Researchers validate microglia role in reducing neurogenesis due to epileptic seizures.


The mission of neural stem cells located in the hippocampus, one of the main regions of the brain, is to generate new neurons during the adult life of mammals, including human beings, of course, and their function is to participate in certain types of learning and responses to anxiety and stress.

Now, using an epilepsy model in genetically modified mice researchers from the University of the Basque Country have discovered that hippocampal neural stem cells stop generating new neurons and are turned into reactive astrocytes, a cell type that promotes inflammation and alters communication between neurons.  The opensource study is published in the journal Cell Stem Cell.

This research work has also made it possible to confirm the hypothesis in a previous piece of research by these researchers; this hypothesis established that even though neuronal hyperexcitation does not go as far as to cause convulsions, it does induce the massive activation of neural stem cells and their resulting premature exhaustion; as a result, neurogenesis (generation of new neurons) in the hippocampus ends up chronically reduced.

The team state that this discovery has enabled better understanding of how neural stem cells function.  The current study showed that in addition to generating neurons and astrocytes, neural stem cells in the adult hippocampus can generate reactive astrocytes following an epileptic seizure.

Even though the work has been carried out on experimental animals, the researchers state that this discovery has clear implications in clinical practice and in the quest for new therapies for epilepsy given that the generation of new neurons (neurogenesis) is a process that is negatively affected in epileptic seizures located in the hippocampus.

The team hypothesize that If the population of neural stem cells can be preserved and their capacity to generate new neurons in humans, it may be possible to prevent the development of certain symptoms associated with epilepsy and very likely to mitigate the damage that is caused in the hippocampus and now plan to investigate this.

Source:  University of the Basque Country

 

Adult hippocampal neurogenesis is believed to maintain a range of cognitive functions, many of which decline with age. We recently reported that radial neural stem cells (rNSCs) in the hippocampus undergo activation-dependent conversion into astrocytes, a mechanism that over time contributes to a reduction in the rNSC population. Here, we injected low and high levels of kainic acid (KA) in the dentate gyrus to assess whether neuronal hyperexcitation, a hallmark of epileptic disorders, could accelerate this conversion. At low levels of KA, generating epileptiform activity without seizures, we indeed found increased rNSC activation and conversion into astrocytes. At high levels, generating sustained epileptic seizures, however, we find that rNSCs divide symmetrically and that both mother and daughter cells convert into reactive astrocytes. Our results demonstrate that a threshold response for neuronal hyperexcitation provokes a dramatic shift in rNSC function, which impairs adult hippocampal neurogenesis in the long term.  Neuronal Hyperactivity Accelerates Depletion of Neural Stem Cells and Impairs Hippocampal Neurogenesis.  Encinas et al 2015.

Adult hippocampal neurogenesis is believed to maintain a range of cognitive functions, many of which decline with age. We recently reported that radial neural stem cells (rNSCs) in the hippocampus undergo activation-dependent conversion into astrocytes, a mechanism that over time contributes to a reduction in the rNSC population. Here, we injected low and high levels of kainic acid (KA) in the dentate gyrus to assess whether neuronal hyperexcitation, a hallmark of epileptic disorders, could accelerate this conversion. At low levels of KA, generating epileptiform activity without seizures, we indeed found increased rNSC activation and conversion into astrocytes. At high levels, generating sustained epileptic seizures, however, we find that rNSCs divide symmetrically and that both mother and daughter cells convert into reactive astrocytes. Our results demonstrate that a threshold response for neuronal hyperexcitation provokes a dramatic shift in rNSC function, which impairs adult hippocampal neurogenesis in the long term. Neuronal Hyperactivity Accelerates Depletion of Neural Stem Cells and Impairs Hippocampal Neurogenesis. Encinas et al 2015.

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