Distinct regulation of nNOS and iNOS by CB 2 receptor in remote delayed neurodegeneration

S. Oddi, L. Latini, M. T. Viscomi, E. Bisicchia, M. Molinari, M. Maccarrone

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Hemicerebellectomy results in remote delayed degeneration of precerebellar neurons. We have reported that such a lesion induces type 2 cannabinoid receptor (CB2) expression in precerebellar neurons and that stimulation of CB2, but not CB1, has neuroprotective effects. In this study, we found that in the same model, the CB 2 agonist JWH-015 enhances neuronal nitric oxide synthase (nNOS) expression in axotomized neurons and that CB2-mediated neuroprotection is abrogated by pharmacological inhibition of nNOS. JWH-015 prevented the axotomy-induced upregulation of inducible NOS (iNOS) in astrocytes but had no effect on endothelial NOS (eNOS). In addition, we observed that JWH-015 significantly reduces hemicerebellectomyinduced neuroinflammatory responses and oxidative/nitrative stress. With regard to the signaling pathways of CB2/nNOSmediated neuroprotection, we noted nNOS-dependent modulation of the expression of anti-oxidative (Hsp70) and anti-apoptotic (Bcl-2) proteins. These findings shed light on the interactions between the endocannabinoid and nitrergic systems after focal brain injury, implicating distinct functions of nNOS activation and iNOS inhibition in CB 2 signaling, which protect neurons from axotomy-induced cell death.

Original languageEnglish
Pages (from-to)371-387
Number of pages17
JournalJournal of Molecular Medicine
Volume90
Issue number4
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Nitric Oxide Synthase Type I
Axotomy
Neurons
Cannabinoid Receptor CB2
Nerve Degeneration
Endocannabinoids
Neuroprotective Agents
Astrocytes
Brain Injuries
Oxidative Stress
Cell Death
Up-Regulation
Pharmacology
JHW 015
Proteins
Neuroprotection

Keywords

  • Cannabinoids
  • Neurodegeneration
  • Nitric oxide
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this

Distinct regulation of nNOS and iNOS by CB 2 receptor in remote delayed neurodegeneration. / Oddi, S.; Latini, L.; Viscomi, M. T.; Bisicchia, E.; Molinari, M.; Maccarrone, M.

In: Journal of Molecular Medicine, Vol. 90, No. 4, 04.2012, p. 371-387.

Research output: Contribution to journalArticle

Oddi, S. ; Latini, L. ; Viscomi, M. T. ; Bisicchia, E. ; Molinari, M. ; Maccarrone, M. / Distinct regulation of nNOS and iNOS by CB 2 receptor in remote delayed neurodegeneration. In: Journal of Molecular Medicine. 2012 ; Vol. 90, No. 4. pp. 371-387.
@article{24bf1750f3934f6b9ed9c237ab63b040,
title = "Distinct regulation of nNOS and iNOS by CB 2 receptor in remote delayed neurodegeneration",
abstract = "Hemicerebellectomy results in remote delayed degeneration of precerebellar neurons. We have reported that such a lesion induces type 2 cannabinoid receptor (CB2) expression in precerebellar neurons and that stimulation of CB2, but not CB1, has neuroprotective effects. In this study, we found that in the same model, the CB 2 agonist JWH-015 enhances neuronal nitric oxide synthase (nNOS) expression in axotomized neurons and that CB2-mediated neuroprotection is abrogated by pharmacological inhibition of nNOS. JWH-015 prevented the axotomy-induced upregulation of inducible NOS (iNOS) in astrocytes but had no effect on endothelial NOS (eNOS). In addition, we observed that JWH-015 significantly reduces hemicerebellectomyinduced neuroinflammatory responses and oxidative/nitrative stress. With regard to the signaling pathways of CB2/nNOSmediated neuroprotection, we noted nNOS-dependent modulation of the expression of anti-oxidative (Hsp70) and anti-apoptotic (Bcl-2) proteins. These findings shed light on the interactions between the endocannabinoid and nitrergic systems after focal brain injury, implicating distinct functions of nNOS activation and iNOS inhibition in CB 2 signaling, which protect neurons from axotomy-induced cell death.",
keywords = "Cannabinoids, Neurodegeneration, Nitric oxide, Oxidative stress",
author = "S. Oddi and L. Latini and Viscomi, {M. T.} and E. Bisicchia and M. Molinari and M. Maccarrone",
year = "2012",
month = "4",
doi = "10.1007/s00109-011-0846-z",
language = "English",
volume = "90",
pages = "371--387",
journal = "Journal of Molecular Medicine",
issn = "0946-2716",
publisher = "Springer Verlag",
number = "4",

