Prolactin Receptor Deficiency Promotes Hypomyelination in White Matter Tracts During Postnatal Central Nervous System Maturation in Mice

A large wave of myelination in the central nervous system (CNS) of mammals occurs during postnatal development, coinciding with the lactation period. High prolactin (PRL) levels are present in maternal milk; however, the role of milk PRL in lactating offspring remains under-investigated. This study explores whether PRL influences myelination during postnatal development in lactating and prepubertal mice. PRL and its receptors (PRLRs) are found in white matter (WM) tracts of lactating mice, but PRL mRNA is not expressed locally, supporting that the hormone derives from maternal milk, since the pituitary gland from neonatal mice does not secrete PRL. The absence of PRLRs (in PRLR knockout [KO] mice) results in a hypomyelinated phenotype characterized by a reduced corpus callosum volume, decreased myelin staining in WM tracts (cingulum, corpus callosum and dorsal fornix), lower myelin basic protein (MBP) expression levels, and a reduced number of oligodendroglial cells, as revealed by fewer OLIG2-positive cells in PRLR-KO nursing pups at postnatal day (PD) 12. The hypomyelination observed in PRLR-KO nursing pups continues into the prepubertal stage (PD28), when locomotor alterations (reduced distance traveled and decreased velocity of movements) manifest in PRLR-KO mice. These findings show that the lack of PRL signaling leads to brain hypomyelination in neonatal mice and negatively affects locomotor function at the prepubertal stage, thereby supporting the notion that PRL is required for adequate myelination during postnatal development.