Alterations to neuronal polarity following permanent axotomy: A quantitative analysis of changes to MAP2a/b and GAP‐43 distributions in axotomized motoneurons in the adult cat

Abstract

Following axotomy, morphologically unusual, distal processes (UDPs) emerge from motoneuron dendrites. These processes contain an axonal protein, growth-associated protein 43 (GAP-43) but lack immunostaining for the dendritic protein microtubule-associated protein 2a/b (MAP2a/b). Thus, it appears that neuronal polarity alters following axotomy. Our goal was to describe this change in neuronal polarity on a more detailed and quantitative level. We asked two questions: Following axotomy, where in the entire neuron does the immunoreactivity for MAP2a/b and GAP-43 change and do these changes reflect a transformation of dendrite to axon or growth from terminal dendrites? Using intracellular labeling and immunocytochemistry, changes in MAP2a/b and GAP-43 immunoreactivity were also found in processes with a morphology typical of terminal branches of intact motoneurons (called simple distal processes [SDPs]), as well as UDPs. Trajectories (the path from the soma to a single terminus) with UDPs and SDPs were longer than trajectories without these processes, and trajectories with UDPs were the longest. Trajectories without UDPs or SDPs were similar in length to trajectories from intact motoneurons. The distance from the soma to the point where MAP2a/b immunoreactivity became absent in trajectories with UDPs or SDPs was similar to the length of trajectories from intact motoneurons. Thus, following axotomy, two morphologically distinct types of axon-like processes emerge from dendrites. The formation of these processes does not involve a transformation of the original dendrite, but rather growth at the ends of dendrites.

Global Up-Regulation of Microtubule Dynamics and Polarity Reversal during Regeneration of an Axon from a Dendrite

“…Subsequent analysis showed that at the ultrastructural level the new processes emerging from dendrites after axon removal had axonal features, for example, abundant neurofilaments (Hall et al , 1989). Similar observations of growth of axon-like processes from dendrites in vivo have been made in cat motoneurons and interneurons after proximal axotomy (Rose et al , 2001; MacDermid et al , 2002; Fenrich et al , 2007), as well as several types of rodent neurons (Cho and So, 1992; Hoang et al , 2005). Axon removal experiments have also been performed in cultured neurons.…”

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

“…At post-axotomy intervals of Ͻ12 weeks, all ALPs emerge from the tips of distal dendrites (MacDermid et al, 2002). This suggests that dendrites giving rise to ALPs lose their dendritic identity over the course of ϳ20 weeks and are transformed into the proximal segments of the new axon.…”

“…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).…”

“…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).…”

“…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.…”