Microglial responses to physiological change: osmotic stress elevates DNA synthesis of neurohypophyseal microglia

We were interested to discover whether microglia could play a role in the remodelling of the adult CNS or participate in adaptations to physiological rather than pathological changes. We have studied microglia in the neurohypophysis of adult mice since microglia normally interact with neurons in this tissue and the biochemical and anatomical consequences of osmotic stress on the neurohypophysis are well known. In this study, we have examined microglial immuno-phenotype and numbers synthesizing DNA in the neurohypophysis of adult mice to establish whether these cells respond to progressive osmotic stress. Neurohypophyseal F4/80+ microglia underwent a large synchronous burst of DNA synthesis 48 h after initiation of osmotic stress (drinking 2.5% saline). The labelling index (percentage of F4/80+ cells labelled by [3H]thymidine) 1 h after injection the isotope rose to 17% from a control value of less than 1%. On the third day of treatment the labelling index had returned to control levels. In contrast, non-microglia cells in the neurohypophysis and microglial cells elsewhere in the brain did not show this response. The increase in DNA synthesis was not accompanied by signs of microglia activation commonly observed in inflammatory models. They did not acquire an "activated" or "hypertrophic" morphology, nor was their staining with a panel of antibodies greatly altered. A small up-regulation of CD45 expression was the only phenotypic change detected. Thus, neurohypophyseal microglia respond to increased neurosecretory activity during the adaptation to osmotic stress in a distinctive way which differs from microglia reactions to inflammatory stimuli elsewhere in the CNS.