotensin-(1-7) Mas receptor agonist PNA5 reverses cognitive deficits, decreases ROS production, and inhibits inflammatory cytokine production in our preclinical mouse model of VCID that is induced by chronic heart failure (VCID-HF). In the present study, the effects of VCID-HF and treatment with PNA5 on microglia activation, blood-brain-barrier (BBB) integrity, and neurovascular coupling were assessed in our mouse model of VCID-HF. Three-month-old male C57BL/6J mice were subjected to myocardial infarction (MI) to induce heart failure for four weeks and then treated with subcutaneous injections of extended-release PNA5. Microglia activation, BBB permeability, cerebral perfusion, and neurovascular coupling were assessed. Results show that in our VCID-HF model, there was an increase in microglial activation and recruitment within the CA1 and CA3 regions of the hippocampus, a disruption in BBB integrity, and a decrease in neurovascular coupling. Treatment with PNA5 reversed these neuropathological effects of VCID-HF, suggesting that PNA5 may be an effective disease-modifying therapy to treat and prevent VCID. This study identifies potential mechanisms by which heart failure may induce VCID and highlights the possible mechanisms by which treatment with our novel glycosylated Angiotensin-(1-7) Mas receptor agonist, PNA5, may protect cognitive function in our model of VCID. |
| References: | Nature. 2020 May;581(7806):71-76. (PMID: 32376954) Glia. 2012 May;60(5):717-27. (PMID: 22290798) Dement Geriatr Cogn Disord. 2007;24(6):418-23. (PMID: 17938570) Eur J Heart Fail. 2017 Feb;19(2):261-268. (PMID: 27862767) Nat Neurosci. 2018 Oct;21(10):1380-1391. (PMID: 30224810) Sci Rep. 2020 May 14;10(1):7979. (PMID: 32409672) J Inflamm Res. 2022 May 25;15:3083-3094. (PMID: 35642214) Elife. 2022 Jan 11;11:. (PMID: 35014950) Am J Physiol Heart Circ Physiol. 2022 Nov 1;323(5):H845-H860. (PMID: 36149767) Mol Neurobiol. 2016 Mar;53(2):1181-1194. (PMID: 25598354) Int J Mol Sci. 2020 Aug 19;21(17):. (PMID: 32825077) Postepy Hig Med Dosw. 1996;50(5):493-503. (PMID: 9072765) Hypertension. 2006 Mar;47(3):515-21. (PMID: 16365192) Front Behav Neurosci. 2022 Aug 04;16:903980. (PMID: 35990729) Circulation. 2000 Jun 27;101(25):2981-8. (PMID: 10869273) Neuroimage. 2010 Jul 15;51(4):1367-77. (PMID: 20350606) J Vis Exp. 2018 Jun 5;(136):. (PMID: 29939190) J Pharmacol Exp Ther. 2019 Apr;369(1):9-25. (PMID: 30709867) Behav Neurosci. 2017 Feb;131(1):99-114. (PMID: 28054808) Biomedicines. 2021 Jul 06;9(7):. (PMID: 34356845) Front Immunol. 2022 Feb 03;13:837250. (PMID: 35185929) Front Chem. 2015 Jun 24;3:40. (PMID: 26157795) Antioxid Redox Signal. 2011 Sep 1;15(5):1305-23. (PMID: 21294658) Trends Cardiovasc Med. 2014 May;24(4):165-9. (PMID: 24373981) CNS Neurosci Ther. 2019 Dec;25(12):1318-1328. (PMID: 31749316) Nat Immunol. 2016 Jul;17(7):797-805. (PMID: 27135602) Neurosci Lett. 1990 Jul 3;114(2):147-53. (PMID: 2203997) Brain Res. 2009 Apr 17;1266:29-36. (PMID: 19249294) Neuropharmacology. 2013 Aug;71:154-63. (PMID: 23583926) J Physiol. 2020 Jan;598(1):33-59. (PMID: 31671478) Brain Behav Immun. 2011 Feb;25(2):181-213. (PMID: 20970492) J Neuroinflammation. 2004 Jul 30;1(1):14. (PMID: 15285801) J Exp Med. 2022 Mar 7;219(3):. (PMID: 35201268) Neuroscience. 2014 Jul 25;273:39-51. (PMID: 24814023) J Neuroinflammation. 2013 Jan 11;10:4. (PMID: 23311642) J Neuroinflammation. 2021 Feb 22;18(1):58. (PMID: 33618737) Pharmaceuticals (Basel). 2014 Nov 25;7(12):1028-48. (PMID: 25429645) J Neurol Neurosurg Psychiatry. 