Abstract
Extraocular motoneurons resist degeneration in diseases such as amyotrophic lateral sclerosis. The main objective of the present work was to characterize the presence of neurotrophins in extraocular motoneurons and muscles of the adult rat. We also compared these results with those obtained from other cranial motor systems, such as facial and hypoglossal, which indeed suffer neurodegeneration. Immunocytochemical analysis was used to describe the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in oculomotor, trochlear, abducens, facial, and hypoglossal nuclei of adult rats, and Western blots were used to describe the presence of neurotrophins in extraocular, facial (buccinator), and tongue muscles, which are innervated by the above-mentioned motoneurons. In brainstem samples, brain-derived neurotrophic factor was present both in extraocular and facial motoneuron somata, and to a lesser degree, in hypoglossal motoneurons. Neurotrophin-3 was present in extraocular motor nuclei, while facial and hypoglossal motoneurons were almost devoid of this protein. Finally, nerve growth factor was not present in the soma of any group of motoneurons, although it was present in dendrites of motoneurons located in the neuropil. Neuropil optical density levels were higher in extraocular motoneuron nuclei when compared with facial and hypoglossal nuclei. Neurotrophins could be originated in target muscles, since Western blot analyses revealed the presence of the three molecules in all sampled muscles, to a larger extent in extraocular muscles when compared with facial and tongue muscles. We suggest that the different neurotrophin availability could be related to the particular resistance of extraocular motoneurons to neurodegeneration.
Highlights
According to the trophic theory of neural connections enunciated by Purves (1990), neurons depend on target-derived trophic support to survive during development
The vast majority of extraocular motoneurons, located in any of the three oculomotor-related nuclei, were positive for brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3), as revealed by the presence of a diffuse staining in the cytoplasm of extraocular motoneurons (Figures 1A,F,K for BDNF, Figures 1C,H,M for NT-3)
The main objective of the present work was to reveal the expression pattern of neurotrophins in the oculomotor system of the adult rat, as well as to compare these results with those obtained from other brainstem motor systems, such as facial and hypoglossal
Summary
According to the trophic theory of neural connections enunciated by Purves (1990), neurons depend on target-derived trophic support to survive during development. Neurotrophins are key actors in the development and maintenance of adult phenotype (Mertz et al, 2000). These molecules are implicated in regulatory pathways that mediate immature neuron survival. Both pro-neurotrophins and their mature forms have physiological effects They participate in the control of neuron homeostasis by interacting with two different types of receptors. The interaction of neurotrophin dimers with Trk receptors leads to receptor dimerization, reciprocal phosphorylation of their intracellular tyrosine kinase domain, and the activation of several downstream mechanisms implicated in the regulation of the effects already explained above, including the maintenance of the adult phenotype (Davis-López de Carrizosa et al, 2009)
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