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The present study aimed to better understand the role of the neonatal leptin surge, which peaks on postnatal day ( PND)9-10, on the development of the hippocampal formation. Accordingly, male and female rats were administered with a pegylated leptin antagonist on PND9 and the expression of neurones, glial cells and diverse markers of synaptic plasticity was then analysed by immunohistochemistry in the hippocampal formation. Antagonism of the actions of leptin at this specific postnatal stage altered the number of glial fibrillary acidic protein positive cells, and also affected type 1 cannabinoid receptors, synaptophysin and brain-derived neurotrophic factor ( BDNF), with the latter effect being sexually dimorphic. The results indicate that the physiological leptin surge occurring around PND 9-10 is critical for hippocampal formation development and that the dynamics of leptin activity might be different in males and females. The data obtained also suggest that some but not all the previously reported effects of maternal deprivation on hippocampal formation development (which markedly reduces leptin levels at PND 9-10) might be mediated by leptin deficiency in these animals. [ABSTRACT FROM AUTHOR]

It is clear that the prenatal and early neonatal environments are important for determining the metabolic equilibrium in the adult animal, with prenatal/neonatal leptin levels being at least one of the factors involved. Leptin modulates hypothalamic development and, in particular, the neuronal circuits involved in metabolic control. We have recently reported that maternal deprivation (MD) for 24 h on postnatal day (PND) 9 modifies trophic factors and markers of cell turnover and neuronal maturation in the hypothalamus, as well as body weight and circulating leptin levels at PND13, with long- term effects on weight gain and circulating metabolic hormones in the adult. Moreover, these responses are sexually dimorphic. During MD, a dramatic decline in leptin levels is observed; thus, we aimed to determine which of the previously observed changes in markers of hypothalamic development might be attributed to the decline in this metabolic signal. Accordingly, male and female rats were treated with a pegylated leptin antagonist on PND9. In both sexes, hypothalamic signal transducer and activator of transcription 3 activation in response to acute leptin treatment was blocked by the antagonist. In females, hypothalamic mRNA levels for brain-derived neurotrophic factor, cocaine- and amphetamine-regulated transcript and the leptin receptor were increased, as were nestin and vimentin levels. There was also an increase in cell death in the hypothalamus, with a shift towards an anti-apoptotic balance in the Bcl2/BAX ratio. No hypothalamic effects were seen in males. Because antagonism of the actions of leptin at this specific neonatal stage affects hypothalamic cell turnover and maturation in a sex-specific manner, changes in this hormone, at least at this postnatal age, may differentially affect hypothalamic development in males and females, and may explain some of the reported sexually dimorphic responses to modifications in the early nutritional environment. [ABSTRACT FROM AUTHOR]