Astrocytes are star-shaped cells in the brain that surround brain cells, known as neurons, protecting them from injury and enabling them to function properly. The brain contains billions of cells, each of which communicate between each other for neural circuitry to function properly. This communication is highly dependent on the behaviour of the immune-based brain cells, astrocytes.
However, the mechanisms that create and maintain differences among astrocytes, allowing them to fulfill specialized roles, remains poorly understood. Now, a study from researchers led by the McGill University demonstrates that astrocytes can be adjusted by neurons in response to injury and disease. The team state that their findings show that the brain has a far greater ability to adapt and respond to changes than previously believed and could have significant implications on neuropsychiatric and neurodegenerative disease. The study is published in the journal Science.
Previous studies show that the neuronal network was considered the only important function of astrocytes, and they were seen as mere gap fillers. Astrocytes are now thought to play a number of active roles in the brain, however, including the secretion or absorption of neural transmitters and maintenance of the blood–brain barrier. Following this theory, the concept of a tripartite synapse has now been proposed, referring to the tight relationship occurring at synapses among a presynaptic element, a postsynaptic element and a glial element. It was also believed that astrocytes acquired their properties during the development of the brain and then they were hardwired in their roles. The current study shows that astrocytes are actually incredibly flexible and potentially modifiable, which enables them to improve brain function or restore lost potential caused by disease.
The current study used mouse models to study a specific pathway called the Sonic Hedgehog (SHH) signaling pathway, which is well known in brain development and cancer. Results show that this signaling pathway is used in the adult brain in a completely novel way and was observed inducing disparate changes in astrocytes in different brain regions. Data findings show that neurons actively determine the features of astrocytes in the healthy adult brain and define a role for neuron-derived sonic hedgehog in regulating the molecular and functional profile of astrocytes.
Results show that there is a little dial-like mechanism on astrocytes that enables neurons to adjust astrocytes to ensure they provide the right kind of support. The lab explain that this ‘dial’ is likely used to tune the astrocyte’s response in the normal brain and in diseases like Alzheimer’s or Parkinson’s, as well as injuries such as stroke and trauma. They go on to conclude that this means the molecular and physiological program of astrocytes is not hardwired during neurodevelopment, with them depending on cues from neurons to drive and sustain their specialized properties.
The team surmise that their findings will advance the understanding of fundamental mechanisms that play a role in brain disease. They go on to add that their goal is to see how this mechanism is affected in different brain diseases and determine if it can be harnessed to protect neurons and ultimately preserve brain function. For the future, the researchers state that this data has the potential to impact the understanding of and ultimately future treatments for a number of neurodegenerative diseases.
Source: McGill University Health Centre