![]() ![]() In addition to region-specific differences in gene expression, astrocyte diversity has also been shown within single brain regions. Unique gene profiles have been identified between astrocytes of the cortex, striatum, brainstem, and hippocampus. Although early transcriptomic studies identified genes shared in all astrocytes throughout the brain or changes in gene expression in a particular region over time, the recent studies have identified transcriptional differences between astrocytes of different regions and point to inherent heterogeneity between different astrocyte populations. Insight into the unique molecular profiles of different astrocyte populations has been achieved from a number of recent studies, and there is now substantial evidence that astrocytes are a diverse and heterogeneous cell type in the brain. However, while there have been a number of important insights into the functional diversity of astrocytes, the particular molecular profiles that govern this diversity remain elusive. These are, but a few examples of the myriad functions of astrocytes that have been recently elucidated. There is also evidence that astrocytes sense and respond to neurons via calcium-mediated mechanisms that result in secreted neuromodulators to regulate circuit activity. Disruptions in astrocytic proteins, such as the inward rectifying potassium channel K ir4.1, produce circuit abnormalities throughout the CNS, including in the lateral habenula, striatum, and spinal cord, which are implicated in neurological diseases, such as depression, Huntington’s disease, and amyotrophic lateral sclerosis, respectively. In addition to their roles in synapse formation and maturation, astrocytes are also vital for neuronal circuit function through their regulation of the extracellular ionic environment. These include both astrocyte-secreted molecules, such as SPARC, hevin, thrombospondins, and chordin-like 1, whose presence regulates the insertion of specific receptors into developing synapses, and direct astrocyte–neuron contact via neuroligin/neurexin linkages, which also regulates astrocyte morphogenesis. Astrocytes are required for synapses to form between neurons, and a number of studies have identified astrocyte-derived molecules that are required for the formation and function of individual synapses. Astrocytes are no longer relegated to the sidelines as monolithic “support cells”, and crosstalk between astrocytes and neurons is now known to be required for a number of important processes. Here, we discuss Shh signaling and emerging data that point to essential roles for this pleiotropic signaling pathway in regulating various functional properties of astrocytes in the healthy and injured brain.Īstrocytes are the most abundant glial cells in the brain and are vital for normal brain function. Notably, Shh signaling is active only in discrete subpopulations of astrocytes distributed throughout the brain, a feature that has potential to yield novel insights into functional specialization of astrocytes. Well established as a powerful regulator of diverse neurodevelopmental processes in the embryonic nervous system, its functional significance in astrocytes is only beginning to be revealed. Emerging studies have identified the Sonic hedgehog (Shh) signaling pathway as an essential regulator of the molecular identity and functional properties of astrocytes. The recognition that these cells are integral components of various processes, including synapse formation, modulation of synaptic activity, and response to injury, underscores the need to identify the molecular signaling programs orchestrating these diverse functional properties. Astrocytes are complex cells that perform a broad array of essential functions in the healthy and injured nervous system.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |