Neurogenesis in the adult spinal cord in an experimental model of multiple sclerosis

Abstract

Multiple sclerosis is an inflammatory disease of the central nervous system characterized by inflammation, demyelination, axonal degeneration and accumulation of neurological disability. Previously, we demonstrated that stem cells constitute a possible endogenous source for remyelination. We now addressed the question of whether neurogenesis can occur in neuroinflammatory lesions. We demonstrated that, in experimental autoimmune encephalomyelitis, induced in rats 1,1'-dioctadecyl-6,6'-di(4sulphopentyl)-3,3,3',3'tetramethylindocarbocyanin(DiI)-labelled ependymal cells not only proliferated but descendants migrated to the area of neuroinflammation and differentiated into cells expressing the neuronal markers beta-III-tubulin and NeuN. Furthermore, these cells were immunoreactive for bromodeoxyuridine and PCNA, markers for cells undergoing cell proliferation. Using the whole-cell patch-clamp technique on freshly isolated 1, DiI-labelled cells from spinal cord lesions we demonstrated the ability of these cells to fire overshooting action potentials similar to those of immature neurones. We thus provide the first evidence for the initiation of neurogenesis in neuroinflammatory lesions in the adult spinal cord.

Neuronal differentiation of human mesenchymal stem cells: Changes in the expression of the Alzheimer's disease-related gene seladin-1

“…As a further clue supporting the hypothesis that seladin-1 is a predominant product of stem cells, we also detected a high amount of seladin-1 mRNA in the human adult hippocampus and spinal cord, which have been shown to contain neural stem cells with neurogenic activity [8][9][10] (Table 1). The level of seladin-1 mRNA in these regions was rather close to the amount of transcript detected in the adrenal cortex, one of the tissues in which the highest levels of transcription had been detected [1].…”

“…With regard to this point, it is worth mentioning that, according to the findings of Greeve et al [1], we detected high levels of seladin-1 transcript in the adult hippocampus, a well-known neurogenic brain region [8], and which is one of the areas affected in AD. Similarly, a high amount of seladin-1 mRNA was found in the spinal cord, in which stem cells with neurogenic properties have been recently described [9,10]. Alternatively, our findings might indicate a modification of the neurogenic properties of the adult brain as a consequence of neuronal damage and therefore of AD itself.…”

“…In fact, although neural stem cells are present in many other areas of the adult brain, they do not appear to maintain the ability to differentiate into neurons [8]. Very recently, stem cells with neurogenic activity have been described also in the adult spinal cord [9,10], which classically was not considered a neurogenic region [11]. Noteworthy, Greeve et al [1] detected the presence of rather high levels of expression of seladin-1 both in human normal hippocampus and spinal cord [1].…”

The Cannabinoid 1 Receptor and Progenitor Cells in the Adult Central Nervous System

“…This injured environment has been demonstrated as non-neurogenic (Yamamoto, Nagao et al 2001;Hannila, Siddiq et al 2007); however, there are instances in which an environment filled with inflammatory cytokines can still elicit neurogenesis in the adult spinal cord. For example, in an experimental rat model of multiple sclerosis (experimental autoimmune encephalomyelitis), newly generated neurons migrated towards the neuroinflammatory lesion (Danilov, Covacu et al 2006). Also there are instances of indirect injury to the adult spinal cord, such as dorsal rhizotomy (cutting of the dorsal root at the cervical spinal level) in which neurogenesis is observed in the dorsal horn at the corresponding spinal level (Vessal, Aycock et al 2007).…”

Adult spinal cord neurogenesis: A regulator of nociception

“…This idea has been reinforced by the observation that the proliferation of these adult stem cells is enhanced after injury or disease. [20][21][22][23][24] However, recent observations suggest that, in addition to the SGZ and the SVZ, adult neurogenesis is normally present on a large scale in other parts of the rodent CNS as well, for example in the spinal cord 25,26 and the hindbrain. 27 …”