TY - JOUR
T1 - MiR-34a and stroke
T2 - Assessment of non-modifiable biological risk factors in cerebral ischemia
AU - Ren, Xuefang
AU - Engler-Chiurazzi, Elizabeth B.
AU - Russell, Ashley E.
AU - Sarkar, Saumyendra N.
AU - Rellick, Stephanie L.
AU - Lewis, Sara
AU - Corbin, Deborah
AU - Clapper, Jared
AU - Simpkins, James W.
N1 - Publisher Copyright:
© 2018
PY - 2019/7
Y1 - 2019/7
N2 - Aging of the nervous system, and the occurrence of age-related brain diseases such as stroke, are associated with changes to a variety of cellular processes controlled by many distinct genes. MicroRNAs (miRNAs), short non-coding functional RNAs that can induce translational repression or site-specific cleavage of numerous target mRNAs, have recently emerged as important regulators of cellular senescence, aging, and the response to neurological insult. Here, we focused on the assessment of the role of miR-34a in stroke. We noted increases in miR-34a expression in the blood of stroke patients as well as in blood and brain of mice subjected to experimental stroke. Our methodical genetic manipulation of miR-34a expression substantially impacted stroke-associated preclinical outcomes and we have in vitro evidence that these changes may be driven at least in part by disruptions to blood brain barrier integrity and mitochondrial oxidative phosphorylation in endothelial cells. Finally, aging, independent of brain injury, appears to be associated with shifts in circulating miRNA profiles. Taken together, these data support a role for miRNAs, and specifically miR-34a, in brain aging and the physiological response to age-related neurological insult, and lay the groundwork for future investigation of this novel therapeutic target.
AB - Aging of the nervous system, and the occurrence of age-related brain diseases such as stroke, are associated with changes to a variety of cellular processes controlled by many distinct genes. MicroRNAs (miRNAs), short non-coding functional RNAs that can induce translational repression or site-specific cleavage of numerous target mRNAs, have recently emerged as important regulators of cellular senescence, aging, and the response to neurological insult. Here, we focused on the assessment of the role of miR-34a in stroke. We noted increases in miR-34a expression in the blood of stroke patients as well as in blood and brain of mice subjected to experimental stroke. Our methodical genetic manipulation of miR-34a expression substantially impacted stroke-associated preclinical outcomes and we have in vitro evidence that these changes may be driven at least in part by disruptions to blood brain barrier integrity and mitochondrial oxidative phosphorylation in endothelial cells. Finally, aging, independent of brain injury, appears to be associated with shifts in circulating miRNA profiles. Taken together, these data support a role for miRNAs, and specifically miR-34a, in brain aging and the physiological response to age-related neurological insult, and lay the groundwork for future investigation of this novel therapeutic target.
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U2 - 10.1016/j.neuint.2018.10.019
DO - 10.1016/j.neuint.2018.10.019
M3 - Short survey
C2 - 30365981
AN - SCOPUS:85055746914
SN - 0197-0186
VL - 127
SP - 73
EP - 79
JO - Neurochemistry International
JF - Neurochemistry International
ER -