Phagocytic Activity of Rat Primary Astrocytes Is Regulated by Insulin and Ganglioside GM1

Abstract

A timely and efficient removal of apoptotic cells and their fragments is essential to maintain tissue homeostasis in normal and pathological conditions. Since the removal of apoptotic substrates is executed by the cells endowed with phagocytic activity, the issue of its regulation is of particular interest. In this work, we studied the effect of two biologically active substances, insulin and ganglioside GM1, on phagocytic activity of rat primary astrocytes. We showed that cell incubation with 1 µM insulin significantly decreased the phagocytic activity of astrocytes (58.5% vs. control), whereas the incubation with 10 µM GM1 caused an increase in phagocytic activity (133.4% vs. control). Preincubation of brain astrocytes with GM1 completely blocked the inhibitory effect of insulin. These results can be instrumental in developing novel therapeutic strategies for the treatment of neurodegenerative diseases accompanied by the emergence of apoptotic substrates.

Regulation of the phagocytic activity of astrocytes by neuroimmune mediators endogenous to the central nervous system

“…While modulators of microglial phagocytic activity have been studied extensively and include a range of pathology-associated molecules (e.g., complement C1q, C3b) [ 30 ] and inflammatory mediators (e.g., lipopolysaccharide (LPS), IL-1β, and interferon (IFN)-γ) [ 31 – 33 ], regulation of this function in astrocytes is not well understood. Studies have shown that astrocyte phagocytic activity can be modulated by Aβ [ 34 ], α-synuclein preformed fibrils [ 35 ], LPS [ 36 ], hemoglobin [ 37 ], synthetic steroid tibolone [ 38 ], glucocorticoids [ 39 ], insulin, and ganglioside GM1 [ 40 ]. However, regulation of this critical astrocyte function by immune mediators that are endogenous to the CNS is largely unknown except for a single report by Kalmar et al [ 36 ].…”