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Article ; Online: Effects of head-only or whole-body exposure to very low doses of

Rabin, Bernard M / Poulose, Shibu M / Bielinski, Donna F / Shukitt-Hale, Barbara

Life sciences in space research

2019 Volume 20, Page(s) 85–92

Abstract: On exploratory class missions, astronauts will be exposed to a range of heavy particles which vary in linear energy transfer (LET). Previous research has shown a direct relationship between particle LET and cognitive performance such that, as particle ... ...

Abstract	On exploratory class missions, astronauts will be exposed to a range of heavy particles which vary in linear energy transfer (LET). Previous research has shown a direct relationship between particle LET and cognitive performance such that, as particle LET decreases the dose needed to affect cognitive performance also decreases. Because a significant portion of the total dose experienced by astronauts may be expected to come from exposure to low LET
MeSH term(s)	Animals ; Behavior, Animal/radiation effects ; Cognition/physiology ; Cognition/radiation effects ; Head/radiation effects ; Helium/administration & dosage ; Male ; Neurons/physiology ; Neurons/radiation effects ; Rats ; Rats, Sprague-Dawley ; Whole-Body Irradiation/methods
Chemical Substances	Helium (206GF3GB41)
Language	English
Publishing date	2019-02-05
Publishing country	Netherlands
Document type	Journal Article
ISSN	2214-5532
ISSN (online)	2214-5532
DOI	10.1016/j.lssr.2019.02.001
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Article ; Online: Role of fruits, nuts, and vegetables in maintaining cognitive health.

Miller, Marshall G / Thangthaeng, Nopporn / Poulose, Shibu M / Shukitt-Hale, Barbara

Experimental gerontology

2017 Volume 94, Page(s) 24–28

Abstract: Population aging is leading to an increase in the incidence of age-related cognitive dysfunction and, with it, the health care burden of caring for older adults. Epidemiological studies have shown that consumption of fruits, nuts, and vegetables is ... ...

Abstract	Population aging is leading to an increase in the incidence of age-related cognitive dysfunction and, with it, the health care burden of caring for older adults. Epidemiological studies have shown that consumption of fruits, nuts, and vegetables is positively associated with cognitive ability; however, these foods, which contain a variety of neuroprotective phytochemicals, are widely under-consumed. Surprisingly few studies have investigated the effects of individual plant foods on cognitive health but recent clinical trials have shown that dietary supplementation with individual foods, or switching to a diet rich in several of these foods, can improve cognitive ability. While additional research is needed, increasing fruit, nut, and vegetable intake may be an effective strategy to prevent or delay the onset of cognitive dysfunction during aging.
Language	English
Publishing date	2017-08
Publishing country	England
Document type	Journal Article
ZDB-ID	390992-x
ISSN	1873-6815 ; 0531-5565
ISSN (online)	1873-6815
ISSN	0531-5565
DOI	10.1016/j.exger.2016.12.014
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Article ; Online: Walnut extract modulates activation of microglia through alteration in intracellular calcium concentration.

Thangthaeng, Nopporn / Poulose, Shibu M / Fisher, Derek R / Shukitt-Hale, Barbara

Nutrition research (New York, N.Y.)

2017 Volume 49, Page(s) 88–95

Abstract: Diets supplemented with walnuts have shown to protect brain against oxidative and inflammatory cytotoxicity and promote protective cellular and cognitive function. The current study was undertaken to test the hypothesize that whole walnut extract (WNE) ... ...

Abstract	Diets supplemented with walnuts have shown to protect brain against oxidative and inflammatory cytotoxicity and promote protective cellular and cognitive function. The current study was undertaken to test the hypothesize that whole walnut extract (WNE) inhibits lipopolysaccharide (LPS)-induced microglial activation by regulating calmodulin (CaM) expression through [Ca
MeSH term(s)	Animals ; Brain/cytology ; Brain/drug effects ; Brain/metabolism ; Calcium/metabolism ; Calcium-Binding Proteins/metabolism ; Calmodulin/metabolism ; Cell Line ; Enzyme Inhibitors/pharmacology ; Juglans ; Lipopolysaccharides ; Microfilament Proteins/metabolism ; Microglia/drug effects ; Microglia/metabolism ; Nitric Oxide Synthase Type II/metabolism ; Nuts ; Plant Extracts/pharmacology ; Potassium Chloride/pharmacology ; Rats ; Thapsigargin/pharmacology ; Up-Regulation
Chemical Substances	Aif1 protein, rat ; Calcium-Binding Proteins ; Calmodulin ; Enzyme Inhibitors ; Lipopolysaccharides ; Microfilament Proteins ; Plant Extracts ; Potassium Chloride (660YQ98I10) ; Thapsigargin (67526-95-8) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2017-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	582432-1
ISSN	1879-0739 ; 0271-5317
ISSN (online)	1879-0739
ISSN	0271-5317
DOI	10.1016/j.nutres.2017.10.016
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Article ; Online: Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function.

Poulose, Shibu M / Miller, Marshall G / Scott, Tammy / Shukitt-Hale, Barbara

Advances in nutrition (Bethesda, Md.)

2017 Volume 8, Issue 6, Page(s) 804–811

Abstract: Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. ... ...

Abstract	Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural plasticity, brain homeostasis, and maintenance in the central nervous system and is a crucial factor in preserving the cognitive function and repair of damaged brain cells affected by aging and brain disorders. Intrinsic factors such as aging, neuroinflammation, oxidative stress, and brain injury, as well as lifestyle factors such as high-fat and high-sugar diets and alcohol and opioid addiction, negatively affect adult neurogenesis. Conversely, many dietary components such as curcumin, resveratrol, blueberry polyphenols, sulforaphane, salvionic acid, polyunsaturated fatty acids (PUFAs), and diets enriched with polyphenols and PUFAs, as well as caloric restriction, physical exercise, and learning, have been shown to induce neurogenesis in adult brains. Although many of the underlying mechanisms by which nutrients and dietary factors affect adult neurogenesis have yet to be determined, nutritional approaches provide promising prospects to stimulate adult neurogenesis and combat neurodegenerative diseases and cognitive decline. In this review, we summarize the evidence supporting the role of nutritional factors in modifying adult neurogenesis and their potential to preserve cognitive function during aging.
MeSH term(s)	Adult ; Aged ; Aging/physiology ; Brain/physiology ; Cognition/physiology ; Cognitive Dysfunction/physiopathology ; Female ; Hippocampus/physiology ; Humans ; Male ; Middle Aged ; Neurodegenerative Diseases/physiopathology ; Neurogenesis/physiology ; Nutritional Physiological Phenomena/physiology
Language	English
Publishing date	2017-11-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2583634-1
ISSN	2156-5376 ; 2156-5376
ISSN (online)	2156-5376
ISSN	2156-5376
DOI	10.3945/an.117.016261
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Article: Walnut extract modulates activation of microglia through alteration in intracellular calcium concentration

Thangthaeng, Nopporn / Fisher, Derek R / Poulose, Shibu M / Shukitt-Hale, Barbara

Nutrition research. 2018 Jan., v. 49

2018

Abstract	Diets supplemented with walnuts have shown to protect brain against oxidative and inflammatory cytotoxicity and promote protective cellular and cognitive function. The current study was undertaken to test the hypothesize that whole walnut extract (WNE) inhibits lipopolysaccharide (LPS)-induced microglial activation by regulating calmodulin (CaM) expression through [Ca2+]i. To test this hypothesis, we used an in vitro model the highly aggressively proliferating immortalized cells, a rat microglial cell line, treated with various concentrations of WNEs. Treatment with WNE (1.5%, 3%, or 6%) induced a slow rise in intracellular calcium in a concentration- and time-dependent manner, and this rise became exaggerated when cells were depolarized with potassium chloride (100 mmol/L). Cells treated with WNE (1%, 3%, or 6%) upregulated CaM protein levels, with 1 hour posttreatment being the peak time, regardless of WNE concentration. Interestingly, this WNE-induced upregulation of CaM was blocked by pretreatment with thapsigargin. Additionally, treatment with WNE (1%, 3%, or 6%) 1 hour prior to LPS treatment was found to be effective in preventing LPS-induced upregulation of inducible nitric oxide synthase expression, upregulation of ionized Ca2+-binding adaptor-1, and downregulation of CaM. These findings suggest that bioactive compounds in walnut are capable of modulating microglial activation through regulation of intracellular calcium and CaM expression. Nutritional interventions using walnuts may be effective in the amelioration of chronic inflammation and neurodegeneration.
Keywords	bioactive compounds ; brain ; calcium ; calmodulin ; cell lines ; cognition ; cytotoxicity ; dietary supplements ; inducible nitric oxide synthase ; inflammation ; ionization ; lipopolysaccharides ; models ; neurodegenerative diseases ; neuroglia ; nutritional intervention ; potassium chloride ; protein content ; rats ; walnuts
Language	English
Dates of publication	2018-01
Size	p. 88-95.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	582432-1
ISSN	1879-0739 ; 0271-5317
ISSN (online)	1879-0739
ISSN	0271-5317
DOI	10.1016/j.nutres.2017.10.016
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Article ; Online: Preserving Brain Function in Aging: The Anti-glycative Potential of Berry Fruit.

