The mechanisms of complex milk lipid (CML) supplementation on memory improvement during development

Abstract

Early life nutrition is one of the most important factors affecting neurodevelopment in mammals. Components found in milk such as complex lipids were shown to have an impact on cognitive development including learning and memory. A previous study revealed that ganglioside-containing complex milk lipid (CML) supplementation, given during the critical period of development, moderately improved spatial learning and novelty object recognition in young normal rats (Vickers et al., 2009). However, the mechanisms underlying these learning and memory improvements have not yet been investigated. The present study therefore aims to evaluate potential mechanisms that could underlie the improvements in spatial learning and novelty recognition in CMLsupplemented young normal rats, during development. Specifically, possible changes in neuroplasticity and vascular remodelling were examined, particularly in brain regions closely associated with learning and memory, such as the hippocampus and striatum. Brain tissues from 80-day old male Wistar rats in the control group (n=16) and those in the group supplemented with high dose CML (n=16) – as used in the previous study – were obtained (Vickers et al., 2009). Immunohistochemistry staining of markers of neuroplasticity and of blood vessels – for assessment of vascular remodelling – in paraffinembedded brain tissue sections were conducted. Protein markers used include synaptophysin to track synaptic vesicles for evaluation of presynaptic neuroplasticity, tyrosine hydroxylase (TH) to tag dopaminergic neurons and terminals for assessment of dopaminergic neuroplasticity and finally, GluR-1s as a marker of glutamatergic neuroplasticity. Using two different image analyses software, ImageJ and SigmaScan Pro, parameter measures were obtained and compared between the two groups. Our findings indicate that CML supplementation may promote neuroplasticity in the CA3 hippocampal region of young normal rats, during development. CML supplementation may also be associated with changes in dopaminergic pathway, as indicated by the higher striatal/nigral TH density ratio and the trend of lowered TH in the substantia nigra of CML-supplemented rats. However, absence of the trend in the neuronal terminals located in striatum infers that CML supplementation has no effect on dopamine output of young normal rats. Finally in our study, CML-supplementation did not appear to be associated with glutamatergic neuroplasticity nor with vascular remodelling during development.