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Age and energy intake interact to modify cell stress pathways and stroke outcome.

ABSTRACT: OBJECTIVE:Age and excessive energy intake/obesity are risk factors for cerebrovascular disease, but it is not known if and how these factors affect the extent of brain damage and outcome in ischemic stroke. We therefore determined the interactions of age and energy intake on the outcome of ischemic brain injury, and elucidated the underlying mechanisms. METHODS:We utilized a novel microchip-based immunoaffinity capillary electrophoresis technology to measure a panel of neurotrophic factors, cytokines, and cellular stress resistance proteins in brain tissue samples from young, middle-aged, and old mice that had been maintained on control or energy-restricted diets prior to middle cerebral artery occlusion and reperfusion. RESULTS:Mortality from focal ischemic stroke was increased with advancing age and reduced by an intermittent fasting (IF) diet. Brain damage and functional impairment were reduced by IF in young and middle-aged mice, but not in old mice. The basal and poststroke levels of neurotrophic factors (brain-derived neurotrophic factor and basic fibroblast growth factor), protein chaperones (heat shock protein 70 and glucose regulated protein 78), and the antioxidant enzyme heme oxygenase-1 were decreased, whereas levels of inflammatory cytokines were increased in the cerebral cortex and striatum of old mice compared with younger mice. IF coordinately increased levels of protective proteins and decreased inflammatory cytokines in young, but not in old mice. INTERPRETATION:Reduction in dietary energy intake differentially modulates neurotrophic and inflammatory pathways to protect neurons against ischemic injury, and these beneficial effects of IF are compromised during aging, resulting in increased brain damage and poorer functional outcome.

SUBMITTER: Arumugam TV

PROVIDER: S-EPMC2844782 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Age and energy intake interact to modify cell stress pathways and stroke outcome.

Arumugam Thiruma V TV Phillips Terry M TM Cheng Aiwu A Morrell Christopher H CH Mattson Mark P MP Wan Ruiqian R

Annals of neurology 20100101 1

<h4>Objective</h4>Age and excessive energy intake/obesity are risk factors for cerebrovascular disease, but it is not known if and how these factors affect the extent of brain damage and outcome in ischemic stroke. We therefore determined the interactions of age and energy intake on the outcome of ischemic brain injury, and elucidated the underlying mechanisms.<h4>Methods</h4>We utilized a novel microchip-based immunoaffinity capillary electrophoresis technology to measure a panel of neurotrophi ...[more]

PMID: 20186857

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Project description:IntroductionPreterm birth (PTB) is closely associated with atypical cerebral cortical development and cognitive impairment. Early exposure to extrauterine life often results in atypical environmental and biological experiences that co-occur, including early life stress (ELS) and systemic inflammation. Understanding how these experiences interact to shape cortical development is an essential prerequisite to developing therapeutic interventions that will work in the complex postnatal environment of the preterm infant. Here, we studied the effects of a murine model of infection and ELS on the neonatal cortex transcriptome.MethodsWe used a mouse model of infection (1 mg/kg LPS at postnatal day (P)3) +/- ELS (modified maternal separation; MMS on days P4-P6) at timepoints with neurodevelopmental relevance to PTB. We used 4 groups: control, LPS, MMS and LPS + MMS. Cortices were dissected at P6 for 3'RNA sequencing.ResultsLPS exposure resulted in reduced weight gain and increased expression of inflammation-associated genes in the brain. More genes were differentially expressed following LPS (15) and MMS (29) than with LPS + MMS (8). There was significant overlap between the LPS and MMS datasets, particularly amongst upregulated genes, and when comparing LPS and MMS datasets with LPS + MMS. Gene Ontology terms related to the extracellular matrix and cytokine response were enriched following MMS, but not following LPS or LPS + MMS. 26 Reactome pathways were enriched in the LPS group, none of which were enriched in the LPS + MMS group. Finally, a rank-rank hypergeometric overlap test showed similarities, particularly in upregulated genes, in the LPS and MMS conditions, indicating shared mechanisms.ConclusionLPS and MMS interact to modify the cortical transcriptome in the neonatal period. This has important implications for understanding the neural basis of atypical cortical development associated with early exposure to extrauterine life.

Project description:Oily fish, an important source of marine n-3 long-chain polyunsaturated fatty acids (LCPUFA), has shown to reduce cardiometabolic risk in adults. Whether maternal fish intake affects offspring metabolic health is less established, especially among high-risk pregnancies. We aimed to examine the association of fish intake in pregnancy with offspring metabolic health who were either exposed or unexposed to gestational diabetes mellitus (GDM). Our study included 1234 mother-offspring dyads (608 with a GDM index pregnancy and 626 control dyads) nested within the Danish National Birth Cohort, which is a prebirth cohort. Maternal seafood and marine n-3 LCPUFA consumption was quantified by a food frequency questionnaire (gestational week 25) and a sub-sample with interview data (weeks 12 and 30). The offspring were clinically examined at 9⁻16 years, including a Dual energy X-ray Absorptiometry (DXA) scan and a fasting blood sample. We calculated multivariable effect estimates and 95% confidence intervals (CI) for anthropometric, adiposity, and metabolic parameters. The median (IQR) intake of total seafood was 23(24) g/day. We found largely no association for total seafood and marine n-3 LCPUFA with offspring metabolic parameters in either group. Using interview data, GDM-exposed women reporting no fish in week 12 and 30 (versus intake >2 times/week) had offspring with a higher Body Mass Index (BMI) (ratio of geometric means (RGM): 1.28, 95% CI: 1.06, 1.55), waist circumference (RGM: 1.22, 95% CI: 1.05, 1.40), triglycerides (RGM: 1.77, 95% CI: 1.03, 3.03), and homeostatic model assessment of insulin resistance HOMA-IR (RGM: 2.16, 95% CI: 1.17, 3.97). We found no associations of n-3 LCPUFA and seafood intake with offspring metabolic outcomes. However, GDM-exposed women who consistently reported eating no fish had offspring with a poorer metabolic profile. Fish intake in pregnancy may mitigate some adverse effects of intrauterine hyperglycemia, however, these findings need replication in better powered studies.

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Age and energy intake interact to modify cell stress pathways and stroke outcome.

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Age and energy intake interact to modify cell stress pathways and stroke outcome.

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