Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging

Jonathan A. Zweig; Mikah S. Brandes; Barbara H. Brumbach; Maya Caruso; Kirsten M. Wright; Joseph F. Quinn; Amala Soumyanath; Nora E. Gray

doi:10.1016/j.neurobiolaging.2020.11.019

Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging

Jonathan A. Zweig, Mikah S. Brandes, Barbara H. Brumbach, Maya Caruso, Kirsten M. Wright, Joseph F. Quinn, Amala Soumyanath, Nora E. Gray

Neurology

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16 Scopus citations

Abstract

The water extract of Centella asiatica (CAW) improves cognitive and mitochondrial function and activates the nuclear factor erythroid 2-related factor 2 (NRF2) regulated antioxidant response pathway in aged mice. Here we investigate whether NRF2 activation is required for the cognitive and mitochondrial effects of prolonged CAW exposure during aging. Five-month-old NRF2 knockout (NRF2KO) and wild-type mice were treated with CAW for 1, 7, or 13 months. Each cohort underwent cognitive testing and hippocampal mitochondrial analyses. Age-related cognitive decline was accelerated in NRF2KO mice and while CAW treatment improved cognitive performance in wild-type mice, it had no effect on NRF2KO animals. Hippocampal mitochondrial function also declined further with age in NRF2KO mice and greater hippocampal mitochondrial dysfunction was associated with poorer cognitive performance in both genotypes. Long-term CAW treatment did not affect mitochondrial endpoints in animals of either genotype. These data indicate that loss of NRF2 results in accelerated age-related cognitive decline and worsened mitochondrial deficits. NRF2 also appears to be required for the cognitive enhancing effects of CAW during aging.

Original language	English (US)
Pages (from-to)	48-58
Number of pages	11
Journal	Neurobiology of Aging
Volume	100
DOIs	https://doi.org/10.1016/j.neurobiolaging.2020.11.019
State	Published - Apr 2021

Keywords

Aging
Cognitive impairment
Mitochondrial dysfunction

ASJC Scopus subject areas

General Neuroscience
Aging
Developmental Biology
Clinical Neurology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2020.11.019

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Zweig, J. A., Brandes, M. S., Brumbach, B. H., Caruso, M., Wright, K. M., Quinn, J. F., Soumyanath, A., & Gray, N. E. (2021). Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging. Neurobiology of Aging, 100, 48-58. https://doi.org/10.1016/j.neurobiolaging.2020.11.019

Zweig, JA, Brandes, MS, Brumbach, BH, Caruso, M, Wright, KM , Quinn, JF , Soumyanath, A & Gray, NE 2021, 'Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging', Neurobiology of Aging, vol. 100, pp. 48-58. https://doi.org/10.1016/j.neurobiolaging.2020.11.019

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title = "Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging",

abstract = "The water extract of Centella asiatica (CAW) improves cognitive and mitochondrial function and activates the nuclear factor erythroid 2-related factor 2 (NRF2) regulated antioxidant response pathway in aged mice. Here we investigate whether NRF2 activation is required for the cognitive and mitochondrial effects of prolonged CAW exposure during aging. Five-month-old NRF2 knockout (NRF2KO) and wild-type mice were treated with CAW for 1, 7, or 13 months. Each cohort underwent cognitive testing and hippocampal mitochondrial analyses. Age-related cognitive decline was accelerated in NRF2KO mice and while CAW treatment improved cognitive performance in wild-type mice, it had no effect on NRF2KO animals. Hippocampal mitochondrial function also declined further with age in NRF2KO mice and greater hippocampal mitochondrial dysfunction was associated with poorer cognitive performance in both genotypes. Long-term CAW treatment did not affect mitochondrial endpoints in animals of either genotype. These data indicate that loss of NRF2 results in accelerated age-related cognitive decline and worsened mitochondrial deficits. NRF2 also appears to be required for the cognitive enhancing effects of CAW during aging.",

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author = "Zweig, {Jonathan A.} and Brandes, {Mikah S.} and Brumbach, {Barbara H.} and Maya Caruso and Wright, {Kirsten M.} and Quinn, {Joseph F.} and Amala Soumyanath and Gray, {Nora E.}",

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doi = "10.1016/j.neurobiolaging.2020.11.019",

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AU - Zweig, Jonathan A.

AU - Brandes, Mikah S.

AU - Brumbach, Barbara H.

AU - Caruso, Maya

AU - Wright, Kirsten M.

AU - Quinn, Joseph F.

AU - Soumyanath, Amala

AU - Gray, Nora E.

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N2 - The water extract of Centella asiatica (CAW) improves cognitive and mitochondrial function and activates the nuclear factor erythroid 2-related factor 2 (NRF2) regulated antioxidant response pathway in aged mice. Here we investigate whether NRF2 activation is required for the cognitive and mitochondrial effects of prolonged CAW exposure during aging. Five-month-old NRF2 knockout (NRF2KO) and wild-type mice were treated with CAW for 1, 7, or 13 months. Each cohort underwent cognitive testing and hippocampal mitochondrial analyses. Age-related cognitive decline was accelerated in NRF2KO mice and while CAW treatment improved cognitive performance in wild-type mice, it had no effect on NRF2KO animals. Hippocampal mitochondrial function also declined further with age in NRF2KO mice and greater hippocampal mitochondrial dysfunction was associated with poorer cognitive performance in both genotypes. Long-term CAW treatment did not affect mitochondrial endpoints in animals of either genotype. These data indicate that loss of NRF2 results in accelerated age-related cognitive decline and worsened mitochondrial deficits. NRF2 also appears to be required for the cognitive enhancing effects of CAW during aging.

AB - The water extract of Centella asiatica (CAW) improves cognitive and mitochondrial function and activates the nuclear factor erythroid 2-related factor 2 (NRF2) regulated antioxidant response pathway in aged mice. Here we investigate whether NRF2 activation is required for the cognitive and mitochondrial effects of prolonged CAW exposure during aging. Five-month-old NRF2 knockout (NRF2KO) and wild-type mice were treated with CAW for 1, 7, or 13 months. Each cohort underwent cognitive testing and hippocampal mitochondrial analyses. Age-related cognitive decline was accelerated in NRF2KO mice and while CAW treatment improved cognitive performance in wild-type mice, it had no effect on NRF2KO animals. Hippocampal mitochondrial function also declined further with age in NRF2KO mice and greater hippocampal mitochondrial dysfunction was associated with poorer cognitive performance in both genotypes. Long-term CAW treatment did not affect mitochondrial endpoints in animals of either genotype. These data indicate that loss of NRF2 results in accelerated age-related cognitive decline and worsened mitochondrial deficits. NRF2 also appears to be required for the cognitive enhancing effects of CAW during aging.

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KW - Mitochondrial dysfunction

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Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging

Abstract

Keywords

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