Emergence of axons from distal dendrites of adult mammalian neurons following a permanent axotomy

Abstract

The distinctive features of axons and dendrites divide most neurons into two compartments. This polarity is fundamental to the ability of most neurons to integrate synaptic signals and transmit action potentials. It is not known, however, if the polarity of neurons in the adult mammalian nervous system is fixed or plastic. Following axotomy, some distal dendrites of neck motoneurons in the adult cat give rise to unusual processes that, at a light microscopic level, resemble axons (Rose, P.K. & Odlozinski, M., J. Comp. Neurol., 1998, 390, 392). The goal of the present experiments was to characterize these unusual processes using well-established ultrastructural and molecular criteria that differentiate dendrites and axons. These processes were immunoreactive for growth-associated protein-43 (GAP-43), a protein that is normally confined to axons. In contrast, immunoreactivity for a protein that is widely used as a marker for dendrites, microtubule-associated protein (MAP)-2a/b, could not be detected in the unusual distal arborizations. At the electron microscopic level, unusual distal processes contained dense collections of neurofilaments and were frequently myelinated. These molecular and structural characteristics are typical of axons and suggest that the polarity of adult neurons in the mammalian nervous system can be disrupted by axotomy. If this transformation in neuronal polarity is common to other types of neurons, axon-like processes emerging from distal dendrites may represent a mechanism for replacing connections lost due to injury. Alternatively, the connections formed by these axons may be aberrant and therefore maladaptive.

Untangling the role of tau in Alzheimer’s disease: A unifying hypothesis

“…Axonal damage was among the first identified features of LOAD pathology [34] and subsequent studies using axotomy models established a link between the loss of overall neuronal polarity and perisomatic axonal injury [222][223][224][225]. We propose that an interplay between predisposing factors such as axon injury or reduced mitochondrial function amplify axonal changes due to tau misprocessing, neuronal dedifferentiation and Aβ generation [226][227][228][229][230].…”

Dendrite-Derived Supernumerary Axons on Adult Axotomized Motor Neurons Possess Proteins That Are Essential for the Initiation and Propagation of Action Potentials and Synaptic Vesicle Release

“…There is considerable evidence that proximal axotomy may trigger a similar reorganization of neuronal polarity both in vitro (Bradke and Dotti, 2000;Gomis-Rüth et al, 2008) and in vivo (Lindå et al, 1985(Lindå et al, , 1992Havton and Kellerth, 1987;Rose and Odlozinski, 1998;Rose et al, 2001;MacDermid et al, 2002MacDermid et al, , 2004. This reorganization is manifested in the emergence of axon-like processes (ALPs) from the terminals of distal dendrites (Lindå et al, 1985(Lindå et al, , 1992Rose et al, 2001;MacDermid et al, 2002MacDermid et al, , 2004Gomis-Rüth et al, 2008).…”

“…Tissue sections containing thick branches of ALPs that did not taper and matched the staining characteristics of myelinated "dendrites" (indicated by the disappearance and reappearance of the process as it traveled through the section) (Cullheim and Kellerth, 1978;Rose and Odlozinski, 1998;Rose et al, 2001) were processed immunohistochemically with either the pan-sodium channel antibody or an antibody against Nav1.2. Other tissue sections that contained ALPs that gave off fine branches that arborized extensively and had structures resembling boutons were processed immunohistochemically for SV2 and/or synaptophysin.…”

“…With time, these ALPs become myelinated (Lindå et al, 1992;Rose et al, 2001) and develop fine right-angled branches with bouton-like swellings, and the dendrites that give rise to these ALPs undergo a process of apparent axonification (MacDermid et al, 2004). ALPs lack dendritic cytoskeletal proteins and initially express the axonal growth proteins (Rose et al, 2001;MacDermid et al, 2002MacDermid et al, , 2004. Thus, the ALPs meet some of the morphological and molecular criteria of axons; however, it is unknown whether they have the functional capacity of an axon.…”

“…This reorganization is manifested in the emergence of axon-like processes (ALPs) from the terminals of distal dendrites (Lindå et al, 1985(Lindå et al, , 1992Rose et al, 2001;MacDermid et al, 2002MacDermid et al, , 2004Gomis-Rüth et al, 2008). With time, these ALPs become myelinated (Lindå et al, 1992;Rose et al, 2001) and develop fine right-angled branches with bouton-like swellings, and the dendrites that give rise to these ALPs undergo a process of apparent axonification (MacDermid et al, 2004).…”