Zu den Inhalten springen

Klinik für Psychiatrie und Psychotherapie

Former Research group Biber

"Neuroprotective function of microglia in NMDA-induced excitotoxicity in organotypic hippocampal brain slices"

Summary

Upon any type of central nervous system (CNS) injury microglia become rapidly activated, a process which has long been thought to be detrimental for neuronal survival. However, recent findings suggest that microglia display neuroprotective properties in various CNS pathologies. In the present study we determined the effect of microglia depletion on excitotoxicity-induced neurodegeneration using mouse organotypic hippocampal slice cultures. Treatment of slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA) induced a region-specific increase in neuronal cell death with CA1 neurons being most vulnerable to NMDA-exposure, followed by CA3 and DG neurons, respectively (CA1>CA3>DG). This selective neuronal vulnerability strongly correlated with activation of local microglia. At 10 μM NMDA, microglia activation was restricted to the CA1 region, while in the CA3 region changes in microglia morphology were only evident at 15 μM NMDA or higher. As DG neurons were most resistant to NMDA-excitotoxicity, microglia activation in this region was only observed at NMDA-concentrations of 25 μM or higher.

Interestingly, ablation of microglia by treatment of slice cultures with liposome-encapsulated clodronate, and subsequent exposure to NMDA, resulted in severely enhanced neuronal cell death in the CA3 and DG region. Particularly, the resistance of DG and CA3 neurons to NMDA-induced toxicity in the presence of ramified microglia, and the severely increased vulnerability of these neurons in the absence of microglia, suggests that ramified microglia contribute to the protection of neurons under pathological conditions.

Key References

  • Rooijen N, Boddeke HW, Biber K. (2012) Neuroprotective function for ramified microglia in hippocampal excitotoxicity. J Neuroinflammation. 2012 Jan 31;9(1):27
  • Hilmar R.J. van Weering, Hendrikus W.G.M. Boddeke, Jonathan Vinet, Nieske Brouwer, Alexander H. de Haas, Nico van Rooijen, Allan R. Thomsen, Knut Biber (2011) CXCL10/CXCR3 signaling in glia cells differentially affects NMDA-induced cell death in CA and DG neurons of the mouse hippocampus. Hippocampus, 21:220-32

Klinik für Psychiatrie und Psychotherapie

Hauptstraße 5
79104 Freiburg

Information: 0761 270-65010


Aktuelle Weiterbildung

PPA-Symposium 19.09.2020 "Psychiatrie und Psychotherapie – aktuell" (Infos und Anmeldung)


COH-FIT Studie

Nehmen Sie an einer internationalen Umfrage teil: https://www.coh-fit.com/


Informationen für den Umgang mit psychischen Belastungen im Zusammenhang mit der 'Corona-Krise'

Hier finden Sie eine Auswahl von Empfehlungen, die sich bei der Bewältigung besonderer Belastungen bewährt haben.


CORONA-Krise - Online-Unterstützung für Patienten mit Depression

Betroffene können sich formlos über die E-Mail-Adresse ifightdepression@deutsche-depressionshilfe.de für das Online-Programm iFightDepression anmelden und werden innerhalb von 24 Stunden freigeschaltet.