Int. J. Devl Neuroscience 29 (2011) 833–838 Contents lists available at SciVerse ScienceDirect International Journal of Developmental Neuroscience j our na l ho me p age: www.elsevier.com/locate/ijdevneu Treadmill training induces plasticity in spinal motoneurons and sciatic nerve after sensorimotor restriction during early postnatal period: New insights into the clinical approach for children with cerebral palsy Felipe Stigger a,b , Patrícia S. do Nascimento a,b , Márcio F. Dutra a,b , Gabriela K. Couto b , Jocemar Ilha a,b , Matilde Achaval a,b , Simone Marcuzzo a,b,∗ a Programa de Pós-Graduac ¸ ão em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, RS, Brazil b Laboratório de Histofisiologia Comparada, Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, RS, Brazil a r t i c l e i n f o Article history: Received 23 June 2011 Received in revised form 19 August 2011 Accepted 3 September 2011 Keywords: Sensorimotor restriction Developmental disuse Rat spinal motoneuron Cell body size Myelinated nerve fibers Treadmill training a b s t r a c t The aim of the present study was to investigate whether locomotor stimulation training could have bene- ficial effects on the morphometric alterations of spinal cord and sciatic nerve consequent to sensorimotor restriction (SR). Male Wistar rats were exposed to SR from postnatal day 2 (P2) to P28. Control and exper- imental rats underwent locomotor stimulation training in a treadmill for three weeks (from P31 to P52). The cross-sectional area (CSA) of spinal motoneurons innervating hind limb muscles was determined. Both fiber and axonal CSA of myelinated fibers were also assessed. The growth-related increase in CSA of motoneurons in the SR group was less than controls. After SR, the mean motoneuron soma size was reduced with an increase in the proportion of motoneurons with a soma size of between 0 and 800 m 2 . The changes in soma size of motoneurons were accompanied by a reduction in the mean fiber and axon CSA of sciatic nerve. The soma size of motoneurons was reestablished at the end of the training period reaching controls level. Our results suggest that SR during early postnatal life retards the growth-related increase in the cell body size of motoneurons in spinal cord and the development of sciatic nerve. Addi- tionally, three weeks of locomotor stimulation using a treadmill seems to have a beneficial effect on motoneurons’ soma size. © 2011 ISDN. Published by Elsevier Ltd. All rights reserved. 1. Introduction Different studies have shown that the neuromuscular system display great adaptive potential in response to decreased neuro- muscular activity (Lieber, 1986a,b; Marcuzzo et al., 2008; Stigger et al., 2011; Ilha et al., 2011). Most of these studies were focused on skeletal muscle but there is also convincing evidence that dis- use produces neural adaptations (Canu et al., 2009). At least, in early stages of development, the mechanical activity imposed on the muscle fiber seems to play an important role in the maturation Abbreviations: BDNF, brain-derived neurotrophic factor; CNS, central nervous system; CP, cerebral palsy; CSA, cross-sectional area; CT, control; IGF-I, insulin growth factor I; NT-3, neurotrophim 3; P2, postnatal day 2; P14, postnatal day 14; P21, postnatal day 21; P28, postnatal day 28; P31, postnatal day 31; P52, postnatal day 52; PB, phosphate buffer; ROI, region of interest; SR, sensorimotor restriction; TrCT, trained control; TrSR, trained sensorimotor restriction. ∗ Corresponding author at: Laboratório de Histofisiologia Comparada, Departa- mento de Ciências Morfológicas, ICBS, Universidade Federal do Rio Grande do Sul, Sarmento Leite, 500. CEP: 90050-170, Porto Alegre, RS, Brazil. Tel.: +55 51 33083624. E-mail addresses: simone.marcuzzo@ufrgs.br, fstigger@yahoo.com.br (S. Marcuzzo). of the innervations (Greensmith et al., 1998). In fact, Nagatomo et al. (2009), using a model of hind limb unloading, showed that the increase in soma size of alpha motoneurons during develop- ment is regulated by motor activity and could be inhibited by a decrease in such activity. Additionally, during development, the neural impulse activity can affect myelinization (Fields, 2005; Zalc and Fields, 2000). Cerebral palsy (CP) is considered to be a motor disorder result- ing from a primary lesion in central nervous system (CNS) leading to impaired motor control, neuromuscular disorder and inactiv- ity (Graham and Selber, 2003; Foran et al., 2005). Patients with CP exhibit both nerve and dorsal rootlet demyelization (Chen, 2000; Fukuhara et al., 2010) and although there is a lack of stud- ies, evidence shows that the muscle condition found in those patients is secondary to a pathological change in peripheral nerve (Chen, 2000). In order to enhance motor skills and muscle strength, a child with CP usually begins treatment soon after diagnosis (Damiano, 2006). Several studies using animal models of CP have attempted to clarify the mechanisms involved in functional recov- ery. However, the major problem in most of these models is that they do not present the characteristic motor deficits seen in CP. 0736-5748/$36.00 © 2011 ISDN. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijdevneu.2011.09.002