scholarly journals Adropin expression correlates with age-related neuropathologies in the human brain and improves neuroinflammation and cognitive function in aging mice

2021 ◽  
Author(s):  
Subhashis Banerjee ◽  
Sarbani Ghoshal ◽  
Clemence Girardet ◽  
Kelly M. DeMars ◽  
Changjun Yang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Human Brain ◽  
Stress Responses ◽  
Gene Clusters ◽  
Mitochondrial Metabolism ◽  
Protein Markers ◽  
Human Brain Tissue ◽  
Markers Of Inflammation ◽  
Age Related ◽  
Old Mice

Abstract Adropin is most abundant in neural tissues yet its neurological functions are unclear. Data from post-mortem human brain tissue samples indicates adropin expression occurs predominantly in astrocytes, peaks during critical post-natal periods of brain development, and then declines with aging. Previous experiments indicate adropin regulates mitochondrial metabolism. Gene clusters correlating with adropin are age- and dementia-specific, possibly indicating survivor bias. In people aged <40y adropin correlates positively with genes involved in mitochondrial metabolism, APOE and Clusterin. In the ‘old-old’ (>75y) with dementia, adropin expression correlates with genes linked to mitochondrial metabolism and neurodegenerative conditions. In the ‘old-old’ (>75y) without dementia, adropin correlates with genes involved in morphogenesis, growth of neuronal processes (dendrites, axons) and synapse function. Accordingly, adropin elicits neurotrophic responses in primary cultured neurons. Adropin expression also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in people without dementia, indicating a link to cellular stressors. How variation in brain adropin expression affects neurological aging was investigated using C57BL/6J mice. In mice, adropin is more widely expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia. Preventing the decline in expression observed with aging of mice using transgenesis improved cognitive function and resilience, while also reducing mRNA markers of inflammation in 18-month old mice. Treating 18-month old mice with adropin peptide also improved cognitive performance. These results link adropin expression to cellular energy metabolism and stress responses in the brain and indicates a possible relationship with aging-related cognitive decline.

Association between circulating inflammatory markers and marksmanship following intense military training

2018 ◽  
Vol 165 (6) ◽  
pp. 391-394
Author(s):  
Yftach Gepner ◽  
J R Hoffman ◽  
M W Hoffman ◽  
H Zelicha ◽  
H Cohen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Test Performance ◽  
Military Training ◽  
Protein Markers ◽  
Military Operations ◽  
Field Training ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Combat Unit ◽  
Factor Α

IntroductionIntense military operations during deployment or training are associated with elevations in inflammatory cytokine markers. However, the influence of an inflammatory response on military-specific skills is unclear. This study examined the association between brain-derived neurotrophic factor (BDNF), glial fibrillar acidic protein, markers of inflammation, marksmanship and cognitive function following a week of intense military field training.MethodsTwenty male soldiers (20.1±0.6 years; 1.78±0.05m; 74.1±7.9kg) from the same elite combat unit of the Israel Defense Forces volunteered to participate in this study. Soldiers completed a five-day period of intense field training including navigation of 27.8km/day with load carriages of ~50% of their body mass. Soldiers slept approximately fivehours per day and were provided with military field rations. Following the final navigational exercise, soldiers returned to their base and provided a blood sample. In addition, cognitive function assessment and both dynamic and static shooting (15 shots each) were performed following a 200 m gauntlet, in which soldiers had to use hand-to-hand combat skills to reach the shooting range.ResultsResults revealed that tumour necrosis factor-α (TNF-α) concentrations were inversely correlated with dynamic shooting (r=−0.646, p=0.005). In addition, a trend (r=0.415, p=0.098) was noted between TNF-α concentrations and target engagement speed (ie, time to complete the shooting protocol). BDNF concentrations were significantly correlated with the Serial Sevens Test performance (r=0.672, p=0.012).ConclusionThe results of this investigation indicate that elevated TNF-α concentrations and lower BDNF concentrations in soldiers following intense military training were associated with decreases in marksmanship and cognitive function, respectively.

scholarly journals Alkali metals levels in the human brain tissue: Anatomical region differences and age-related changes