}

TY - JOUR

T1 - Distinct regulation of nNOS and iNOS by CB 2 receptor in remote delayed neurodegeneration

AU - Oddi, S.

AU - Latini, L.

AU - Viscomi, M. T.

AU - Bisicchia, E.

AU - Molinari, M.

AU - Maccarrone, M.

PY - 2012/4

Y1 - 2012/4

N2 - Hemicerebellectomy results in remote delayed degeneration of precerebellar neurons. We have reported that such a lesion induces type 2 cannabinoid receptor (CB2) expression in precerebellar neurons and that stimulation of CB2, but not CB1, has neuroprotective effects. In this study, we found that in the same model, the CB 2 agonist JWH-015 enhances neuronal nitric oxide synthase (nNOS) expression in axotomized neurons and that CB2-mediated neuroprotection is abrogated by pharmacological inhibition of nNOS. JWH-015 prevented the axotomy-induced upregulation of inducible NOS (iNOS) in astrocytes but had no effect on endothelial NOS (eNOS). In addition, we observed that JWH-015 significantly reduces hemicerebellectomyinduced neuroinflammatory responses and oxidative/nitrative stress. With regard to the signaling pathways of CB2/nNOSmediated neuroprotection, we noted nNOS-dependent modulation of the expression of anti-oxidative (Hsp70) and anti-apoptotic (Bcl-2) proteins. These findings shed light on the interactions between the endocannabinoid and nitrergic systems after focal brain injury, implicating distinct functions of nNOS activation and iNOS inhibition in CB 2 signaling, which protect neurons from axotomy-induced cell death.

AB - Hemicerebellectomy results in remote delayed degeneration of precerebellar neurons. We have reported that such a lesion induces type 2 cannabinoid receptor (CB2) expression in precerebellar neurons and that stimulation of CB2, but not CB1, has neuroprotective effects. In this study, we found that in the same model, the CB 2 agonist JWH-015 enhances neuronal nitric oxide synthase (nNOS) expression in axotomized neurons and that CB2-mediated neuroprotection is abrogated by pharmacological inhibition of nNOS. JWH-015 prevented the axotomy-induced upregulation of inducible NOS (iNOS) in astrocytes but had no effect on endothelial NOS (eNOS). In addition, we observed that JWH-015 significantly reduces hemicerebellectomyinduced neuroinflammatory responses and oxidative/nitrative stress. With regard to the signaling pathways of CB2/nNOSmediated neuroprotection, we noted nNOS-dependent modulation of the expression of anti-oxidative (Hsp70) and anti-apoptotic (Bcl-2) proteins. These findings shed light on the interactions between the endocannabinoid and nitrergic systems after focal brain injury, implicating distinct functions of nNOS activation and iNOS inhibition in CB 2 signaling, which protect neurons from axotomy-induced cell death.

KW - Cannabinoids

KW - Neurodegeneration

KW - Nitric oxide

KW - Oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=84862532130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862532130&partnerID=8YFLogxK

U2 - 10.1007/s00109-011-0846-z

DO - 10.1007/s00109-011-0846-z

M3 - Article

C2 - 22198001

AN - SCOPUS:84862532130

VL - 90

SP - 371

EP - 387

JO - Journal of Molecular Medicine

JF - Journal of Molecular Medicine

SN - 0946-2716

IS - 4

ER -