From fetus to older age: A review of brain metabolic changes across the lifespan

Cichocka, Monika; Bereś, Anna

doi:10.1016/j.arr.2018.05.005

Cited by 33 publications

(28 citation statements)

References 108 publications

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“…However, it is still not clear what changes in absolute levels of inositol represent – it may be that changes, as reported here, reflect changes in glial metabolism ( Marajanska et al., 2017 ). The decrease in NAA and glutamate turnover after 7 months may suggest that this is the point where rodent brains mature from young adulthood to middle age, as some human studies have shown a decrease in NAA between at this time as formation of new pathways slows down ( Cichoka and Beres, 2018 ), however, further study in humans and rodents is needed to fully understand such changes.…”

Section: Discussionmentioning

confidence: 99%

A longitudinal, multi-parametric functional MRI study to determine age-related changes in the rodent brain

et al. 2020

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As the population ages, the incidence of age-related neurological diseases and cognitive decline increases. To further understand disease-related changes in brain function it is advantageous to examine brain activity changes in healthy aging rodent models to permit mechanistic investigation. Here, we examine the suitability, in rodents, of using a novel, minimally invasive anaesthesia protocol in combination with a functional MRI protocol to assess alterations in neuronal activity due to physiological aging. 11 Wistar Han female rats were studied at 7, 9, 12, 15 and 18 months of age. Under an intravenous infusion of propofol, animals underwent functional magnetic resonance imaging (fMRI) and functional magnetic resonance spectroscopy (fMRS) with forepaw stimulation to quantify neurotransmitter activity, and resting cerebral blood flow (CBF) quantification using arterial spin labelling (ASL) to study changes in neurovascular coupling over time. Animals showed a significant decrease in size of the active region with age (P < 0.05). fMRS results showed a significant decrease in glutamate change with stimulation (ΔGlu) with age (P < 0.05), and ΔGlu became negative from 12 months onwards. Global CBF remained constant for the duration of the study. This study shows age related changes in the blood oxygen level dependent (BOLD) response in rodents that correlate with those seen in humans. The results also suggest that a reduction in synaptic glutamate turnover with age may underlie the reduction in the BOLD response, while CBF is preserved.

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Section: Discussionmentioning

confidence: 99%

A longitudinal, multi-parametric functional MRI study to determine age-related changes in the rodent brain

et al. 2020

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“…Embryologically, the early to mid-gestation period is a critical period for brain growth, with the earliest synapses in the spinal cord developing during early gestation at 6 to 7 weeks [22]. Furthermore, subcortical structures have been shown to develop around mid-gestation at 12 to 22 weeks [23]. Nonetheless, the brain metabolism of the fetus has not been studied.…”

Section: Discussionmentioning

confidence: 99%

Fetal Head Growth during Early to Mid-Gestation Associated with Weight Gain in Mothers with Hyperemesis Gravidarum: A Retrospective Cohort Study

et al. 2020

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The epigenetic impact of malnutrition in mothers with hyperemesis gravidarum (HG) on their offspring has not been fully elucidated. Recently, several reports have demonstrated that children born to mothers with HG were small for gestational age and had low birth weight, reduced insulin sensitivity, and neurodevelopmental delays during childhood. Therefore, we examined the relationship between fetal growth and changes in the maternal body weight in HG cases. A total of 34 patients with HG were hospitalized and delivered at term between 2009 and 2012. The records of 69 cases of pregnant women without a history of HG were extracted after matching their maternal age, parity, pregestational body mass index (BMI), gestational age, and fetal sex ratio with those of the HG group for comparison. The maternal weight gain at term was less in the HG than in the control group. There was no statistical difference in birth weight, placental weight, and ultrasonic fetometric parameters expressed in standard deviation (SD) scores, including biparietal diameter, abdominal circumference, and femur length, between the HG and the control group. Whereas fetal head growth in the HG group was positively associated with maternal weight gain at 20 weeks of gestation only, this association was not observed in the control group. We herein demonstrate that maternal weight gain from the nadir is associated with fetal head growth at mid-gestation. Thus, maternal undernutrition in the first trimester of pregnancy could affect fetal brain growth and development, leading to an increased risk of neurodevelopmental delays in later life.