2001 Jan;70(1):109-12. (PMID: 11118258) Nat Rev Neurol. 2018 Mar;14(3):133-150. (PMID: 29377008) Mol Psychiatry. 2022 Jun;27(6):2659-2673. (PMID: 35361905) Stroke. 2001 Nov;32(11):2530-3. (PMID: 11692012) J Neuroimaging. 2005 Apr;15(2):150-6. (PMID: 15746227) Curr Neuropharmacol. 2020;18(12):1237-1249. (PMID: 32469699) Brain Pathol. 2018 Nov;28(6):791-805. (PMID: 29222823) Mayo Clin Proc. 1994 Jul;69(7):664-74. (PMID: 8015331) J Neuroinflammation. 2021 Oct 15;18(1):236. (PMID: 34654436) Brain Behav Immun. 2010 Feb;24(2):243-53. (PMID: 19825412) J Alzheimers Dis. 2010;21(1):1-14. (PMID: 20182045) Front Physiol. 2018 Jul 03;9:806. (PMID: 30018565) Acta Neuropathol. 2020 Dec;140(6):793-810. (PMID: 32865691) Am J Med. 2005 May;118(5):496-502. (PMID: 15866252) J Vis Exp. 2018 Feb 26;(132):. (PMID: 29553506) J Cell Biol. 2018 Feb 5;217(2):459-472. (PMID: 29196460) Front Cell Neurosci. 2017 Aug 08;11:235. (PMID: 28848398) Neuron. 2017 Sep 27;96(1):17-42. (PMID: 28957666) Stroke. 2016 Jul;47(7):1953-9. (PMID: 27301939) Alzheimers Dement. 2019 Jan;15(1):158-167. (PMID: 30642436) Sci Rep. 2017 Oct 16;7(1):13211. (PMID: 29038483) J Neurosci. 2013 Feb 6;33(6):2481-93. (PMID: 23392676) Nature. 2022 Mar;603(7903):885-892. (PMID: 35165441) Handb Clin Neurol. 2015;127:3-13. (PMID: 25702206) Nat Protoc. 2010 Feb;5(2):201-8. (PMID: 20134419) Congest Heart Fail. 2013 Mar-Apr;19(2):92-8. (PMID: 23057677) Brain Sci. 2020 Oct 07;10(10):. (PMID: 33036338) Psychoneuroendocrinology. 2013 Oct;38(10):2196-208. (PMID: 23664267) Arch Intern Med. 2006 May 8;166(9):1003-8. (PMID: 16682574) Nat Commun. 2021 May 27;12(1):3190. (PMID: 34045465) J Mol Med (Berl). 1997 Feb;75(2):130-8. (PMID: 9083930) Drug Des Devel Ther. 2020 Apr 16;14:1523-1534. (PMID: 32368011) Growth Factors. 2016 Feb;34(1-2):11-8. (PMID: 27055565) Sci Rep. 2022 Feb 2;12(1):1806. (PMID: 35110632) J Immunol. 2020 Jan 15;204(2):286-293. (PMID: 31907271) Curr Drug Deliv. 2005 Jan;2(1):59-73. (PMID: 16305409) Br J Pharmacol. 2012 Dec;167(7):1520-32. (PMID: 22817481) Nature. 2021 May;593(7858):255-260. (PMID: 33911285) J Am Heart Assoc. 2018 Mar 26;7(7):. (PMID: 29581224) Eur Heart J. 2012 Jul;33(14):1769-76. (PMID: 22296945) Mol Neurobiol. 2017 Dec;54(10):7567-7584. (PMID: 27830532) Nat Rev Neurosci. 2020 Aug;21(8):416-432. (PMID: 32636528) J Neuroinflammation. 2013 Jun 21;10:75. (PMID: 23786632) J Cereb Blood Flow Metab. 2020 Dec;40(1_suppl):S6-S24. (PMID: 32928017) Metab Brain Dis. 2015 Apr;30(2):393-400. (PMID: 24733573) J Med Chem. 2008 Aug 28;51(16):4881-9. (PMID: 18666771) ILAR J. 2011;52(3):e21-31. (PMID: 21677360) J Neuropathol Exp Neurol. 2010 Sep;69(9):896-909. (PMID: 20720507) Front Cell Neurosci. 2013 Jan 30;7:3. (PMID: 23386810) J Neurochem. 2018 Mar;144(5):644-650. (PMID: 29222909) Glia. 2012 Oct;60(10):1506-17. (PMID: 22740309) Elife. 2021 Feb 26;10:. (PMID: 33635784) Front Neurosci. 2023 Jul 12;17:1184049. (PMID: 37502683) |
| معلومات مُعتمدة: | R01 AG073230 United States AG NIA NIH HHS; U01 AG066623 United States AG NIA NIH HHS |
| المشرفين على المادة: | 0 (Proto-Oncogene Mas) 0 (Receptors, G-Protein-Coupled) 0 (Peptide Fragments) |
| تواريخ الأحداث: | Date Created: 20231010 Date Completed: 20240725 Latest Revision: 20240802 |
| رمز التحديث: | 20240802 |
| مُعرف محوري في PubMed: | PMC11272189 |
| DOI: | 10.14336/AD.2023.0928 |
| PMID: | 37815905 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2152-5250 |
|---|---|
| DOI: | 10.14336/AD.2023.0928 |