Thangthaeng, Nopporn / Poulose, Shibu M / Miller, Marshall G / Shukitt-Hale, Barbara

Neuromolecular medicine

2016 Volume 18, Issue 3, Page(s) 465–473

Abstract: Advanced glycation end products (AGEs) are naturally occurring macromolecules that are formed in vivo by the non-enzymatic modification of proteins, lipids, or nucleic acids by sugar, even in the absence of hyperglycemia. In the diet, AGEs are found in ... ...

Abstract	Advanced glycation end products (AGEs) are naturally occurring macromolecules that are formed in vivo by the non-enzymatic modification of proteins, lipids, or nucleic acids by sugar, even in the absence of hyperglycemia. In the diet, AGEs are found in animal products, and additional AGEs are produced when those foods are cooked at high temperatures. Studies have linked AGEs to various age-related physiological changes, including wrinkles, diabetic complications, and neurodegenerative disease, including Alzheimer's disease. Dietary berry fruits have been shown to reduce the severity or slow the progression of many physiological changes and disease pathologies that accompany aging. Emerging evidence has shown that the phytochemicals found in berry fruits exhibit anti-glycative activity. In this review, we briefly summarize the current evidence supporting the neuroprotective anti-glycative activity of berry fruits and their potential to preserve cognitive function during aging.
Language	English
Publishing date	2016-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2077809-0
ISSN	1559-1174 ; 1535-1084
ISSN (online)	1559-1174
ISSN	1535-1084
DOI	10.1007/s12017-016-8400-3
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Zs.A 5818: Show issues

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Article ; Online: Role of walnuts in maintaining brain health with age.

Poulose, Shibu M / Miller, Marshall G / Shukitt-Hale, Barbara

The Journal of nutrition

2014 Volume 144, Issue 4 Suppl, Page(s) 561S–566S

Abstract: Because of the combination of population growth and population aging, increases in the incidence of chronic neurodegenerative disorders have become a societal concern, both in terms of decreased quality of life and increased financial burden. Clinical ... ...

Abstract	Because of the combination of population growth and population aging, increases in the incidence of chronic neurodegenerative disorders have become a societal concern, both in terms of decreased quality of life and increased financial burden. Clinical manifestation of many of these disorders takes years, with the initiation of mild cognitive symptoms leading to behavioral problems, dementia and loss of motor functions, the need for assisted living, and eventual death. Lifestyle factors greatly affect the progression of cognitive decline, with high-risk behaviors including unhealthy diet, lack of exercise, smoking, and exposure to environmental toxins leading to enhanced oxidative stress and inflammation. Although there exists an urgent need to develop effective treatments for age-related cognitive decline and neurodegenerative disease, prevention strategies have been underdeveloped. Primary prevention in many of these neurodegenerative diseases could be achieved earlier in life by consuming a healthy diet, rich in antioxidant and anti-inflammatory phytochemicals, which offers one of the most effective and least expensive ways to address the crisis. English walnuts (Juglans regia L.) are rich in numerous phytochemicals, including high amounts of polyunsaturated fatty acids, and offer potential benefits to brain health. Polyphenolic compounds found in walnuts not only reduce the oxidant and inflammatory load on brain cells but also improve interneuronal signaling, increase neurogenesis, and enhance sequestration of insoluble toxic protein aggregates. Evidence for the beneficial effects of consuming a walnut-rich diet is reviewed in this article.
MeSH term(s)	Aged ; Aging ; Brain/physiology ; Brain Diseases/diet therapy ; Brain Diseases/metabolism ; Brain Diseases/prevention & control ; Humans ; Juglans ; Neurodegenerative Diseases/diet therapy ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/prevention & control
Language	English
Publishing date	2014-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.3945/jn.113.184838
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Article: Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function

