Olfactory ensheathing glia: properties and function

Abstract

The failure of regenerating axons to grow within the adult mammalian central nervous system (CNS) does not apply to the olfactory bulb (OB). In this structure, normal and transected olfactory axons are able to enter, regenerate, and reestablish lost synaptic contacts with their targets, throughout the lifetime of the organism. A remarkable difference between an axonal growth-permissive structure such as the OB and the remaining CNS resides in the presence of ensheathing glia in the former. These cells exhibit phenotypic and functional properties known to be involved in the process of axonal elongation that may explain the permissibility of the OB to axonal growth. In addition, transplants of ensheathing glia were successfully used to promote axonal regeneration within the injured adult CNS. The axonal growth-promoting properties of ensheathing glia make the study of this cell type interesting to provide an insight into the mechanisms underlying the process of axonal regeneration. Therefore, in this article we review the developmental, morphologic, immunocytochemical, and functional properties presented by this unique glial cell type, and correlate them with the axonal growth-promoting ability of ensheathing glia. In addition, we provide some evidence of the potentiality that ensheathing glia might have as a promoter of axonal regeneration within the injured nervous system.

Introduction

The olfactory system of mammals has extensively been used to study the molecular and cellular bases of neurogenesis and axonal regeneration 3., 8., 16., 17., 20., 26., 31., 45., 92., 111., 141., 154.. Olfactory sensory neurons are located in the epithelium of the nasal cavity and project their axons to the central nervous system (CNS) where they synapse with dendrites of mitral, tufted, and periglomerular neurons in the glomeruli of the olfactory bulb (OB) 1., 56., 61., 74., 120.. The olfactory neuroepithelium has the extraordinary property of undergoing continuous turnover throughout the lifetime of the organism, and therefore, neurogenesis persists in the adult. Under normal conditions, the life span of olfactory neurons varies from 4–8 weeks depending on the species 20., 21., 26., 31., 45., 90., 92., 93., 108.. At all postnatal ages, olfactory neurons originate from precursor cells located in the deepest layer of the epithelium 15., 16., 20., 25., 31., 45., 63., 90., 92., 93., 104., 133., 141., 153.. Upon generation, neurons migrate apically in the epithelium and extend one apical dendrite and a basal axon. Newly formed axons are unmyelinated and form discrete bundles (fila olfactoria) that grow through the underlying basal cell layer, the connective tissue, and across the cribriform plate of the ethmoidal bone. These axons are able to traverse the pia mater, enter the CNS, and navigate within the olfactory nerve and glomerular layers of the OB, until they reach and synapse with target neurons 3., 26., 38., 62., 63.. Interestingly, neurogenesis and the ability of new olfactory neurons to extend their axons within the OB, persists after transection of the fila olfactoria or intranasal administration of neurotoxic drugs, at all postnatal ages. Under these circumstances, and similar to normal individuals, neuronal precursors give rise to neurons that grow their axons through the CNS until they reach their OB target neurons 17., 25., 31., 44., 57., 64., 65., 90., 104., 105., 106., 109., 111., 141., 154.. The permissivity of the OB to axonal elongation is surprising compared to other adult CNS regions where axonal regeneration after a damage is abortive 69., 80., 89., 121., 127.. The absence of axonal regeneration in the mature CNS has been attributed to the presence of an unfavorable glial environment surrounding the elongating axons 2., 13., 54., 69., 89., 112., 121., 131., 136., 138.. A remarkable difference between the OB and other regions of the adult CNS nonpermissive to axonal growth resides in their respective glial cell types. In addition to astrocytes, oligodendroglia and microglia, OBs contain ensheathing glia. This macroglial cell type is exclusively encountered in the OB layers where injured and uninjured regenerating olfactory axons navigate. In these layers, ensheathing glia enfold olfactory axons throughout their trajectory within the CNS, avoiding them to contact any other glial cell type 5., 12., 35., 36., 38., 39., 40., 56., 115., 119., 146.. The location, mode of association with axons, and phenotypic features displayed by ensheathing glia suggest a key role of this cell type in the regeneration of olfactory axons [125]. Moreover, these cells appeared to provide a useful tool to foster the elongation of damaged axons within nonregenerative adult CNS structures 86., 123., 126.. In this article, we review the specific properties of ensheathing glia reported so far, and provide some evidence of the potentiality of ensheathing glia in the treatment of CNS trauma.