title: The Time Course of JNK and P38 Activation in Cerebellar Granule Neurons Following Glucose Deprivation and BDNF Treatment.
abstract: Low glucose condition induces neuronal cell-death via intracellular mechanisms including mitogen-activated protein kinases (MAPK) signaling pathways. It has been shown that low glucose medium decreases neuronal survival in cerebellar granule neurons (CGNs). In this study, we have examined the activation of JNK, p38kinase and ERK1/2 pathways in low glucose medium in CGNs. The CGNs were prepared from new-born (P-2 and P-5) rats and cultured in Dulbecco's Modified Eagle's Medium high (DMEM-HIGH) glucose supplemented with Fetal Bovine Serum (FBS) 10% for 7 days. The glucose deprivation was induced through replacing the culture medium with the low glucose (5 mM) medium. The MAPK pathways activation was evaluated through phospho specific antibodies using western blot. The viability of cells was measuring using MTT assay. The results indicated that low glucose reduces the cell survival and brain-derived neurotrophic factor (BDNF) elevates the cell viability in CGNs. The basal c-Jun N-terminal kinase (JNK) activity was high in CGNs and glucose deprivation for 24 h had increased phospho-JNK level to 2-fold compared to basal. BDNF treatment reduced the basal JNK activity within 30 min but had no effect in longer incubations. BDNF also blocked the low glucose-induced JNK activation. In addition, CGNs exhibited high p38 phosphorylation in low glucose medium in 48 h. These results demonstrated that in sustained low glucose conditions, CGNs had high activity of stress-activated MAPK which could induce cellular damage. Moreover, BDNF can prevent JNK and p38 activation in stress conditions and increase cell viability. Our results suggest that in sustained stress conditions, inhibition of JNK and/or p38 pathways might protect neurons from damage in low glucose conditions.
authors.affiliation: Department of Pharmacology-Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Niki
authors.initials: N
authors.lastname: Vakili Zahir
authors.forename: Mousa
authors.initials: M
authors.lastname: Abkhezr
authors.forename: Zahra
authors.initials: Z
authors.lastname: Khaje Piri
authors.forename: Seyyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.forename: Abbass
authors.initials: A
authors.lastname: Kebriaezade
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
keywords: Brain-derived neurotrophic factor; CGN; MAPKs; Signaling