Licenciada

6042 • The Journal of Neuroscience, May 6, 2009 • 29(18):6042– 6051

Development/Plasticity/Repair

Massage Accelerates Brain Development and the Maturation of Visual Function
Andrea Guzzetta,1 Sara Baldini,2 Ada Bancale,1 Laura Baroncelli,2 Francesca Ciucci,2 Paolo Ghirri,6 Elena Putignano,2 Alessandro Sale,2 Alessandro Viegi,2 Nicoletta Berardi,3,4 Antonio Boldrini,5 Giovanni Cioni,1,7 andLamberto Maffei2,3
Department of Developmental Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Stella Maris, I-56128 Calambrone, Pisa, Italy, 2Scuola Normale Superiore, I-56126 Pisa, Italy, 3Institute of Neuroscience of the Consiglio Nazionale delle Ricerche, I-56100 Pisa, Italy, 4Department of Psychology, Florence University, I-50121 Florence, Italy, 5Division of Neonatology,University of Pisa, I-56100 Pisa, Italy, 6Neonatology Unit, Section of Endocrinology and Dysmorphology, Azienda Ospedaliera Universitaria Pisa, I-56100 Pisa, Italy, and 7Division of Child Neurology and Psychiatry, University of Pisa, I56128 Calambrone, Pisa, Italy
1

Environmental enrichment (EE) was shown recently to accelerate brain development in rodents. Increased levels of maternal care,and particularly tactile stimulation through licking and grooming, may represent a key component in the early phases of EE. We hypothesized that enriching the environment in terms of body massage may thus accelerate brain development in infants. We explored the effects of body massage in preterm infants and found that massage accelerates the maturation of electroencephalographic activity and ofvisual function, in particular visual acuity. In massaged infants, we found higher levels of blood IGF-1. Massage accelerated the maturation of visual function also in rat pups and increased the level of IGF-1 in the cortex. Antagonizing IGF-1 action by means of systemic injections of the IGF-1 antagonist JB1 blocked the effects of massage in rat pups. These results demonstrate that massage has aninfluence on brain development and in particular on visual development and suggest that its effects are mediated by specific endogenous factors such as IGF-1.

Introduction
Environmental enrichment is a widely used paradigm for investigating the influence of sensory experience on brain and behavior. Enriched environment (EE) was first defined by Rosenzweig et al. (1978) as “a combination ofcomplex inanimate and social stimulation.” “Enriched” animals are reared in larger cages and in larger groups, and a variety of toys, tunnels, nesting material, and stairs are present and changed frequently. In addition, animals are typically given the opportunity for voluntary physical activity on running wheels. EE has remarkable effects on adult brain function in several species (van Praag et al.,2000; Nithianantharajah and Hannan, 2006; Sale et al., 2007). Recently, it has been shown that EE from birth leads to a conspicuous acceleration of visual system development in rodents, appreciable at the behavioral, electrophysiological, and molecular level (Cancedda et al., 2004; Landi et al., 2007). It has been suggested that, in the earliest phases of exposure to EE, the effects of EE do notstem from a direct action on the developing pups but rather from a variation in maternal behavior in enriched conditions (Cancedda et al., 2004; Sale et al., 2004). Indeed, it has been shown that pups in EE receive a higher level of
Received Nov. 19, 2008; revised Feb. 25, 2009; accepted Feb. 28, 2009. This work was supported by Ministero dell’Istruzione, dell’Universita, e della Ricerca (Progettidi Rilevante Inter` esse Nazionale) (L.M.) and Fondazione Mariani (G.C.). We thank Dr. Graziano Tinivella and Dr. Luc Zyw for their help with the statistical analysis. Technical help from Giulio Cappagli is gratefully acknowledged. Correspondence should be addressed to Prof. Lamberto Maffei, Institute of Neuroscience of the Consiglio Nazionale delle Ricerche, Via G. Moruzzi, 1, 56100 Pisa,...