Ernst A, Alkass K, Bernard S, Salehpour M, Perl S, Tisdale J, Possnert G, Druid H, Frisén J.
Neurogenesis in the striatum of the adult human brain.
Cell. 2014 Feb 27;156(5):1072-83. Epub 2014 Feb 20
PubMed.
Joana Gil-Mohapel Island Medical Program, University of British Columbia AND Division of Medical Sciences, University of Victoria
Posted:
It was well known that the human brain retains a certain degree of plasticity throughout postnatal and adult life. Adult hippocampal neurogenesis has been known to occur in the human brain since the pioneer study by Eriksson and colleagues (Eriksson et al., 1998), and neuroscientists speculate that the occurrence of neurogenesis in that brain region may be important in the role that the hippocampus plays in learning and memory. The study by Ernst et al. adds to this by showing the occurrence of postnatal neurogenesis in a different brain region, the striatum, thus illustrating that the human brain is indeed much more plastic than we had originally thought. That new neurons generated in the subventricular zone migrate not to the olfactory bulb (as they do in rodents), but rather to the adjacent striatum, where they differentiate into a particular neuronal population (interneurons) is surprising. This is a very exciting finding as it opens new avenues for the development of potential restorative therapeutic approaches that can utilize the endogenous neurogenic capacity of the brain to replace damaged or degenerating neurons within this brain region.
I was very convinced by the detailed analysis the authors performed in this study using the Carbon-14 dating technique. Further to that, they were able to corroborate their Carbon-14 results with complementary immunohistochemical techniques. In particular, they found: (i) a population of striatal interneurons that co-expresses immature neuronal markers; and (ii) the presence of IdU-labeled cells (i.e., recently born cells) that co-express neuronal markers in the striatum. Together, these findings corroborate the Carbon-14 dating results and strongly point toward the generation of new neurons in the human adult striatum.
As the authors of this paper admit, it is difficult to speculate on the role of these new interneurons at this time. This is in part due to the fact that the role of striatal calretinin-expressing interneurons is essentially unknown because this population of interneurons has not been studied in detail. This study by Ernst et al. will certainly increase interest in this particular type of striatal neuron and I predict that we will know more about their function in the near future. Nevertheless, the fact that new interneurons are being generated in the adult human striatum raises the possibility of using this intrinsic neurogenic capacity to develop neuronal replacement strategies for the treatment of diseases where striatal neuronal populations are depleted.
At this moment it is not clear whether the lack of generation of new interneurons in the striatum in Huntington's disease (HD) may contribute in some way to the pathogenesis of HD or whether it is a simple by-product of the degenerative process that occurs in this brain region during the course of the disease. Although this population of interneurons is not particularly affected in HD, which primarily targets medium spiny projection neurons, it certainly depends on the synaptic connections and neurochemical signals that it receives from the latter. Thus, it is reasonable to speculate that once medium spiny projection neurons are gone as a result of the HD degenerative process, the remaining neuronal populations are also affected. Within this scenario, even if immature interneurons migrate from the subventricular zone into the striatum in the HD brain, the lack of proper input from adjacent medium spiny projection neurons may hinder their final maturation and integration in the existing circuitry. Ultimately, this will contribute to the overall striatal dysfunction observed in HD.
Going forward, it will be important to clarify the function of these postnatal-born striatal interneurons. Questions to address in future studies include: (1) do these new interneurons become functionally integrated into the existing striatal circuitry (i.e., do they establish functional synapses with other striatal neurons)? And (2) are they functionally distinct from striatal interneurons that were born during development? These are complex questions to address in humans and it may be necessary to use cellular- and/or animal-based models to tackle these issues. Additionally, it will be important to further explore the role that interneurons play in the neuropathology of HD. Again, using animal models (such as some of the available HD transgenic mouse lines) might help with providing some insight into this issue.
References:
Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH.
Neurogenesis in the adult human hippocampus.
Nat Med. 1998 Nov;4(11):1313-7.
PubMed.
Comments
Island Medical Program, University of British Columbia AND Division of Medical Sciences, University of Victoria
It was well known that the human brain retains a certain degree of plasticity throughout postnatal and adult life. Adult hippocampal neurogenesis has been known to occur in the human brain since the pioneer study by Eriksson and colleagues (Eriksson et al., 1998), and neuroscientists speculate that the occurrence of neurogenesis in that brain region may be important in the role that the hippocampus plays in learning and memory. The study by Ernst et al. adds to this by showing the occurrence of postnatal neurogenesis in a different brain region, the striatum, thus illustrating that the human brain is indeed much more plastic than we had originally thought. That new neurons generated in the subventricular zone migrate not to the olfactory bulb (as they do in rodents), but rather to the adjacent striatum, where they differentiate into a particular neuronal population (interneurons) is surprising. This is a very exciting finding as it opens new avenues for the development of potential restorative therapeutic approaches that can utilize the endogenous neurogenic capacity of the brain to replace damaged or degenerating neurons within this brain region.
I was very convinced by the detailed analysis the authors performed in this study using the Carbon-14 dating technique. Further to that, they were able to corroborate their Carbon-14 results with complementary immunohistochemical techniques. In particular, they found: (i) a population of striatal interneurons that co-expresses immature neuronal markers; and (ii) the presence of IdU-labeled cells (i.e., recently born cells) that co-express neuronal markers in the striatum. Together, these findings corroborate the Carbon-14 dating results and strongly point toward the generation of new neurons in the human adult striatum.
As the authors of this paper admit, it is difficult to speculate on the role of these new interneurons at this time. This is in part due to the fact that the role of striatal calretinin-expressing interneurons is essentially unknown because this population of interneurons has not been studied in detail. This study by Ernst et al. will certainly increase interest in this particular type of striatal neuron and I predict that we will know more about their function in the near future. Nevertheless, the fact that new interneurons are being generated in the adult human striatum raises the possibility of using this intrinsic neurogenic capacity to develop neuronal replacement strategies for the treatment of diseases where striatal neuronal populations are depleted.
At this moment it is not clear whether the lack of generation of new interneurons in the striatum in Huntington's disease (HD) may contribute in some way to the pathogenesis of HD or whether it is a simple by-product of the degenerative process that occurs in this brain region during the course of the disease. Although this population of interneurons is not particularly affected in HD, which primarily targets medium spiny projection neurons, it certainly depends on the synaptic connections and neurochemical signals that it receives from the latter. Thus, it is reasonable to speculate that once medium spiny projection neurons are gone as a result of the HD degenerative process, the remaining neuronal populations are also affected. Within this scenario, even if immature interneurons migrate from the subventricular zone into the striatum in the HD brain, the lack of proper input from adjacent medium spiny projection neurons may hinder their final maturation and integration in the existing circuitry. Ultimately, this will contribute to the overall striatal dysfunction observed in HD.
Going forward, it will be important to clarify the function of these postnatal-born striatal interneurons. Questions to address in future studies include: (1) do these new interneurons become functionally integrated into the existing striatal circuitry (i.e., do they establish functional synapses with other striatal neurons)? And (2) are they functionally distinct from striatal interneurons that were born during development? These are complex questions to address in humans and it may be necessary to use cellular- and/or animal-based models to tackle these issues. Additionally, it will be important to further explore the role that interneurons play in the neuropathology of HD. Again, using animal models (such as some of the available HD transgenic mouse lines) might help with providing some insight into this issue.
References:
Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH. Neurogenesis in the adult human hippocampus. Nat Med. 1998 Nov;4(11):1313-7. PubMed.
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