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“…Normal ageing involves cognitive decline related to widespread neurochemical alterations (Driscoll et al, 2003). These alterations have been studied non-invasively and in vivo using proton MR spectroscopy ( 1 H-MRS), however, the results have been highly variable (for review see: (Haga et al, 2009;Cichocka and Bereś, 2018;Cleeland et al, 2019)).…”

Section: Introductionmentioning

confidence: 99%

“…The most commonly investigated brain metabolites in 1 H-MRS ageing studies are myoinositol (mIns), total creatine (tCr), total choline (tCho), total N-acetylaspartate (tNAA) and glutamate (Glu) (Cichocka and Bereś, 2018). Though results from 1 H-MRS ageing studies have varied, the most consistent results indicate that mIns, tCr and tCho levels increase with age whereas tNAA and Glu levels decrease (Cleeland et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Regional glia-related metabolite levels are higher at older age and scale negatively with visuo-spatial working memory: A cross-sectional proton MR spectroscopy study at 7 tesla on normal cognitive ageing

Lind

Boraxbekk

Petersen

et al. 2019

Preprint

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Proton MR spectroscopy (1H-MRS) has been used to assess regional neurochemical brain changes during normal ageing, but results have varied. Exploiting the increased sensitivity at ultra-high field strength, we performed 1H-MRS in 60 healthy volunteers to asses age-related differences in neuron- and glia-related metabolite levels and their relation to cognitive ageing. Gender was balanced and participants were assigned to a younger, middle and older group according to their age, ranging from 18 to 79 years. They underwent 1H-MRS of anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus and thalamus and performed a visuo-spatial working memory task outside the scanner. Multivariate ANCOVA revealed a significant overall effect of age group on metabolite levels in all brain regions of interest. Considering specific metabolites, elevated levels of glia-related metabolites in older age groups were observed in all brain regions. For the neuron-related metabolites, differences among age groups were only observed in two regions. We found higher levels of total N-acetyl aspartate in hippocampus for the older than the middle group, and lower levels of glutamate in DLPFC in the older than the younger group. Working memory performance correlated negatively with levels of glia-related metabolites for total creatine and total choline in ACC and myo-inositol in hippocampus and thalamus, but not with neuron-related metabolites. Together, the results show that age effects on glia-related metabolites scale with cognitive ageing in multiple brain regions. We conclude that 1H-MRS-derived glia-related markers may be of value in longitudinal studies of brain ageing.Significance statementNeurochemical ageing is an integral component of age-related cognitive decline. Proton MR spectroscopy (1H-MRS) studies of in vivo neurochemical changes across the lifespan have, however, yielded inconclusive results. Due to the higher spectral resolution and sensitivity, 7 tesla 1H-MRS has potential to improve consistency of the results. Here we apply this technique to demonstrate that glia-related metabolites are elevated in older age in anterior cingulate cortex, hippocampus and thalamus with a novel link to cognitive ageing of visuo-spatial working memory. This study is the first to investigate normal ageing in these brain regions using 7 tesla 1H-MRS and the results indicate that glia-related metabolites could be of value in longitudinal studies of cognitive ageing.

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From fetus to older age: A review of brain metabolic changes across the lifespan

Cited by 33 publications

References 108 publications

A longitudinal, multi-parametric functional MRI study to determine age-related changes in the rodent brain

A longitudinal, multi-parametric functional MRI study to determine age-related changes in the rodent brain

Fetal Head Growth during Early to Mid-Gestation Associated with Weight Gain in Mothers with Hyperemesis Gravidarum: A Retrospective Cohort Study

Regional glia-related metabolite levels are higher at older age and scale negatively with visuo-spatial working memory: A cross-sectional proton MR spectroscopy study at 7 tesla on normal cognitive ageing

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