Abstract
A deficiency in B-vitamins is known to lead to persistent developmental defects in various organs during early life. The nervous system is particularly affected with functional retardation in infants and young adults. In addition, even if in some cases no damage appears evident in the beginning of life, correlations have been shown between B-vitamin metabolism and neurodegenerative diseases. However, despite the usual treatment based on B-vitamin injections, the neurological outcomes remain poorly rescued in the majority of cases, compared with physiological functions. In this study, we explored whether a neonatal stimulation of neurogenesis could compensate atrophy of specific brain areas such as the hippocampus, in the case of B-vitamin deficiency. Using a physiological mild transient hypoxia within the first 24 h after birth, rat-pups, submitted or not to neonatal B-vitamin deficiency, were followed until 330-days-of-age for their cognitive capacities and their hippocampus status. Our results showed a gender effect since females were more affected than males by the deficiency, showing a persistent low body weight and poor cognitive performance to exit a maze. Nevertheless, the neonatal stimulation of neurogenesis with hypoxia rescued the maze performance during adulthood without modifying physiological markers, such as body weight and circulating homocysteine. Our findings were reinforced by an increase of several markers at 330-days-of-age in hypoxic animals, such as Ammon’s Horn 1hippocampus (CA1) thickness and the expression of key actors of synaptic dynamic, such as the NMDA-receptor-1 (NMDAR1) and the post-synaptic-density-95 (PSD-95). We have not focused our conclusion on the neonatal hypoxia as a putative treatment, but we have discussed that, in the case of neurologic retardation associated with a reduced B-vitamin status, stimulation of the latent neurogenesis in infants could ameliorate their quality of life during their lifespan.
Highlights
Methyl donor deficiency during the perinatal period is known to induce dramatic structural and functional consequences in various organs of newborns
Previous studies have already shown that a deficiency in B-vitamins during gestation and lactation leads to reduced one-carbon metabolism markers and global body status in the young [16,28]
Females did not follow such a restoration of body weight during adulthood since significantly lower body weights were measured for MDD and MDD-H females compared to controls at each age-point from D40 to D205
Summary
Methyl donor deficiency during the perinatal period is known to induce dramatic structural and functional consequences in various organs of newborns. A mechanism described as “fetal programming” or “Barker theory” predicts that if a disruption occurs during the development and maturation of a cellular circuit or an organ, the functional outcomes will be dramatically disturbed during the lifespan [12,13,14,15]. This was shown for the brain in case of micronutrients and methyl donor deficiencies [16,17,18,19]. Our global objective was not to propose a treatment with hypoxia in the case of positive results, but to highlight putative brain reactions and propose molecular targets in order to complement the classical B-vitamin treatments
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