Poulose, Shibu M / Miller, Marshall G / Scott, Tammy / Shukitt-Hale, Barbara

Advances in nutrition. 2017 Nov. 07, v. 8, no. 6

2017

Abstract	Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural plasticity, brain homeostasis, and maintenance in the central nervous system and is a crucial factor in preserving the cognitive function and repair of damaged brain cells affected by aging and brain disorders. Intrinsic factors such as aging, neuroinflammation, oxidative stress, and brain injury, as well as lifestyle factors such as high-fat and high-sugar diets and alcohol and opioid addiction, negatively affect adult neurogenesis. Conversely, many dietary components such as curcumin, resveratrol, blueberry polyphenols, sulforaphane, salvionic acid, polyunsaturated fatty acids (PUFAs), and diets enriched with polyphenols and PUFAs, as well as caloric restriction, physical exercise, and learning, have been shown to induce neurogenesis in adult brains. Although many of the underlying mechanisms by which nutrients and dietary factors affect adult neurogenesis have yet to be determined, nutritional approaches provide promising prospects to stimulate adult neurogenesis and combat neurodegenerative diseases and cognitive decline. In this review, we summarize the evidence supporting the role of nutritional factors in modifying adult neurogenesis and their potential to preserve cognitive function during aging.
Keywords	adults ; blueberries ; brain ; brain damage ; cognition ; cognitive disorders ; curcumin ; exercise ; high carbohydrate diet ; homeostasis ; intrinsic factors ; learning ; lifestyle ; low calorie diet ; neurodegenerative diseases ; neurogenesis ; neurons ; nutrients ; oxidative stress ; plasticity ; polyphenols ; polyunsaturated fatty acids ; resveratrol ; stem cells ; sulforaphane
Language	English
Dates of publication	2017-1107
Size	p. 804-811.
Publishing place	Oxford University Press
Document type	Article
ZDB-ID	2583634-1
ISSN	2156-5376 ; 2161-8313
ISSN (online)	2156-5376
ISSN	2161-8313
DOI	10.3945/an.117.016261
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Article ; Online: Blueberries Improve Neuroinflammation and Cognition differentially Depending on Individual Cognitive baseline Status.

Shukitt-Hale, Barbara / Thangthaeng, Nopporn / Miller, Marshall G / Poulose, Shibu M / Carey, Amanda N / Fisher, Derek R

The journals of gerontology. Series A, Biological sciences and medical sciences

2019 Volume 74, Issue 7, Page(s) 977–983

Abstract: Daily supplementation of blueberries (BBs) reverses age-related deficits in behavior in aged rats. However, it is unknown whether BB is more beneficial to one subset of the population dependent on baseline cognitive performance and inflammatory status. ... ...

Abstract	Daily supplementation of blueberries (BBs) reverses age-related deficits in behavior in aged rats. However, it is unknown whether BB is more beneficial to one subset of the population dependent on baseline cognitive performance and inflammatory status. To examine the effect of individual differences on the efficacy of BB, aged rats (17 months old) were assessed for cognition in the radial arm water maze (RAWM) and divided into good, average, and poor performers based on navigation errors. Half of the rats in each cognitive group were then fed a control or a 2% BB diet for 8 weeks before retesting. Serum samples were collected, pre-diet and post-diet, to assess inflammation. Latency in the radial arm water maze was significantly reduced in the BB-fed poor performers (p < .05) and preserved in the BB-fed good performers. The control-fed good performers committed more working and reference memory errors in the post-test than pretest (p < .05), whereas the BB-fed good performers showed no change. An in vitro study using the serum showed that BB supplementation attenuated lipopolysaccharide (LPS)-induced nitrite and tumor necrosis factor-alpha, and cognitive performance was associated with innate anti-inflammatory capability. Therefore, consumption of BB may reverse some age-related deficits in cognition, as well as preserve function among those with intact cognitive ability.
MeSH term(s)	Aging/immunology ; Aging/psychology ; Animals ; Anti-Inflammatory Agents/immunology ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/metabolism ; Antioxidants/pharmacology ; Behavior, Animal ; Blueberry Plants ; Cognition/drug effects ; Cognition/physiology ; Diet Therapy/methods ; Maze Learning ; Neuroimmunomodulation/drug effects ; Neuroimmunomodulation/physiology ; Plants, Medicinal ; Rats ; Treatment Outcome ; Tumor Necrosis Factor-alpha/blood
Chemical Substances	Anti-Inflammatory Agents ; Antioxidants ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2019-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glz048
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Article ; Online: Walnut diet reduces accumulation of polyubiquitinated proteins and inflammation in the brain of aged rats.

