D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease
J. Clin. Invest. Kim Tieu, et al. 112:892 doi:10.1172/JCI18797 [
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Figure 2Protective effect of DβHB against MPTP-induced neurodegeneration. (
a–
h) TH-positive neurons in SNpc, and (
i–
p) TH-positive terminals in striatum. Animals were infused subcutaneously with vehicle (saline;
a,
e,
i, and
m), DβHB (1.6 mmol/kg/d;
b,
d,
f,
h,
j,
l,
n, and
p), or LβHB (1.6 mmol/kg/d;
c,
g,
k, and
o) 1 day before receiving intraperitoneal injections of either saline (
a–
d and
i–
l) or MPTP (18 mg/kg;
e–
h and
m–
p). There is an extensive loss of TH-positive neurons (
e) and terminals (
m) in MPTP-injected animals. This loss is attenuated by DβHB (
f and
n) but not by its inactive isomer LβHB (
g and
o). The complex II inhibitor 3-NP was given intraperitoneally (15 mg/kg) daily for the entire period of DβHB infusion. In the presence of 3-NP, DβHB does not confer neuroprotection. Scale bars: 500 μm (
a–
h) and 1 mm (
i–
p). Please refer to Table
1 for quantification of neurons and terminals in each animal group.
