Motor Skill Learning Test

“24-month-old C57 BL/6 mice were treated with a cell-permeable, mitochondria-targeted antioxidant peptide (SS-31; 10 mg kg−1 day−1, i.p.) or vehicle for 2 weeks”

“CBF responses in the whisker barrel cortex elicited by contralateral whisker stimulation were significantly decreased in aged mice compared to young animals”

“Studies using an open cranial window preparation showed that in young animals administration of the NO synthase inhibitor L-NAME significantly decreased neurovascular coupling responses”

“Representative traces of cerebral blood flow (CBF; measured with a laser Doppler probe above the whisker barrel cortex) during contralateral whisker stimulation (30 s, 5 Hz)”

“In untreated aged animals, administration of L-NAME was without effect (Figure 2 a,b). In contrast, in SS-31-treated aged mice L-NAME significantly decreased CBF responses”

“endothelium-dependent vasodilator responses were tested in isolated, cannulated branches of the MCA. Pressurized MCAs developed spontaneous myogenic tone (~30%)”

“In young vessels, administration of acetylcholine (Figure 2 c) and ATP (Figure 2 d) resulted in significant dilation, whereas these responses were significantly attenuated in vessels derived from aging mice”

“In young vessels, administration of acetylcholine (Figure 2 c) and ATP (Figure 2 d) resulted in significant dilation”

“Vasodilator responses elicited by administration of the NO donor sodium nitroprusside (SNP) did not differ significantly among the experimental groups”

“we assessed the effects of SS-31 on cellular mtROS production in cultured CMVECs derived from aged animals using the MitoSox fluorescence method”

“SS-31 treatment elicited significant decreases in mtROS production in aged CMVECs, eliminating the difference between the two age groups (Figure 2 f). The antioxidative effects of SS-31 were manifested rapidly, with maximal reduction in mtROS being evident after 2 hr post-treatment”

“Attenuation of mtROS production in aged CMVECs was associated with significant improvement in mitochondrial respiration (Figure 2 g)”

“qPCR data showing cortical mRNA expression of nitric oxide synthases Nos3 and Nos1, arginases (Arg1, Arg2), NADPH oxidases (Nox1, Nox2), and superoxide dismutases (Sod1, Sod2)”