Scientists from the University of North Carolina School of Medicine showed that the mossy cells in the hippocampus regulate the production of new neurons from stem cells. The results of a study, published in the journal Neuron, can shed light on the causes of neurological diseases and help in the creation of effective treatments.
Scientists have found that the regulation of stem cell differentiation into neurons by means of mossy cells is important for normal learning and memory, stress response, and mood regulation. Violation of this neurogenesis is observed in many common diseases, including Alzheimer’s disease, schizophrenia, depression, anxiety, brain injury and some forms of epilepsy. Focus on the mossy cells can be the basis of a new direction of treatment of such disorders.
“The hope is we could manipulate even a small number of mossy cells to restore hippocampal neurogenesis and related brain functions”, – said study senior author Juan Song, PhD.
Mossy cells are themselves a type of neurons that are located in the dentate gyrus of the hippocampus, where neuronal stem cells are also located. Mossy cells, as well as nerve fibers that input various nerve signals to them, have their name because their numerous connection points give them a “mossy” appearance.
What functions are performed by these cells is a long-standing subject of scientists’ disputes. Partly because they are difficult to distinguish from other brain cells. It is known that the mossy cells are important for learning and memorizing and are extremely sensitive to stress. They die off quickly, for example, under the low-oxygen conditions of a stroke or heart attack, or when overstimulated by seizures in temporal lobe epilepsy.
Using advanced tracking techniques on several different strains of genetically modified laboratory mice, Song and her colleagues labeled mossy cells in mouse hippocampi and marked their connections to other brain cells. They found that mossy cells are connected to neuronal stem cells directly via an excitatory pathway and indirectly communicate with stem cells through nearby neurons called interneurons that then connect to stem cells via an inhibitory pathway.
Unexpectedly, Song and her team open that mossy cells can shift the balance of their direct and indirect signaling, thereby dynamically regulating the activity of neuronal stem cells.
In the experiments, Song’s team showed that the moderate mossy cell activity leads to the dominance of indirect signaling and preservation of stem cells at rest, that may lead to a low level of neurogenesis, but the stem cells could be preserved over a long time.
The high mossy cell activity, which could occur with brain stimulation or in a diseased state, causes a direct signaling dominant and kept stem cells in an “activated” state, increasing the level of neurogenesis. However, this can lead to depletion of the stem cell population over time.
Scientists have noticed that the removal of a part of the mossy cells led neural stem cells to increase their activity, and then to a reduction in their number.
The discovery indicates that the loss of mossy cells caused by impairments can be a key factor underlying many pathological diseases with insufficient neurogenesis. This suggests that replacing or otherwise changing the activity of mossy cells can be an effective treatment strategy, says Song.
“We were surprised that this small population of mossy cells could exert such a big impact on stem cell behavior”, – Song said.
Currently, Song and her team, using the knowledge, obtained in this study, will begin to study what is happening to the moss cells in various diseases, and how they might be replaced or changed their activity to treat such diseases.
“We’re beginning to look at how this cell population is changed in Alzheimer’s disease, for example”, – Song said.