The Stimulation of Neurogenesis Improves the Cognitive Status of Aging Rats Subjected to Gestational and Perinatal Deficiency of B9–12 Vitamins

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.

Neonatal stimulation of the thyroid gland with iodine or suppression during adolescence with triiodothyronine changes the prevalence of autoimmune thyroiditis in BB rats

OBJECTIVE: Changes in the functional state of beta cells by neonatal stimulation or adolescent suppression have reduced the incidence of type 1 diabetes mellitus in animal models. The aim of this study was to evaluate the effect of manipulation of the activity of the thyroid gland by neonatal stimulation or by adolescent suppression on the prevalence of spontaneous autoimmune thyroiditis (AIT) in rats. METHODS: Bio-Breeding/Worcester (BB) rats were treated neonatally with sodium iodine (NaI) or thyroid stimulating hormone (TSH), or during adolescence by triiodothyronine (T(3)), and the lymphocytic infiltration in the thyroid gland was evaluated. RESULTS: Neonatal treatment with NaI decreased the prevalence of AIT to 32+/-9% compared with 66+/-5% in the controls (P<0.002), mainly caused by a reduction among the female rats (13+/-9% vs 52+/-8%, P<0.006). TSH had no effect. Post neonatal suppression of the thyroid gland by T(3) had a biphasic response. Early in adolescence the overall prevalence was 14+/-7% compared with 66+/-5% in the controls (P<10(-5)); for female rats AIT was prevented (0+/-0%) compared with 52+/-8% in the controls (P<0.0003) and in male rats the values were 29+/-13% compared with 80+/-6% in the controls (P<0.001). Treatment with T(3) later in adolescence increased the overall prevalence to 81+/-7% compared with 66+/-5% in the controls (not significant). For female rats the prevalence increased to 78+/-9% compared with 52+/-8% in the controls (P=0.04). The degree of thyroiditis among the affected animals was similar in all groups. CONCLUSION: Neonatal stimulation of the thyroid gland by iodine or early adolescent suppression by T(3) reduced the prevalence of AIT whereas T(3) given later increased the prevalence of thyroiditis in rats. Thyroid activity at various ages seems to be of importance for the development of autoimmune thyroiditis.