PSA Depletion Induces the Differentiation of Immature Neurons in the Piriform Cortex of Adult Mice

Abstract

Immature neurons are maintained in cortical regions of the adult mammalian brain. In rodents, many of these immature neurons can be identified in the piriform cortex based on their high expression of early neuronal markers, such as doublecortin (DCX) and the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). This molecule plays critical roles in different neurodevelopmental events. Taking advantage of a DCX-CreERT2/Flox-EGFP reporter mice, we investigated the impact of targeted PSA enzymatic depletion in the piriform cortex on the fate of immature neurons. We report here that the removal of PSA accelerated the final development of immature neurons. This was revealed by a higher frequency of NeuN expression, an increase in the number of cells carrying an axon initial segment (AIS), and an increase in the number of dendrites and dendritic spines on the immature neurons. Taken together, our results demonstrated the crucial role of the PSA moiety in the protracted development of immature neurons residing outside of the neurogenic niches. More studies will be required to understand the intrinsic and extrinsic factors affecting PSA-NCAM expression to understand how the brain regulates the incorporation of these immature neurons to the established neuronal circuits of the adult brain.

Brain Plasticity in Humans and Model Systems: Advances, Challenges, and Future Directions

“…Is there an involvement of perineuronal nets or surrounding astrocytic processes [65,92]? A recent report in which the polysialic acid polymer of the PSA-NCAM was enzymatically removed showed an increased maturation of the cortical nng-Ins in the mouse piriform cortex [93]. These data showcase the importance of the pericellular microenvironment in the maturational process.…”

“…In addition, though sharing the same markers, some plastic cell pop remarkably vary in their amount and distribution depending on animal species among ma DCX and PSA-NCAM are often co-expressed in newly born/young neurons this reason, in the past, were commonly considered associated with striking as structural plasticity, such as adult neurogenesis and cell migration [127,128,132]. theless, it is now clear that they are also expressed by resident neurons (non-new erated, non-migrating cells) that are generated during embryonic development ( nng-INs in layer II of the cerebral cortex [12,16,65,69,93,[139][140][141]). In addition, D PSA-NCAM expression has been described in similar cell populations located in tical regions (both in white and grey matter), and it is far from clear whether t generated postnatally or not [69][70][71][142][143][144].…”

“…These neurons are generated prenatally and retain the expression profiles of markers indicative of immaturity (see above). These neurons can progressively mature through the lifespan and integrate as functional neurons in the layer II of the cerebral cortex, namely, a brain region that is not endowed with stem cell-driven neurogenesis [65][66][67]93]. In this case, a whole cell retaining immature features is surrounded by a neuropil composed of mature neurons.…”

The PSA-NCAM-Positive “Immature” Neurons: An Old Discovery Providing New Vistas on Brain Structural Plasticity

“…How does the low level of neuronal production yield a dense population of immature marker-expressing neurons? To address this question, the following facts should be noted: (i) the period of immature state/maturation of newly generated neurons is much longer in non-human primates than in rodents, suggesting that a small number of proliferating progenitor cells can yield more immature neurons [120][121][122][123]; (ii) as we mentioned above, immature marker-expressing neurons occur in the adult brain of mammals (including nonhuman and human primates) independently of adult neurogenesis [46,49,78,82,93,[124][125][126];…”

“…PSA-NCAM, as a modulator of structural plasticity, can be involved in most of the abovementioned aspects. In a recent report, this molecule is important in the maturation process of mouse cortical immature neurons since the removal of PSA accelerates the final development of these cells [126]. Most importantly, since PSA-NCAM is considered to be a potential target to facilitate repair/regeneration after CNS injury and disease [129], its expression/modulation should be investigated in studies asking whether the immature neurons can be activated in experimental conditions and disease models.…”