Perinatal undernutrition modifies cell proliferation and brain-derived neurotrophic factor levels during critical time-windows for hypothalamic and hippocampal development in the male rat
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B Coupé1, I Dutriez-Casteloot, C Breton
1Unité de Neurosciences et Physiologie Adaptatives, Equipe dénutritions maternelles périnatales, EA 4052, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, France.
Insights
Maternal perinatal undernutrition (MPU) alters brain development in male rats, affecting brain-derived neurotrophic factor (BDNF) and cell proliferation in the hypothalamus and hippocampus during critical windows.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Maternal perinatal undernutrition (MPU) is linked to adult metabolic and cognitive diseases.
- The hypothalamus and hippocampus are crucial for neuroendocrine regulation, metabolism, and cognition.
- Early life nutrition significantly impacts brain development and long-term health outcomes.
Purpose of the Study:
- To investigate the effects of maternal food restriction on hypothalamic and hippocampal development in male rat offspring.
- To analyze changes in brain-derived neurotrophic factor (BDNF) and cell proliferation during critical developmental periods.
Main Methods:
- Maternal rats were subjected to a 50% food restriction (FR50) from embryonic day 14 (E14) to postnatal day 21 (P21).
- Protein and mRNA levels of BDNF were measured.
- Cell proliferation was assessed using 5-bromodeoxyuridine (BrdU) incorporation in the hypothalamus and hippocampus.
Main Results:
- FR50 rats showed delayed hippocampal BDNF increase but augmented hypothalamic BDNF levels from E21 to P14.
- Specific alterations in BDNF and BrdU-positive cell counts were observed in hippocampal subregions and hypothalamic nuclei.
- MPU induced changes in the timing of BDNF production and cell proliferation in sensitive developmental windows.
Conclusions:
- Maternal undernutrition alters the developmental trajectory of BDNF and cell proliferation in the rat hypothalamus and hippocampus.
- These perinatal modifications suggest potential long-lasting consequences for neuroendocrine function, metabolism, and cognition.
- Early nutritional interventions may be critical for mitigating adverse developmental programming.
Abstract:
Maternal perinatal undernutrition (MPU) modifies the activity of the hypothalamic-pituitary-adrenal axis and sensitises to the development of metabolic and cognitive adult diseases. Because the hypothalamus and hippocampus are involved in the regulation of neuroendocrine activity, energy metabolism and cognition, we hypothesised that a maternal 50% food restriction (FR50) from day 14 of pregnancy (E14) until postnatal day 21 (P21) would affect the development of these structures in male rat offspring. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) and cell proliferation [analysed by 5-bromodeoxyuridine (BrdU) incorporation] were compared in both control and FR50 rats from E21 to P22. Although the pattern of the evolution of BDNF concentration and cell proliferation throughout development was not strikingly different between groups, several disturbances at specific developmental stages were observed. FR50 rats exhibited a delayed increase of hippocampal BDNF content whereas, in the hypothalamus, BDNF level was augmented from E21 to P14 and associated, at this latter stage, with an increased mRNA expression of TRkB-T2. In both groups, a correlation between BDNF content and the number of BrdU positive cells was noted in the dentate gyrus, whereas opposite variations were observed in CA1, CA2 and CA3 layers, and in the arcuate and ventromedial nuclei. In the hippocampus, P15-FR50 rats showed an increased number of BrdU positive cells in all regions, whereas, at P22, a decrease was observed in the CA2. In the hypothalamus, between E21 and P8, MPU increases the number of BrdU positive cells in all regions analysed and, until P15, marked differences were noticed in the median eminence, the paraventricular nucleus and the arcuate nucleus. Taken together, the results obtained in the present study show that MPU changes the time course of production of BDNF and cell proliferation in specific hippocampal and hypothalamic areas during sensitive developmental windows, suggesting that these early perinatal modifications may have long-lasting consequences.
