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

Brain-derived neurotrophic factor has previously been shown to promote surv ival and axonal regeneration in injured spinal motoneurons and, also, to mo dulate synaptic transmission and regulate the density of synaptic innervati on in a variety of neurons. The present light and electron microscopic stud y 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 lesion ed motoneurons which persisted for at least 12 weeks postoperatively. We fo und that (i) intrathecal infusion of brain-derived neurotrophic factor duri ng the first postoperative week did not prevent the synaptic detachment and activation of glial cells; (ii) prolonged treatment for four weeks restore d synaptic covering and significantly reduced microglial reaction; (iii) th e synaptotrophic effect remained significant for at least eight weeks after cessation of the treatment; (iv) brain-derived neurotrophic factor mainly supported type boutons with presumably inhibitory function, while it had li ttle 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 b outons and motoneuron atrophy. The present data show that exogenous neurotrophins not only help to restore synaptic circuitry in axonally injured motoneurons, but also strongly infl uence the synaptic composition in normal motoneurons. (C) 2000 IBRO. Publis hed by Elsevier Science Ltd. All rights reserved.