2016 ◽  
Vol 38 ◽  
pp. 174-182 ◽  
Author(s):  
Patrícia Ramos ◽  
Agostinho Santos ◽  
Edgar Pinto ◽  
Nair Rosas Pinto ◽  
Ricardo Mendes ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Alkali Metals ◽  
Human Brain Tissue ◽  
Anatomical Region ◽  
Age Related ◽  
Age Related Changes

scholarly journals Tau Contributes to Sevoflurane-induced Neurocognitive Impairment in Neonatal Mice

2020 ◽  
Vol 133 (3) ◽  
pp. 595-610 ◽  
Author(s):  
Yang Yu ◽  
Yongyan Yang ◽  
Hong Tan ◽  
Myriam Boukhali ◽  
Ashok Khatri ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Tau Phosphorylation ◽  
Mitochondrial Metabolism ◽  
Sevoflurane Anesthesia ◽  
Neonatal Mice ◽  
Adult Mice ◽  
Baseline Conditions ◽  
Old Mice

Background Sevoflurane anesthesia induces Tau phosphorylation and cognitive impairment in neonatal but not in adult mice. This study tested the hypothesis that differences in brain Tau amounts and in the activity of mitochondria–adenosine triphosphate (ATP)–Nuak1–Tau cascade between the neonatal and adult mice contribute to the age-dependent effects of sevoflurane on cognitive function. Methods 6- and 60-day-old mice of both sexes received anesthesia with 3% sevoflurane for 2 h daily for 3 days. Biochemical methods were used to measure amounts of Tau, phosphorylated Tau, Nuak1, ATP concentrations, and mitochondrial metabolism in the cerebral cortex and hippocampus. The Morris water maze test was used to evaluate cognitive function in the neonatal and adult mice. Results Under baseline conditions and compared with 60-day-old mice, 6-day-old mice had higher amounts of Tau (2.6 ± 0.4 [arbitrary units, mean ± SD] vs. 1.3 ± 0.2; P &lt; 0.001), Tau oligomer (0.3 ± 0.1 vs. 0.1 ± 0.1; P = 0.008), and Nuak1 (0.9 ± 0.3 vs. 0.3 ± 0.1; P = 0.025) but lesser amounts of ATP (0.8 ± 0.1 vs. 1.5 ± 0.1; P &lt; 0.001) and mitochondrial metabolism (74.8 ± 14.1 [pmol/min] vs. 169.6 ± 15.3; P &lt; 0.001) in the cerebral cortex. Compared with baseline conditions, sevoflurane anesthesia induced Tau phosphorylation at its serine 202/threonine 205 residues (1.1 ± 0.4 vs. 0.2 ± 0.1; P &lt; 0.001) in the 6-day-old mice but not in the 60-day-old mice (0.05 ± 0.04 vs. 0.03 ± 0.01; P = 0.186). The sevoflurane-induced Tau phosphorylation and cognitive impairment in the neonatal mice were both attenuated by the inhibition of Nuak1 and the treatment of vitamin K2. Conclusions Higher brain Tau concentrations and lower brain mitochondrial metabolism in neonatal compared with adult mice contribute to developmental stage–dependent cognitive dysfunction after sevoflurane anesthesia. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

scholarly journals Aging Does Not Exacerbate Muscle Loss During Denervation and Lends Unique Muscle-Specific Atrophy Resistance With Akt Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jae-Sung You ◽  
Jie Chen
Keyword(s):  
Muscle Atrophy ◽  
Stress Responses ◽  
Mammalian Target Of Rapamycin ◽  
Akt Signaling ◽  
Skeletal Muscle Atrophy ◽  
Muscle Loss ◽  
Akt Activation ◽  
Age Related ◽  
Age Dependent ◽  
Old Mice

Sarcopenia, or age-related skeletal muscle atrophy and weakness, imposes significant clinical and economic burdens on affected patients and societies. Neurological degeneration, such as motoneuron death, has been recognized as a key contributor to sarcopenia. However, little is known about how aged/sarcopenic muscle adapts to this denervation stress. Here, we show that mice at 27months of age exhibit clear signs of sarcopenia but no accelerated denervation-induced muscle atrophy when compared to 8-month-old mice. Surprisingly, aging lends unique atrophy resistance to tibialis anteria muscle, accompanied by an increase in the cascade of mammalian target of rapamycin complex 1 (mTORC1)-independent anabolic events involving Akt signaling, rRNA biogenesis, and protein synthesis during denervation. These results expand our understanding of age-dependent stress responses and may help develop better countermeasures to sarcopenia.

