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Study · Animal study (in vivo) · mouse · 2018

7 results

Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice.

Tarantini S, Valcarcel-Ares NM, Yabluchanskiy A, Fulop GA, Hertelendy P, Gautam T, Farkas E, Perz A, Rabinovitch PS, Sonntag WE, Csiszar A, Ungvari Z

Aging cell6 Feb 2018Cited by 182 (Europe PMC)

Summary

Moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling has an essential role in maintenance of healthy cognitive function. In advanced age, increased oxidative stress and cerebromicrovascular endothelial dysfunction impair neurovascular coupling, likely contributing to age-related decline of higher cortical functions. There is increasing evidence showing that mitochondrial oxidative stress plays a critical role in a range of age-related cellular impairments, but its role in neurovascular uncoupling remains unexplored. This study was designed to test the hypothesis that attenuation of mitochondrial oxidative stress may exert beneficial effects on neurovascular coupling responses in aging. To test this hypothesis, 24-month-old C57BL/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. Neurovascular coupling was assessed by measuring CBF responses (laser speckle contrast imaging) evoked by contralateral whisker stimulation. We found that neurovascular coupling responses were significantly impaired in aged mice. Treatment with SS-31 significantly improved neurovascular coupling responses by increasing NO-mediated cerebromicrovascular dilation, which was associated with significantly improved spatial working memory, motor skill learning, and gait coordination. These findings are paralleled by the protective effects of SS-31 on mitochondrial production of reactive oxygen species and mitochondrial respiration in cultured cerebromicrovascular endothelial cells derived from aged animals. Thus, mitochondrial oxidative stress contributes to age-related cerebromicrovascular dysfunction, exacerbating cognitive decline. We propose that mitochondria-targeted antioxidants may be considered for pharmacological microvascular protection for the prevention/treatment of age-related vascular cognitive impairment (VCI).
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In aged mice, SS‑31 treatment significantly improved neurovascular coupling responses compared with vehicle.

    In plain wordsIn aged mice, SS‑31 improved the link between brain activity and blood flow compared with vehicle.

    Outcome
    IncreaseNeurovascular coupling response
    Study

    mousen: not reported in source

    Aged (24-month-old) C57BL/6 mice
    Comparator
    Vehicle
    Outcome group
    Cognition and memory · Nervous system and cognition
    Studied dose
    10 mg/kg/day · intraperitoneal · 2 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Treatment with SS-31 significantly improved neurovascular coupling responses by increasing NO-mediated cerebromicrovascular dilation
    2 context sentences
    Summary · context
    We found that neurovascular coupling responses were significantly impaired in aged mice.
    Summary · context
    To test this hypothesis, 24-month-old C57BL/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.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In aged mice, SS‑31 treatment increased NO-mediated cerebromicrovascular dilation.

    In plain wordsIn aged mice, SS‑31 increased nitric oxide-driven widening of small brain blood vessels.

    Outcome
    IncreaseNO-mediated cerebromicrovascular dilation
    Study

    mousen: not reported in source

    Aged (24-month-old) C57BL/6 mice
    Comparator
    Vehicle
    Outcome group
    Cognition and memory · Cardiovascular
    Studied dose
    10 mg/kg/day · intraperitoneal · 2 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Treatment with SS-31 significantly improved neurovascular coupling responses by increasing NO-mediated cerebromicrovascular dilation
    1 context sentence
    Summary · context
    To test this hypothesis, 24-month-old C57BL/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.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In aged mice, SS‑31 treatment was associated with significantly improved spatial working memory.

    In plain wordsIn aged mice, SS‑31 treatment was linked to better spatial working memory.

    Outcome
    IncreaseSpatial working memory
    Study

    mousen: not reported in source

    Aged (24-month-old) C57BL/6 mice
    Comparator
    Vehicle
    Outcome group
    Cognition and memory · Nervous system and cognition
    Studied dose
    10 mg/kg/day · intraperitoneal · 2 weeksAs given in this study (mouse).

    Source sentences

    Summary
    which was associated with significantly improved spatial working memory, motor skill learning, and gait coordination.
    1 context sentence
    Summary · context
    To test this hypothesis, 24-month-old C57BL/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.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In aged mice, SS‑31 treatment was associated with significantly improved motor skill learning.

    In plain wordsIn aged mice, SS‑31 treatment was linked to better motor skill learning.

    Outcome
    IncreaseMotor skill learning
    Study

    mousen: not reported in source

    Aged (24-month-old) C57BL/6 mice
    Comparator
    Vehicle
    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    10 mg/kg/day · intraperitoneal · 2 weeksAs given in this study (mouse).

    Source sentences

    Summary
    which was associated with significantly improved spatial working memory, motor skill learning, and gait coordination.
    1 context sentence
    Summary · context
    To test this hypothesis, 24-month-old C57BL/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.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In aged mice, SS‑31 treatment was associated with significantly improved gait coordination.

    In plain wordsIn aged mice, SS‑31 treatment was linked to better gait coordination.

    Outcome
    IncreaseGait coordination
    Study

    mousen: not reported in source

    Aged (24-month-old) C57BL/6 mice
    Comparator
    Vehicle
    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    10 mg/kg/day · intraperitoneal · 2 weeksAs given in this study (mouse).

    Source sentences

    Summary
    which was associated with significantly improved spatial working memory, motor skill learning, and gait coordination.
    1 context sentence
    Summary · context
    To test this hypothesis, 24-month-old C57BL/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.
  6. 06LabIn vitro (cells)Mechanism

    In cultured cerebromicrovascular endothelial cells from aged animals, SS‑31 had protective effects on mitochondrial production of reactive oxygen species.

    In plain wordsIn cells from aged mice, SS‑31 had a protective effect on the mitochondrial production of reactive oxygen species.

    Outcome
    DecreaseMitochondrial reactive oxygen species production in aged endothelial cells
    Study

    mousen: not reported in source

    Cultured cerebromicrovascular endothelial cells from aged animals
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    These findings are paralleled by the protective effects of SS-31 on mitochondrial production of reactive oxygen species and mitochondrial respiration in cultured cerebromicrovascular endothelial cells derived from aged animals.
  7. 07LabIn vitro (cells)Mechanism

    In cultured cerebromicrovascular endothelial cells from aged animals, SS‑31 had protective effects on mitochondrial respiration.

    In plain wordsIn cells from aged mice, SS‑31 had a protective effect on mitochondrial respiration.

    Outcome
    Direction not reportedMitochondrial respiration in aged endothelial cells
    Study

    mousen: not reported in source

    Cultured cerebromicrovascular endothelial cells from aged animals
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    These findings are paralleled by the protective effects of SS-31 on mitochondrial production of reactive oxygen species and mitochondrial respiration in cultured cerebromicrovascular endothelial cells derived from aged animals.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    9 Oct 2026, 18:17 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

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