The central effects of cyclo-glycine-proline on lactation regulation and neuroplasticity in lactating rats

Abstract

Background and aims: Post-natal brain development greatly depends on nutrition and maternal care. cGP, an IGF-1 derived peptide, has been shown to improved cognition through promoting of neuroplasticity in brain circuities. In a previous study, oral administration of cGP-treatment to dams resulted in the enhancement in learning and memory in young adult offspring cognition (Mallah et al, 2016). The improved brain development in the offspring with maternal cGP treatment may also related to better nutrition due to an improvement in lactation and/or an improvement in maternal care behaviors. The present study thus aims to investigate potential role for cGP in the neuroplasticity in the dams that potentially associated with better maternal care and that involved in central regulation of lactation. Methods: Brain sections were collected from the dams treatment with either the placebo (n=16) or cGP (n=16) at postpartum day 23 (Mallah et al, 2016). Synaptic markers were measured by free-floating immunohistochemistry including synaptophysin, a protein present in the vesicles of presynapse and GluR-1, to label glutamatergic neuroplasticity. Immuno-staining of PRLR was used to investigate changes of the central regulation of lactation. ImageJ software was used to measure different parameters for each marker in the brain regions of hippocampus, striatum, frontal cortex and hypothalamus. Finally, Western blot was used to measure relative concentrations of protein markers such as tyrosine hydroxylase, assessing dopaminergic neuroplasticity, and GFAP, quantifying the change in astrocyte number. The differences between the groups were analyzed using Prism statistical software. Results: Oral administration of cGP improved synaptophysin in the hippocampus and hypothalamus and promoted glutamatergic neuroplasticity in the striatum, with a trend toward an improvement of glutamatergic neuroplasticity in the hippocampus. There was no difference in PRLR staining in the hypothalamus. Finally cGP treatment did not affect dopaminergic neuroplasticity nor did it affect astrocytes number. Conclusion: Maternal treatment of cGP improved neuroplasticity in the brain regions involved in working memory. The enhanced glutamate neurotransmission may be an indirect evidence for better maternal care. cGP did not involve prolactin associated central regulation in lactation.