title: Mitochondrial dynamics associated with oxygen-glucose deprivation in rat primary neuronal cultures.
abstract: Our objective was to investigate the mitochondrial dynamics following oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. We documented changes in morphology, protein expression, and DNA levels in mitochondria following OGD and examined the roles of mitochondrial fission [dynamin-related protein 1 (Drp1), fission protein-1 (Fis1)] and fusion [mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy-1 protein (OPA1)] proteins on mitochondrial biogenesis and morphogenesis. We tested the effects of two Drp1 blockers [15-deoxy-Δ12,14-Prostaglandin J2 (PGJ2) and Mitochondrial Division Inhibitor (Mdivi-1)] on mitochondrial dynamics and cell survival. One hour of OGD had minimal effects on neuronal viability but mitochondria appeared condensed. Three hours of OGD caused a 60% decrease in neuronal viability accompanied by a transition from primarily normal/tubular and lesser number of rounded mitochondria during normoxia to either poorly labeled or small and large rounded mitochondria. The percentage of rounded mitochondria remained the same. The mitochondrial voltage-dependent anion channel, Complex V, and mitoDNA levels increased after OGD associated with a dramatic reduction in Drp1 expression, less reduction in Mfn2 expression, an increase in Mfn1 expression, with no changes in either OPA1 or Fis1. Although PGJ2 increased polymerization of Drp1, it did not reduce cell death or alter mitochondrial morphology following OGD and Mdivi-1 did not protect neurons against OGD. In summary, mitochondrial biogenesis and maintained fusion occurred in neurons along with mitochondrial fission following OGD; thus Mfn1 but not Drp1 may be a major regulator of these processes.
authors: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America. eawappler@gmail.com
authors: Edina A
authors: EA
authors: Wappler
authors: Adam
authors: A
authors: Institoris
authors: Somhrita
authors: S
authors: Dutta
authors: Prasad V G
authors: PV
authors: Katakam
authors: David W
authors: DW
authors: Busija
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000172:deficiency*; D063154:Mitochondrial Dynamics / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011247:Pregnancy; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D052999:Quinazolinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D024101:Mitochondrial Proteins; D052999:Quinazolinones; D050994:Voltage-Dependent Anion Channels; C037112:9-deoxy-delta-9-prostaglandin D2; D005947:Glucose; D015230:Prostaglandin D2; D010100:Oxygen
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