Purine nucleosides support the neurite outgrowth of primary rat cerebellar granule cells after hypoxia.
Mammalian neurons require a constant supply of oxygen to maintain adequate cellular functions and survival. Following sustained hypoxia during ischemic events in brain, the energy status of neurons and glia is compromised, which may subsequently lead to cell death by apoptosis and necrosis. Concomitant with energy depletion is the formation of the purine nucleoside adenosine, a powerful endogenous neuroprotectant. In this paper the effect of chemical hypoxia on cell survival and neurite outgrowth of primary cerebellar granule cells was investigated. Rotenone, a mitochondrial complex I inhibitor, induced a 30.4 +/- 3.6% loss of viable cells and a 35.0 +/- 4.4% loss of neurite formation of cerebellar granule cells, which was partially restored by the addition of purine nucleosides adenosine, inosine and guanosine. Inosine had the most striking effect of 37.7 +/- 2.9% rescue of viability and 71.2 +/- 18.4% rescue of neurite outgrowth. Data confirm the suggested role of purine nucleosides for the neuronal regeneration of primary brain cells following hypoxic insult.
Böcklinger
Karl
K
Institute for Medical Chemistry and Biochemistry, Department of Neurobiochemistry, University of Innsbruck, Fritz Pregl Str. 3, A-6020 Innsbruck, Austria.
Tomaselli
Bettina
B
Heftberger
Veronika
V
Podhraski
Valerie
V
Bandtlow
Christine
C
Baier-Bitterlich
Gabriele
G
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D006151:Guanosine / Q000494:pharmacology; D007288:Inosine / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011684:Purine Nucleosides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000494:pharmacology; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology
D018696:Neuroprotective Agents; D011684:Purine Nucleosides; D014475:Uncoupling Agents; D012402:Rotenone; D006151:Guanosine; D007288:Inosine; D000241:Adenosine