Exogenous brain-derived neurotrophic factor regulates the synaptic composition of axonally lesioned and normal adult rat motoneurons

• Published in: Neuroscience Vol. 100; no. 1; pp. 171 - 181
• Main Authors: Novikov, L.N, Novikova, L.N, Holmberg, P, Kellerth, J.-O
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.2000; Elsevier
• Subjects: Animals; avulsion; Axons - physiology; Axotomy; Biological and medical sciences; Brain-Derived Neurotrophic Factor - pharmacology; Cell Death - physiology; Female; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Microscopy, Electron; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Motor Neurons - drug effects; Motor Neurons - physiology; Motor Neurons - ultrastructure; neurotrophic factors; Presynaptic Terminals - drug effects; Presynaptic Terminals - physiology; Presynaptic Terminals - ultrastructure; Rats; Rats, Sprague-Dawley; Reference Values; spinal cord; Spinal Nerve Roots - injuries; synapse; Synapses - drug effects; Synapses - physiology; Synapses - ultrastructure; synaptic plasticity; synaptophysin; Time Factors; Vertebrates: nervous system and sense organs; Wounds and Injuries - pathology; Wounds and Injuries - physiopathology; synaptophysin; avulsion; EM, electron microscopy; MG, medial gastrocnemius; BDNF, brain-derived neurotrophic factor; PBS, phosphate-buffered saline; neurotrophic factors; SYN, synaptophysin; spinal cord; synapse; synaptic plasticity; Neurotrophic factor; Synaptophysin; Vertebrata; Spinal cord; Mammalia; Rat; Rodentia; Central nervous system; Synaptic plasticity; Motor neuron; Brain derived neurotrophic factor; Lesion
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/S0306-4522(00)00256-6

Brain-derived neurotrophic factor has previously been shown to promote survival and axonal regeneration in injured spinal motoneurons and, also, to modulate synaptic transmission and regulate the density of synaptic innervation in a variety of neurons. The present light and electron microscopic study demonstrates synaptotrophic effects of exogenously applied brain-derived neurotrophic factor on the synaptic composition of both normal and axonally lesioned adult rat spinal motoneurons. After L5–L6 ventral root avulsion, a massive loss of all types of boutons occurred on the somata of the lesioned motoneurons which persisted for at least 12 weeks postoperatively. We found that (i) intrathecal infusion of brain-derived neurotrophic factor during the first postoperative week did not prevent the synaptic detachment and activation of glial cells; (ii) prolonged treatment for four weeks restored synaptic covering and significantly reduced microglial reaction; (iii) the synaptotrophic effect remained significant for at least eight weeks after cessation of the treatment; (iv) brain-derived neurotrophic factor mainly supported F-type boutons with presumably inhibitory function, while it had little effect on S-type boutons associated with excitatory action; and (v) in normal unlesioned motoneurons, four weeks of treatment with brain-derived neurotrophic factor induced sprouting of F-type boutons, a loss of S-type boutons and motoneuron atrophy. The present data show that exogenous neurotrophins not only help to restore synaptic circuitry in axonally injured motoneurons, but also strongly influence the synaptic composition in normal motoneurons.