Adult spinal cord neurogenesis: A regulator of nociception

Abstract

Adult spinal cord neurogenesis occurs at low, constant rate under normal conditions and can be amplified by pathologic conditions such as injury or disease. The immature neurons produced through adult neurogenesis have increased excitability and migrate preferentially to the superficial dorsal horn layers responsible for nociceptive signaling. Under normal conditions, this process may be responsible for maintaining a steady-state, but adaptable level of nociceptive sensitivity, thus representing an experience-dependent mechanism of regulation similar to other neurogenic niches. Under pathologic conditions, adult spinal cord neurogenesis is greatly amplified and may therefore account for the observed changes in general spinal cord excitability and nociceptive sensitivity. This mechanism also explains many types of chronic pain present in the absence of injury or disease, which may be the result of impaired neuronal differentiation due to a variety of genetic variations. This suggests the possibility of using promoters of neuronal differentiation for the long-term treatment of the causes of chronic pain, unlike current medication which is palliative and effective only for the duration of treatment. The presence of this spinal cord neurogenic niche may also lead to new approaches in spinal cord regeneration.

TDP-43 aggregation inside micronuclei reveals a potential mechanism for protein inclusion formation in ALS

“…Evidence that supports our in vitro observations as a model of a pathophysiological phenomenon, comes from the observation of micronuclei-like structures in samples from three ALS patients, which were absent in neurologically healthy patients. We focused our study in hippocampus and spinal cord because both present TDP-43 pathology in ALS 50 and have been described to have neurogenesis 51,52 . Our main interest was to search for micronuclei in neurons; however, we cannot discard the possibility that micronuclei-like structures are also present in other types of neural cells.…”

GABA excitatory actions in cerebrospinal-fluid contacting neurones of adult mouse spinal cord

“…Immature neurones in adult mammalian central nervous system (CNS) represent a potential reservoir of young cells that may be mobilized under physiological or pathological conditions, such as injury or disease (La Rosa et al, 2019). Immature neurones were generally thought to localize in the subgranular zone of the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles, but recent studies have suggested the presence of immature neurones on a large scale in other parts of the CNS as well, such as the spinal cord and the hindbrain (Rusanescu & Mao, 2014;Rusanescu, 2016). Specifically, an intriguing expression of immature neuronal markers has been shown in medullo-spinal CSF-cNs of adult rodents (Stoeckel et al, 2003b;Orts-Del'immagine et al, 2014;Kútna et al, 2014), but the functional significance of such immaturity was not yet known.…”

The Restorative Effect of Human Amniotic Fluid Stem Cells on Spinal Cord Injury

“…However, in some pathologic conditions, such as SCI, the endogenous neurogenesis increased, to some extent, to replace neural loss, yet this compensation was not satisfactory [30]. A great deal of research has revealed that the stem cells and neurotrophic factors increased neurogenesis and improved the functional behavior in the SCI [31]. Additionally, other studies showed that cell transplantation could replace the lost cells and rescue the functional deficits in the SCI; however, some of the transplanted cells died due to an undesirable microenvironment, glial scar, lack of trophic factor, and oxidative stress [32].…”