Neurotrophins in astrocyte, new roles beyond survival and death

CRAGNOLINI, ANDREA BEATRIZ

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2019

Neurotrophins can influence multiple cell functions depending on the cell context and the specific receptors they interact with. These trophic factors have been extensively studied in neurons for their ability to support neuronal survival via Trk receptors and to induce apoptosis via p75NTR. However, neurotrophins and their receptors are expressed in other cellular populations, such as glia, in which their functions are starting to be elucidated. Astrocytes represent a large population of glial cells that produce and secrete neurotrophins, especially after a lesion in the central nervous system (CNS). Astrocytes are also the target of the neurotrophins since they express their receptors. In astrocytes, we demonstrated that the expression of the p75NTR receptor increases after inducing seizures in rodents or after inflicting a mechanical injury in vitro. The treatment of astrocytic primary cultures with the neurotrophin NGF caused a reduction in the number of cells via activation of the p75NTR receptor but, unlike neurons, it was not associated with apoptosis. Rather, the activation of p75NTR by NGF interfered with the expression of cyclins and their association with specific cyclin-dependent kinases, which are associated with the progression through the cell cycle. These results suggest that the activation of p75NTR promotes withdrawal of astrocytes from the cell cycle, which may have important consequences during development or after injury. Next, we wondered if astrocytes show specific brain region-associated responses. We used an in vitro model of mechanical injury (scratch injury) to evaluate the wound closure in monolayers of cells obtained from the cortex, hippocampus and striatum. We observed that migration and proliferation varied between astrocytes obtained from different regions of the brain, as well as their responses to NGF and BDNF which potentiate wound closure. These results reinforce the idea that astrocytes constitute a heterogeneous cell population and that their brain-region origin may determine their responses to a lesion and to neurotrophins.