Hippocampus and cerebral cortex present a different autophagic response after oxygen and glucose deprivation in an ex vivo rat brain slice model
Article first published online: 13 MAY 2015
© 2014 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 41, Issue 4, pages e68–e79, June 2015
How to Cite
Pérez-Rodríguez, D., Anuncibay-Soto, B., Llorente, I. L., Pérez-García, C. C. and Fernández-López, A. (2015), Hippocampus and cerebral cortex present a different autophagic response after oxygen and glucose deprivation in an ex vivo rat brain slice model. Neuropathology and Applied Neurobiology, 41: e68–e79. doi: 10.1111/nan.12152
- Issue published online: 13 MAY 2015
- Article first published online: 13 MAY 2015
- Accepted manuscript online: 25 MAY 2014 11:19PM EST
- Manuscript Accepted: 21 MAY 2014
- Manuscript Received: 20 JAN 2014
- Junta de Castilla y León, Spain. Grant Numbers: LE184A12-2, EDU/346/2013
To evaluate the neuroprotective role of autophagy in the cerebral cortex and hippocampus using an ex vivo animal model of stroke in brain slices.
Brain slices were maintained for 30 min in oxygen and glucose deprivation (OGD) followed by 3 h in normoxic conditions to simulate the reperfusion that follows ischaemia in vivo (RL, reperfusion-like). Phagophore formation (Beclin 1 and LC3B) as well as autophagy flux (p62/SQSTM1, Atg5, Atg7 and polyubiquitin) markers were quantified by Western blot and/or qPCR. The release of lactate dehydrogenase (LDH) and glutamate in the medium was used as a measure of the mortality in the absence and in the presence of the autophagy inhibitor 3-methyladenine.
Striking differences in the autophagy markers were observed between the hippocampus and cerebral cortex in normoxic conditions. OGD/RL induced increases both in the phagophore formation and in the autophagy flux in the first three hours in the cerebral cortex that were not observed in the hippocampus. The blocking of autophagy increased the OGD/RL-induced mortality, increased the glutamate release in both the cerebral cortex and hippocampus and abolished the OGD-induced decrease in the polyubiquitinated proteins in the cerebral cortex.
We conclude that OGD induces a rapid autophagic response in the cerebral cortex that plays a neuroprotective role. Polyubiquitination levels and control of the glutamate release appear to be involved in the neuroprotective role of autophagy.