scholarly journals Neuropathology of SUDEP

Neurology ◽  
2017 ◽  
Vol 88 (6) ◽  
pp. 551-561 ◽  
Author(s):  
Zuzanna Michalak ◽  
Dima Obari ◽  
Matthew Ellis ◽  
Maria Thom ◽  
Sanjay M. Sisodiya
Keyword(s):  
Human Brain ◽  
Hypoxia Inducible Factor ◽  
Human Leukocyte ◽  
Immunohistochemical Analysis ◽  
Brain Regions ◽  
Glial Fibrillary Acid Protein ◽  
Human Brain Tissue ◽  
Unexpected Death ◽  
Markers Of Inflammation ◽  
Starting Point

Objective:To seek a neuropathologic signature of sudden unexpected death in epilepsy (SUDEP) in a postmortem cohort by use of immunohistochemistry for specific markers of inflammation, gliosis, acute neuronal injury due to hypoxia, and blood-brain barrier (BBB) disruption, enabling the generation of hypotheses about potential mechanisms of death in SUDEP.Methods:Using immunohistochemistry, we investigated the expression of 6 markers (CD163, human leukocyte antigen–antigen D related, glial fibrillary acid protein, hypoxia-inducible factor-1α [HIF-1α], immunoglobulin G, and albumin) in the hippocampus, amygdala, and medulla in 58 postmortem cases: 28 SUDEP (definite and probable), 12 epilepsy controls, and 18 nonepileptic sudden death controls. A semiquantitative measure of immunoreactivity was scored for all markers used, and quantitative image analysis was carried out for selected markers.Results:Immunoreactivity was observed for all markers used within all studied brain regions and groups. Immunoreactivity for inflammatory reaction, BBB leakage, and HIF-1α in SUDEP cases was not different from that seen in control groups.Conclusions:This study represents a starting point to explore by immunohistochemistry the mechanisms underlying SUDEP in human brain tissue. Our approach highlights the potential and importance of considering immunohistochemical analysis to help identify biomarkers of SUDEP. Our results suggest that with the markers used, there is no clear immunohistochemical signature of SUDEP in human brain.

scholarly journals Adropin correlates with aging-related neuropathology in humans and improves cognitive function in aging mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Subhashis Banerjee ◽  
Sarbani Ghoshal ◽  
Clemence Girardet ◽  
Kelly M. DeMars ◽  
Changjun Yang ◽  
...  
Keyword(s):  
Cellular Metabolism ◽  
Enrichment Analysis ◽  
Spatial Learning And Memory ◽  
Oligodendrocyte Progenitor Cells ◽  
Protein Markers ◽  
Markers Of Inflammation ◽  
Expression Of Genes ◽  
Age Related ◽  
And Function ◽  
Mrna Markers

AbstractThe neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is highly expressed in astrocytes and peaks during critical postnatal periods of brain development. Gene enrichment analysis of transcripts correlating with adropin expression suggests processes relevant to aging-related neurodegenerative diseases that vary with age and dementia state, possibly indicating survivor bias. In people aged <40 y and ‘old-old’ (>75 y) diagnosed with dementia, adropin correlates positively with genes involved in mitochondrial processes. In the ‘old-old’ without dementia adropin expression correlates positively with morphogenesis and synapse function. Potent neurotrophic responses in primary cultured neurons are consistent with adropin supporting the development and function of neural networks. Adropin expression in the ‘old-old’ also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in those without dementia. How variation in brain adropin expression affects neurological aging was investigated using old (18-month) C57BL/6J mice. In mice adropin is expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia and shows correlative relationships with groups of genes involved in neurodegeneration and cellular metabolism. Increasing adropin expression using transgenesis improved spatial learning and memory, novel object recognition, resilience to exposure to new environments, and reduced mRNA markers of inflammation in old mice. Treatment with synthetic adropin peptide also reversed age-related declines in cognitive functions and affected expression of genes involved in morphogenesis and cellular metabolism. Collectively, these results establish a link between adropin expression and neural energy metabolism and indicate a potential therapy against neurological aging.

