EFFECTS OF INCREASED OPPORTUNITY FOR PHYSICAL EXERCISE AND LEARNING EXPERIENCES ON RECOGNITION MEMORY AND BRAIN-DERIVED NEUROTROPHIC FACTOR LEVELS IN BRAIN AND SERUM OF RATS K. VEDOVELLI, a,b E. SILVEIRA, a,b E. VELHO, a,b L. STERTZ, b,c F. KAPCZINSKI, b,c N. SCHRÖDER a,b AND E. BROMBERG a,b * a Neurobiology and Developmental Biology Laboratory, Faculty of Bio- sciences, Pontificial Catholic University, Porto Alegre, RS, Brazil b National Institute for Translational Medicine (INCT-TM), Porto Alegre, RS, Brazil c Laboratory of Molecular Psychiatry, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil Abstract—Studies with animal models showed that cellular, structural, and behavioral changes induced by environmental enrichment are related to increased levels of brain-derived neurotrophic factor (BDNF) in the brain. These evidence sug- gest that BDNF could be an interesting biomarker of the effects of lifestyle on cognition and other behavioral param- eters in humans, mainly if the BDNF alterations in brain are accompanied by correspondent peripheral modifications, since human studies depend basically on the evaluation of this neurotrophin in serum or plasma. To test this hypothe- sis, we analyzed the effects of environmental enrichment on long-term memory for object recognition and on BDNF levels of hippocampus, frontal cortex, and serum of rats exposed to an experimental protocol that could be more easily translated to human intervention studies. Animals were maintained for 10 weeks in a social (standard laboratory conditions) or en- riched (increased opportunity for physical exercise and learning experiences) condition. In the 7th week, they were submitted to behavioral testing (open field and novel object memory task), and at the end of the 10th week, they were killed and BDNF levels were analyzed. Animals maintained in the enriched condition showed enhanced performance on the memory task in the absence of any significant alteration in central or peripheral BDNF levels. The results of this study are important to highlight the need to develop experimental protocols using animal models that more closely resemble the characteristics of studies with humans and motivate more investigations to determine the conditions under which BDNF could be a biomarker of the effects of environment enrichment. © 2011 Published by Elsevier Ltd on behalf of IBRO. Key words: BDNF, serum, hippocampus, frontal cortex, envi- ronmental enrichment, novel object recognition. An increasing body of evidence from animal models has shown that enriched environment, namely rearing condi- tions that provide an increased opportunity for physical exercise, learning experiences, and social interaction, can improve development and function of brain over the life- time (Van Praaga et al., 2000; Cooper, 2005; Zhu et al., 2006). Among the behavioral changes induced by environ- mental enrichment are improvement in motor function (Jo- hansson, 1996; Risedal et al., 2002), learning and memory (Duffy et al., 2001; Gomez-Pinilla and Vaynman, 2005; Rossi and Angelucci, 2006), as well as emotionally related behaviors (Zhu et al., 2006; Koh et al., 2007). Cellular alterations, such as increases in neurogenesis, synaptic density, and neuronal plasticity (Mora et al., 2007) have also been observed in animals housed in complex envi- ronments and seem to be related to improvement in be- havioral parameters (Pham et al., 2002; Gobbo and O’Mara, 2004). These changes in neural circuits have been associated with alterations in central neurotrophic factors, especially brain-derived neurotrophic factor (BDNF). It is well documented that the expression and levels of BDNF in brain are prone to environmentally in- duced changes (Falkenberg et al., 1992; Pietropaolo et al., 2004; Gelfo et al., 2010) and that increases in BDNF induced by enriched environment are associated with bet- ter performance in different behavioral tasks (Schneider et al., 2001; Ickes et al., 2000; Gomez-Pinilla and Vaynman, 2005; Hopkins and Bucci, 2010). The binding of BDNF to tyrosine receptor kinase B (TrKB) and p75 neurotrophin receptors (p75 NTR) (Kermani and Hempstead, 2007; Hallbook et al., 2006) activates biochemical cascades that can lead to cell proliferation, survival, and plasticity (Mattson et al., 2004; Sossin and Barker, 2007) and, at least in part, explain the effects of enriched housing con- ditions on brain and behavior. All these evidence suggest that BDNF would be an interesting biomarker of the effects of environmental en- richment on cognition and other behavioral parameters in humans. A great number of studies on psychiatric (Cunha et al., 2006; Kim et al., 2007; Molendijk et al., in press; Pillai et al., 2010) and neurodegenerative disease patients (Mattson et al., 2004; Laske et al., 2006, 2011; Scalzo et al., 2010; Angelucci et al., 2010) have shown alterations of *Correspondence to: E. Bromberg, Faculty of Biosciences, Pontifical Catholic University, Av. Ipiranga, 6681 Prédio 12C, Sala 340, 90619- 900 Porto Alegre, RS, Brazil. Tel: +55-51-33203545; fax: +55-51-33203612. E-mail address: Bromberg@pucrs.br (E. Bromberg). Abbreviations: BDNF, brain-derived neurotrophic factor; BSA, bovine serum albumin; LTM, long-term memory; NOR, novel object recogni- tion memory; OD, optical density; PBS, phosphate buffer solution; p75 NTR, p75 neurotrophin receptor; TrKB, tyrosine receptor kinase B. Neuroscience 199 (2011) 284 –291 0306-4522/11 $ - see front matter © 2011 Published by Elsevier Ltd on behalf of IBRO. doi:10.1016/j.neuroscience.2011.08.012 284