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Adult striatal neurogenesis and psychiatry

Adult neurogenesis in the human striatum: possible implications for psychiatric disorders

Molecular Psychiatry volume 21, pages 446–447 (2016)Cite this article

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Neuroplasticity induced by adult neurogenesis may have important roles in the generation and treatment of psychiatric disorders; however, the extent and functional significance of this process in humans remain unknown. The generation of new neurons persists only in two neurogenic niches of the adult mammalian brain: the subventricular zone (SVZ) and the dentate gyrus of the hippocampus. Whereas the existence of adult hippocampal neurogenesis was demonstrated in many species, including rodents and humans, the extent of SVZ neurogenesis in humans remained unclear for a long time.1 In rodents, new neurons migrate extensively from the SVZ to the olfactory bulb (OB). In contrast, in humans the OBs are sharply involuted compared with rodents, with no ongoing neurogenesis after birth.1 Surprisingly, however, a recent radiocarbon-14 dating study demonstrated the occurrence of robust adult neurogenesis in the human brain.2 This result is of great importance, as it represents only the second region where adult neurogenesis was detected in humans. Interestingly, most of the newly generated striatal neurons belong to a subclass of calretinin (CR)-positive GABAergic interneurons, similar to both neurons generated in the adult striatum and OB in other species, like rats and rabbits.1 However, unlike adult neurogenesis in the OB that was extensively investigated especially in rodent models, neurogenesis in the striatum in postnatal (during the first 3–4 weeks after birth) and adult stages is still very poorly understood. Up to date, two populations of small ‘granule-cell'-like striatal GABAergic interneurons were reported to be generated in the SVZ or locally at postnatal and/or adult stages: CR-positive interneurons and CR-negative granule cells forming the Islands of Calleja (ICj).1 Important for estimating the translational relevance of postnatal/adult striatal neurogenesis is the fact that both cell populations show a significant increase in humans compared with rodents: whereas the proportion of striatal CR-positive interneurons jumps from about 0.5% in rodents (where they represent the smallest group of interneurons) to 10% in humans—representing there the largest subtype—also the ICj reach their maximal expansion in humans in comparison with other species.1 This evolution suggests an unexpected even increased role of adult striatal neurogenesis in humans compared with rodents. Moreover, it supports the translational importance of studying this process in rodent models.

The striatum has important roles in several main functions of the brain, especially in those regulated by the dopamine system. Striatal dysfunction is associated with major psychiatric disorders, such as schizophrenia. Despite the lack of data regarding the role of postnatal/adult striatal neurogenesis in humans, several factors shown to modulate SVZ and/or striatal neurogenesis in rodents have potential relevance for psychiatric diseases:

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

    D Inta, A Meyer-Lindenberg & P Gass

  2. Department of Psychiatry (UPK), University of Basel, Basel, Switzerland

    U E Lang & S Borgwardt

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  1. D Inta
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  2. U E Lang
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  3. S Borgwardt
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  4. A Meyer-Lindenberg
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Correspondence to D Inta.

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Inta, D., Lang, U., Borgwardt, S. et al. Adult neurogenesis in the human striatum: possible implications for psychiatric disorders. Mol Psychiatry 21, 446–447 (2016). https://doi.org/10.1038/mp.2016.8

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