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Sökning: WFRF:(Brundin Patrik) > Exendin-4 Treatment...

  • Ventorp, FilipLund University,Lunds universitet,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine (författare)

Exendin-4 Treatment Improves LPS-Induced Depressive-Like Behavior Without Affecting ProInflammatory Cytokines

  • Artikel/kapitelEngelska2017

Förlag, utgivningsår, omfång ...

  • IOS Press,2017
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:umu-135989
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-135989URI
  • https://doi.org/10.3233/JPD-171068DOI
  • https://lup.lub.lu.se/record/81ea3183-835e-40d3-b0be-3313c24c7537URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Background: Exendin-4 is a peptide agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently in clinical trials as a potential disease-modifying therapy for Parkinson's disease. In light of this, it is important to understand potential modes of action of exendin-4 in the brain. Exendin-4 is neuroprotective and has been proposed to be directly anti-inflammatory, and that this is one way it reduces neurodegeneration. However, prior studies have focused on animal models involving both neurodegeneration and inflammation, therefore, it is also possible that the observed decreased inflammation is secondary to reduced neurodegeneration. Objective: To investigate whether exendin-4 directly reduces inflammation in the brain following an insult that involves neuroinflammation but not neurodegeneration, namely systemic administration of lipopolysaccharide (LPS). Methods: Rats were administered LPS systemically and were treated with either 0.5 mu g/kg exendin-4 or saline vehicle injections over 5 days. Behavior was evaluated with forced swim test. We assayed TNF-alpha and IL-1 beta levels in cerebrospinal fluid and cytokine mRNA expression in striatal, hippocampal and cortical tissues using qPCR. We determined brain monoamines using high-performance liquid chromatography. Finally, we isolated primary brain microglia from rats and measured cytokine production after exendin-4 treatment and LPS stimulation. Results: Exendin-4 treatment did not affect cytokine mRNA expression in brain, cytokine levels in cerebrospinal fluid or cytokine production from cultured microglia, although there was a trend towards increased striatal dopamine. Importantly, exendin-4 significantly prevented depressive-like behavior at 24 hours after LPS injection, indicating that the drug engaged a target in the brain. Depressive-like behavior was associated with altered dopamine turnover in the striatum. Conclusion: We did not detect any anti-inflammatory effects of exendin-4. In previous studies exploring the effects of exendin-4 on brain insults involving neurodegeneration, observations of reduced inflammation might have been secondary to mitigation of neuronal death. Our results indicate that the effects of exendin-4 on behavior may be due to effects on dopamine synthesis or metabolism.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Bay-Richter, CecilieAarhus University(Swepub:lu)med-cbc (författare)
  • Nagendra, Analise SauroVan Andel Research Institute (författare)
  • Janelidze, ShorenaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)nkir-sje (författare)
  • Sjödahl Matsson, ViktorLund University (författare)
  • Lipton, JackMichigan State University (författare)
  • Nordström, UlrikaUmeå University,Umeå universitet,Klinisk neurovetenskap(Swepub:lu)med-uan (författare)
  • Westrin, AsaLund University,Lunds universitet,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pski-awe (författare)
  • Brundin, PatrikLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)mphy-pbr (författare)
  • Brundin, LenaLund University,Lunds universitet,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)mphy-lla (författare)
  • Psykiatri, LundSektion IV (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Parkinson's Disease: IOS Press7:2, s. 263-2731877-71711877-718X

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