Establishing norms for age-related changes in proton T1 of human brain tissue in vivo

1997 ◽  
Vol 15 (10) ◽  
pp. 1133-1143 ◽  
Author(s):  
Seong Cho ◽  
Dana Jones ◽  
Wilburn E. Reddick ◽  
Robert J. Ogg ◽  
R.Grant Steen
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Human Brain Tissue ◽  
Age Related ◽  
Age Related Changes

scholarly journals Adropin expression correlates with aging-related neuropathology in the human brain and improves neuroinflammation and cognitive function in aging mice

2021 ◽  
Author(s):  
Subhashis Banerjee ◽  
Sarbani Ghoshal ◽  
Clemence Girardet ◽  
Kelly M. DeMars ◽  
Changjun Yang ◽  
...  
Keyword(s):  
Cellular Metabolism ◽  
Enrichment Analysis ◽  
Spatial Learning And Memory ◽  
Oligodendrocyte Progenitor Cells ◽  
Protein Markers ◽  
Novel Therapy ◽  
Markers Of Inflammation ◽  
Expression Of Genes ◽  
Age Related ◽  
And Function

Abstract The neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is highly expressed in astrocytes and peaks during critical postnatal periods of brain development. Gene enrichment analysis of transcripts correlating with adropin expression suggests processes relevance to aging-related neurodegenerative diseases that vary with age and dementia state, possibly indicating survivor bias. In people aged <40y and ‘oldold’ (>75y) diagnosed with dementia, adropin correlates positively with genes involved in mitochondrial processes. In the ‘old-old’ without dementia adropin expression correlates positively with morphogenesis and synapse function. Potent neurotrophic responses in primary cultured neurons are consistent with adropin supporting the development and function of neural networks. Adropin expression in the ‘old-old’ also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in those without dementia. How variation in brain adropin expression affects neurological aging was investigated using old (18- month) C57BL/6J mice. In mice adropin is expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia and shows correlative relationships with groups of genes involved in neurodegeneration and cellular metabolism. Increasing adropin expression using transgenesis improved spatial learning and memory, novel object recognition, resilience to exposure to new environments, and reduced mRNA markers of inflammation in old mice. Treatment with synthetic adropin peptide also reversed age-related declines of cognitive functions and affected expression of genes involved in morphogenesis and cellular metabolism. Collectively, these results establish a link between adropin expression and neural energy metabolism and indicate a potential novel therapy against neurological aging.

scholarly journals Carotenoid-Rich Brain Nutrient Pattern Is Positively Correlated With Higher Cognition and Lower Depression in the Oldest Old With No Dementia

2021 ◽  
Vol 8 ◽  
Author(s):  
Jirayu Tanprasertsuk ◽  
Tammy M. Scott ◽  
Aron K. Barbey ◽  
Kathryn Barger ◽  
Xiang-Dong Wang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Sex Education ◽  
Oldest Old ◽  
Univariate Analysis ◽  
Principal Component ◽  
Human Brain Tissue ◽  
Global Deterioration Scale ◽  
Age Related ◽  
Nutrient Patterns ◽  
Composite Scores

Background: Healthy dietary patterns are related to better cognitive health in aging populations. While levels of individual nutrients in neural tissues are individually associated with cognitive function, the investigation of nutrient patterns in human brain tissue has not been conducted.Methods: Brain tissues were acquired from frontal and temporal cortices of 47 centenarians from the Georgia Centenarian Study. Fat-soluble nutrients (carotenoids, vitamins A, E, K, and fatty acids [FA]) were measured and averaged from the two brain regions. Nutrient patterns were constructed using principal component analysis. Cognitive composite scores were constructed from cognitive assessment from the time point closest to death. Dementia status was rated by Global Deterioration Scale (GDS). Pearson's correlation coefficients between NP scores and cognitive composite scores were calculated controlling for sex, education, hypertension, diabetes, and APOE ε4 allele.Result: Among non-demented subjects (GDS = 1–3, n = 23), a nutrient pattern higher in carotenoids was consistently associated with better performance on global cognition (r = 0.38, p = 0.070), memory (r = 0.38, p = 0.073), language (r = 0.42, p = 0.046), and lower depression (r = −0.40, p = 0.090). The findings were confirmed with univariate analysis.Conclusion: Both multivariate and univariate analyses demonstrate that brain nutrient pattern explained mainly by carotenoid concentrations is correlated with cognitive function among subjects who had no dementia. Investigation of their synergistic roles on the prevention of age-related cognitive impairment remains to be performed.

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