Extraocular Motor System Exhibits a Higher Expression of Neurotrophins When Compared with Other Brainstem Motor Systems

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.

Motoneuronal Spinal Circuits in Degenerative Motoneuron Disease

“…The motoneurons lacking recurrent collaterals would thus be resistant to this process because they presumably derive their trophic needs from other sources including the motoneurons themselves and the muscles they innervate. Consistent with this hypothesis, the disease-resistant extraocular muscles express higher levels of neurotrophins than other brainstem neurons that are sensitive to disease (Hernández et al, 2017;Silva-Hucha et al, 2017). Extraocular muscles also contain high levels of insulin-like growth factor (IGF) compared to other cranial or spinal motoneurons (Allodi et al, 2016).…”

Myosin heavy chains in extraocular muscle fibres: Distribution, regulation and function

“…188 The burst and step features of ocular motoneuron impulses are mediated by different synaptic inputs and are maintained by different neurotrophins retrogradely transported from their target muscle fibres. 186 Muscle fibres, 189 including EOM fibres 190 are rich in brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF). Following axotomy, ocular motoneurons shed most of their synapses, resulting in reduced firing rates, with position sensitivity and velocity sensitivity constants k and r dropping by about 50% within 4 weeks.…”

Neuroprotective Effect of Vascular Endothelial Growth Factor on Motoneurons of the Oculomotor System

“…Previous studies described the anterograde and retrograde transport of VEGF to neurons, the latter being crucial for maintaining the integrity and functionality of NMJs [ 82 , 171 ]. The importance of trophic supply to ocular motoneurons is also emphasized by the higher expression of BDNF, NGF, and NT-3 found in the EOMs, compared to the buccinator and tongue muscles, target muscles for facial and hypoglossal motoneurons, respectively [ 172 ], emphasizing the role of the retrograde pathway as a source of trophic factors.…”