Neonatal hyperglycemia alters the neurochemical profile, dendritic arborization and gene expression in the developing rat hippocampus

Rao, Raghavendra; Nashawaty, Motaz; Fatima, Saher; Ennis, Kathleen; Tkáč, Ivan

doi:10.1002/nbm.3910

Cited by 17 publications

(16 citation statements)

References 49 publications

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“…The hippocampus was chosen for its critical role in cognitive functions by regulating learning, memory encoding, memory consolidation, and spatial navigation. In addition, the hippocampus is known to be vulnerable to different adverse effects, such as stress, 43 neonatal iron deficiency, 44 hyperglycemia, 45 or exposure to drugs 46 . Twelve female and 12 male mice used in protocol I were divided equally into two groups (control and exposed to 16.4 T).…”

Section: Resultsmentioning

confidence: 99%

Long‐term behavioral effects observed in mice chronically exposed to static ultra‐high magnetic fields

Tkáč

Benneyworth

Nichols-Meade

et al. 2021

Magnetic Resonance in Med

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Purpose The primary goal of this study was to investigate whether chronic exposures to ultra‐high B0 fields can induce long‐term cognitive, behavioral, or biological changes in C57BL/6 mice. Methods C57BL/6 mice were chronically exposed to 10.5‐T or 16.4‐T magnetic fields (3‐h exposures, two exposure sessions per week, 4 or 8 weeks of exposure). In vivo single‐voxel 1H magnetic resonance spectroscopy was used to investigate possible neurochemical changes in the hippocampus. In addition, a battery of behavioral tests, including the Morris water‐maze, balance‐beam, rotarod, and fear‐conditioning tests, were used to examine long‐term changes induced by B0 exposures. Results Hippocampal neurochemical profile, cognitive, and basic motor functions were not impaired by chronic magnetic field exposures. However, the balance‐beam–walking test and the Morris water‐maze testing revealed B0‐induced changes in motor coordination and balance. The tight‐circling locomotor behavior during Morris water‐maze tests was found as the most sensitive factor indexing B0‐induced changes. Long‐term behavioral changes were observed days or even weeks subsequent to the last B0 exposure at 16.4 T but not at 10.5 T. Fast motion of mice in and out of the 16.4‐T magnet was not sufficient to induce such changes. Conclusion Observed results suggest that the chronic exposure to a magnetic field as high as 16.4 T may result in long‐term impairment of the vestibular system in mice. Although observation of mice may not directly translate to humans, nevertheless, they indicate that studies focused on human safety at very high magnetic fields are necessary.

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Section: Resultsmentioning

confidence: 99%

Long‐term behavioral effects observed in mice chronically exposed to static ultra‐high magnetic fields

Tkáč

Benneyworth

Nichols-Meade

et al. 2021

Magnetic Resonance in Med

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“…In experimental settings, it has been shown that mechanisms of cerebral injury related to hyperglycemia include microglial activation, neuronal and glial apoptosis; hyperglycemia seems particularly prone to involve the hippocampus and the frontal cortex [20, 21]. In diabetic children, hyperglycemia is considered to be more detrimental for the developing brain than hypoglycemia [22], and asymptomatic hyperglycemia is associated with acute slowing of brain activity on the electroencephalogram [23].…”

Section: Discussionmentioning

confidence: 99%

Early Hyperglycemia in Very Preterm Infants Is Associated with Reduced White Matter Volume and Worse Cognitive and Motor Outcomes at 2.5 Years

et al. 2022

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Introduction: Hyperglycemia in very preterm infants is associated with increased morbidity and mortality. We aimed to investigate potential associations between early hyperglycemia, neonatal cerebral magnetic resonance imaging (MRI), and neurodevelopment at 2.5 years. Methods: The study population included 69 infants with gestational age (GA) 22.3–31.9 weeks (n = 29 with GA <28 weeks), born 2011–2014. Plasma glucose concentrations during the first week were checked according to clinical routines. Hyperglycemia was defined as glucose concentrations above 8.3 mmol/L (150 mg/dL) and above 10 mmol/L (180 mg/dL), respectively, categorized as the highest glucose days 0–2, number of days above 8.3 and 10 mmol/L, and prolonged (yes/no) 2 days or more above 8.3 and 10 mmol/L. The MRI analysis included morphological assessment, regional brain volumes, and assessment of apparent diffusion coefficient (ADC). Neurodevelopmental impairment (NDI) developed in 13 of 67 infants with available outcomes, of which 57 were assessed with the Bayley-III. Univariate and multiple linear and logistic regressions were performed with adjustments for GA, birth weight z-scores, and illness severity expressed as days on mechanical ventilation. Results: Hyperglycemia above 8.3 mmol/L and 10 mmol/L was present in 47.8% and 31.9% of the infants. Hyperglycemia correlated independently with lower white matter volume, but not with other regional brain volumes, and was also associated with lower ADC values in white matter. Hyperglycemia also correlated with lower Bayley-III cognitive and motor scores in infants with GA <28 weeks, but there was no significant effect on NDI. Conclusion: Early hyperglycemia is associated with white matter injury and poorer neurodevelopment in very preterm infants.

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“…Lower NAAG and Glu/Gln ratio, along with lower lactate, indicate decreased neuronal activity in the formerly iron-deficient hippocampus. 104,105 However, in the setting of lower taurine, decreased lactate also could indicate decreased oxidative glucose metabolism. 78 Consistent with this, Glut1 gene and protein expression is decreased in the formerly iron-deficient hippocampus, suggesting decreased brain glucose uptake.…”

Section: Evidence For Persistently Impaired Energy Metabolism Due To mentioning

confidence: 99%

The Effects of Early-Life Iron Deficiency on Brain Energy Metabolism

et al. 2020

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Iron deficiency (ID) is one of the most prevalent nutritional deficiencies in the world. Iron deficiency in the late fetal and newborn period causes abnormal cognitive performance and emotional regulation, which can persist into adulthood despite iron repletion. Potential mechanisms contributing to these impairments include deficits in brain energy metabolism, neurotransmission, and myelination. Here, we comprehensively review the existing data that demonstrate diminished brain energetic capacity as a mechanistic driver of impaired neurobehavioral development due to early-life (fetal-neonatal) ID. We further discuss a novel hypothesis that permanent metabolic reprogramming, which occurs during the period of ID, leads to chronically impaired neuronal energetics and mitochondrial capacity in adulthood, thus limiting adult neuroplasticity and neurobehavioral function. We conclude that early-life ID impairs energy metabolism in a brain region- and age-dependent manner, with particularly strong evidence for hippocampal neurons. Additional studies, focusing on other brain regions and cell types, are needed.

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Neonatal hyperglycemia alters the neurochemical profile, dendritic arborization and gene expression in the developing rat hippocampus

Cited by 17 publications

References 49 publications

Long‐term behavioral effects observed in mice chronically exposed to static ultra‐high magnetic fields

Long‐term behavioral effects observed in mice chronically exposed to static ultra‐high magnetic fields

Early Hyperglycemia in Very Preterm Infants Is Associated with Reduced White Matter Volume and Worse Cognitive and Motor Outcomes at 2.5 Years

The Effects of Early-Life Iron Deficiency on Brain Energy Metabolism

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