Figure 3: Drp1-K38A restores synaptic release of DA in Pink1−/− mice.
From: Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo
Approximately 1-year-old Pink1−/− (KO) and Pink1+/+ (WT) littermates were transduced with eGFP-, Drp1-K38A- (a,b) or Fis1 (c,d)-expressing AAV2 vectors for 8 weeks before in vivo microdialysis was performed in freely moving mice. To evoke depolarization-induced release of DA, a total 240 nmol KCl in isotonic aCSF was delivered through the probe over a 15-min period (shaded box). Striatal dialysates were collected every 15 min and analysed simultaneously for DA and serotonin (e) levels using HPLC. Representative HPLC chromatograms of the 30-min fractions of a and c are shown in b and d, respectively. Areas under the curve of a and c were generated using GraphPad Prism and analysed by two-way analysis of variance (genotype × treatment: F2,17=8.63, P=0.003; n=3–5 mice per group), followed by Newman–Keuls post-hoc test. (a): *P<0.001 KO-GFP versus WT-GFP or versus KO-K38A. (c): *P<0.001 KO-GFP versus WT-GFP, #P=0.012 (WT-Fis1 versus WT-GFP) or #P=0.041 (WT-Fis1 versus KO-Fis1). (f) After microdialysis, brains were removed and processed for stereological cell counts of DA neurons, striatal terminal density and total striatal DA content.
