Neurogenesis and stem cells in adult mammalian dorsal root ganglia

We read with interest the Feature Article by M.S. Rao (1999) on stem cells in the nervous system, an issue that has gained great importance over the last year (Hines et al., 2000; van de Kooy and Weiss, 2000). In particular, the repeated reports of neurogenesis in adult life (Momma et al., 2000; Rao, 1999) have changed our viewpoint on a classical biological milestone and have opened up an intriguing new perspective on the treatment of the damaged nervous system (Weissman, 2000). This new perspective can throw new light on an old and still controversial issue: the existence of neurogenesis in adult mammalian dorsal root ganglia (DRGs). In our opinion, this issue has not been given the attention it deserves by the scientific community (as well as the broader issue of adult neurogenesis in the peripheral nervous system: Filogamo, 1987; Giacobini-Robecchi et al., 1985). The first study to investigate agerelated changes in the number of DRG neurons in mammals (rat) was published by Hatai in 1902. Though this author concluded that the total number of DRG neurons remains approximately constant with age, data reported in his paper (that were obtained from four animals only) showed a clear increase in cell counts from one month to five month old rats. From then on, there has been an alternation of data for and against the existence of an age-related increase in the number of mammalian DRG neurons. From the 1950s to the 1980s, several studies showed an age-related increase in DRG neurons in the rabbit (Sosa and de Zorrilla, 1966), in the cat (Tessler et al., 1985), and in the rat (Cavanaugh, 1951; Devor and GovrinLippman, 1985; Devor et al., 1991). In the early 1990s, in contrast with these results, Coggeshall and co-workers, using a modern design-based counting method (the disector), provided data in favor of the absence of neurogenesis in adult rat DRGs (La Forte et al., 1991; Pover et al., 1994) ascribing previous contrasting results to the employment of biased counting methods. However, evidence supporting the existence of an age-related increase in DRG neurons in the rat has been provided again more recently by Cecchini et al. (1995), Ciaroni et al. (2000), and Popken and Farel (1997) who employed both traditional model-based and new design-based counting methods. Finally, a study reporting a decrease in the number of DRG neurons in the very old rat (30 months) has recently been published (Bergman and Ulfhake, 1998). What is particularly surprising and indicative of the present confusion on this issue is that the authors of this paper did not even mention the previous works reporting an age-related increase in the number of DRG neurons—they just discussed their data within the broad issue of neuron loss occurring during aging of the nervous system. In our opinion, considering the great scientific relevance of the existence of neurogenesis in DRGs of adult mammals, it is surprising that few research groups have addressed this issue thus far, and that the recently reported controversial results did not stimulate new studies and a lively debate within the scientific community. The scientific calm surrounding this issue is attributable, in our view, to the impossibility of properly understanding and explaining the occurrence of relevant neurogenesis in adult DRGs in the context of a scientific milieu that restricted adult neurogenesis in mammals to a very few, particular situations, such as the olfactory neuroepithelium (Graziadei and Monti-Graziadei, 1979). However, recent scientific advances on stem cell biology (Momma et al., 2000; Rao, 1999; van de Kooy and Weiss, 2000; Weissman, 2000) could open new ways for understanding and interpreting the age-related increase of DRG neurons in adult mammals, if this occurrence were confirmed by further experimental evidence that stands up to the criticisms reported so far (La Forte et al., 1991; Pover et al., 1994). Apart from the possibility that new neurons originate from a local reserve of restricted neural stem cells, it could even be supposed that stem cells come from blood circulation, a hypothesis that only a few years ago would have been unfathomable. Today, on the basis of the recent demonstration that hematopoietic stem cells can give rise to astrocytes (Eglitis and Mezey, 1987) and that sub-ventricular astrocytes are neural stem cells Dr. Geuna is a Researcher and a Lecturer of Anatomy, and Dr. Giacobini-Robecchi is the Associate Professor of Anatomy in the Department of Clinical and Biological Sciences at the University of Torino. Their chief areas of research regarding development, plasticity, and repair of the peripheral nervous system. Dr. Borrione is a clinical hematologist with a background in neurobiology. Dr. Fornaro holds a research fellowship in neurobiology from the Fondazione Cavalieri Ottolenghi (Torino). Presently, these authors are working together on a research program on neural stem cells. This work was supported by grants from the MURST (Ministero dell’Università e della Ricerca Scientifica e Tecnologica). *Correspondence to: S. Geuna, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Ospedale San Luigi, Regione Gonzole 10, 10043 Orbassano (TO), Italy. Fax: 139.011. 90.38. 639; E-mail: geuna@sluigi.unito. it THE ANATOMICAL RECORD (NEW ANAT.) 261:139–140, 2000