Int. J. Devl Neuroscience 30 (2012) 363–367 Contents lists available at SciVerse ScienceDirect International Journal of Developmental Neuroscience j our na l ho me p age: www.elsevier.com/locate/ijdevneu Effects of enriched environment in spatial learning and memory of immature rats submitted to early undernourish and seizures Fabrício Simão, Juliana Antola Porto, Magda Lahorgue Nunes ∗ Neuroscience Laboratory, Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil a r t i c l e i n f o Article history: Received 12 January 2012 Received in revised form 11 April 2012 Accepted 11 April 2012 Keywords: Undernourishment Epilepsy Seizures Enriched environment Status epilepticus Visual-spatial memory a b s t r a c t We recently reported that early undernourishment and seizures to the rat brain resulted in morphological changes and progressive learning and memory disability, which started at around 6 week later and is representative of human adolescence. The purpose of the present study was to examine whether enriched environmental can recovery this slowly progressing deficits in early undernourished and in two different models for seizures. Undernourished groups were maintained on a nutritional deprivation regimen from post-natal day 2 (P2) to P15. From P8 to P10, recurrent seizures (RS) groups were exposed to three seizures per day, while status epilepticus (SE) groups experienced status epilepticus at P16, both induced by flurothyl. Next, animals were exposed to enriched environment between P30 and P60. Beginning at P61, all groups were trained and tested in the Morris water maze (MWM). Enriched environment led to a significant benefit in learning and retention of visual-spatial memory, being able to reverse the cognitive impairment generated by undernourishment and SE. © 2012 ISDN. Published by Elsevier Ltd. All rights reserved. 1. Introduction Undernourishment is responsible for serious physiological and morphological changes in the developing central nervous system (Huang et al., 2003). Structurally malnutrition results in tissue dam- age, growth retardation, disorderly differentiation, reduction in synapses and synaptic neurotransmitters, delayed myelination and reduced overall development of dendritic arborization of the devel- oping brain. There are deviations in the temporal sequences of brain maturation, which in turn disturb the formation of neuronal cir- cuits (Holmes and Ben-Ari, 2001). Long-term alterations in brain function have been reported which could be related to long lasting cognitive impairments associated with malnutrition (Levitsky and Strupp, 1995). Seizures in the developing brain might affect memory and cogni- tion (Liu et al., 2003; Lynch et al., 2000). As previously demonstrated in animal models, epilepsy and undernourishment are related, but a cause–effect relationship has not yet been established (Bronzino et al., 1997). Undernourishment does not seems to be a direct cause of epilepsy, however, several studies has reported a reduc- tion of seizures threshold in malnourished pup rats or adult rats ∗ Corresponding author at: Division of Neurology, Hospital São Lucas PUCRS, Av. Ipiranga 6690/220, 90610-000 Porto Alegre, RS, Brazil. Tel.: +55 51 33203318; fax: +55 51 33203316. E-mail address: nunes@pucrs.br (M.L. Nunes). (Florian and Nunes, 2011; Hemb et al., 2010; Palencia et al., 1996). While seizure-induced cell loss in the hippocampus may account for some of the cognitive impairment in patients with temporal lobe epilepsy (Pauli et al., 2006), there are indications that seizures may lead to functional impairment without necessarily causing cell loss. Environmental enrichment is defined as a combination of com- plex inanimate and social stimulation (Van Praag et al., 2000). It has been demonstrated to increase hippocampal synapse and spine density (Moser et al., 1994) and enhance long-term poten- tiation in the hippocampus, as well as improve spatial learning performance (Duffy et al., 2001; Van Praag et al., 2000). Benefi- cial effects of enriched environment following different types of seizures in the developing brain have been demonstrated by many authors such as improvement on cognition, enlargement of cerebral cortex, increased neurogenesis, increased dendritic sprouting, acti- vation of transcriptor factors and enhanced visuo-spatial memory (Rosenzweig and Bennett, 1996; Van Praag et al., 2000). While the immature brain appears to be less vulnerable to the adverse effects of prolonged seizures than the mature brain (Holmes et al., 2002), seizures early in life can be associated with later cognitive and behavioral disturbances, even in the absence of overt structural neuronal damage (Lynch et al., 2000; Stafstrom, 2002). The aim of this study was to verify the effects of environmen- tal enrichment on spatial learning and memory in rats submitted to early undernourishment, and two models of seizures: repeated early-life seizures and status epilepticus. 0736-5748/$36.00 © 2012 ISDN. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijdevneu.2012.04.002