Poulose, Shibu M / Bielinski, Donna F / Shukitt-Hale, Barbara

The Journal of nutritional biochemistry

2013 Volume 24, Issue 5, Page(s) 912–919

Abstract: An increase in the aggregation of misfolded/damaged polyubiquitinated proteins has been the hallmark of many age-related neurodegenerative diseases. The accumulation of these potentially toxic proteins in brain increases with age, in part due to ... ...

Abstract	An increase in the aggregation of misfolded/damaged polyubiquitinated proteins has been the hallmark of many age-related neurodegenerative diseases. The accumulation of these potentially toxic proteins in brain increases with age, in part due to increased oxidative and inflammatory stresses. Walnuts, rich in omega fatty acids, have been shown to improve memory, cognition and neuronal effects related to oxidative stress (OS) and inflammation (INF) in animals and human trials. The current study found that feeding 19-month-old rats with a 6% or 9% walnut diet significantly reduced the aggregation of polyubiquitinated proteins and activated autophagy, a neuronal housekeeping function, in the striatum and hippocampus. Walnut-fed animals exhibited up-regulation of autophagy through inhibiting phosphorylation of mTOR, up-regulating ATG7 and Beclin 1, and turnover of MAP1BLC3 proteins. The clearance of polyubiquitinated protein aggregates such as p62/SQSTM1 was more profound in hippocampus, a critical region in the brain involved in memory and cognitive performance, than striatum. The clearance of ubiquitinated aggregates was in tandem with significant reductions in OS/INF, as indicated by the levels of P38-MAP kinase and phosphorylations of nuclear factor kappa B and cyclic AMP response element binding protein. The results demonstrate the effectiveness of a walnut-supplemented diet in activating the autophagy function in brain beyond its traditionally known antioxidant and anti-inflammatory benefits.
MeSH term(s)	Animals ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/metabolism ; Autophagy/drug effects ; Autophagy-Related Protein 7 ; Beclin-1 ; Brain/drug effects ; Brain/metabolism ; Cognition/drug effects ; Cyclic AMP Response Element-Binding Protein/genetics ; Cyclic AMP Response Element-Binding Protein/metabolism ; Diet ; Fatty Acids, Unsaturated/administration & dosage ; Hippocampus/drug effects ; Hippocampus/metabolism ; Inflammation/prevention & control ; Juglans ; Male ; Memory/drug effects ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Nuts ; Oxidative Stress/drug effects ; Phosphorylation/drug effects ; Rats ; Rats, Inbred F344 ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Ubiquitin-Activating Enzymes/genetics ; Ubiquitin-Activating Enzymes/metabolism ; Ubiquitinated Proteins/genetics ; Ubiquitinated Proteins/metabolism ; Up-Regulation ; p38 Mitogen-Activated Protein Kinases/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemical Substances	Apoptosis Regulatory Proteins ; Atg7 protein, rat ; Beclin-1 ; Becn1 protein, rat ; Cyclic AMP Response Element-Binding Protein ; Fatty Acids, Unsaturated ; NF-kappa B ; Ubiquitinated Proteins ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; mTOR protein, rat (EC 2.7.1.1) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Autophagy-Related Protein 7 (EC 6.2.1.45) ; Ubiquitin-Activating Enzymes (EC 6.2.1.45)
Language	English
Publishing date	2013-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2012.06.009
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