ORIGINAL PAPER Isolation Stress Exposure and Consumption of Palatable Diet During the Prepubertal Period Leads to Cellular Changes in the Hippocampus R. Krolow • C. Noschang • D. M. Arcego • L. F. Pettenuzzo • S. N. Weis • M. L. Marcolin • A. P. Huffell • C. S. Mota • C. Dalmaz Received: 10 September 2012 / Revised: 19 October 2012 / Accepted: 24 October 2012 / Published online: 7 November 2012 Ó Springer Science+Business Media New York 2012 Abstract Social isolation is one of the most potent stressors in the prepubertal period and may influence dis- ease susceptibility or resilience in adulthood. The gluco- corticoid response and, consequently, the adaptive response to stress involve important changes in mitochondrial functions and apoptotic signaling. Previous studies have shown that consumption of a palatable diet reduces some stress effects. Therefore, the aim of the present study was to investigate whether isolation stress in early life can lead to cellular alterations in the hippocampus. For this, we evaluated oxidative stress parameters, DNA breakage index, mitochondrial mass and potential, respiratory chain enzyme activities, apoptosis, and necrosis in the hippo- campus of juvenile male rats submitted or not to isolation stress during the pre-puberty period. We also verified whether consumption of a palatable diet during this period can modify stress effects. Results show that stress led to an oxidative imbalance, DNA breaks, increased the mito- chondrial potential and early apoptosis, and decreased the number of live and necrotic cells. In addition, the palatable diet increased glutathione peroxidase activity, high mito- chondrial potential and complex I–III activity in the hip- pocampus of juvenile rats. The administration of a palatable diet during the isolation period prevented the stress effects that caused the reduction in live cells and increased apoptosis. In conclusion, the stress experienced during the pre-pubertal period induced a hippocampal oxidative imbalance, DNA damage, mitochondrial dys- function, and increased apoptosis, while consumption of a palatable diet attenuated some of these effects of exposure, such as the reduction in live cells and increased apoptosis, besides favoring an increase in antioxidant enzymes activities. Keywords Hippocampus Á Palatable diet Á Isolation stress Á Apoptosis Á Mitochondria Á Oxidative stress Introduction The prepubertal period is a time of transition, sexual maturation, and enhanced brain architecture plasticity. In addition, this period is critical for the final maturation of circuits controlling energy homeostasis and stress respon- ses [1]. Exposure to stressors in this phase of life may influence disease susceptibility or resilience in adulthood [2]. One of the most potent stressors, during this period, is social isolation [3], which can lead to behavioral, ana- tomical and neurochemical changes that may also be present in adulthood, when these animals are compared to their socially-reared litter mates (socials) [4, 5]. The exposure to stressful events leads to an increased release of glucocorticoids (GCs) due to activation of the hypothalamo-pituitary adrenal (HPA) axis. Additionally, glucocorticoid receptors (GR) mediate the negative feed- back of GCs on the HPA axis following stress. These receptors are localized in distinct brain structures, includ- ing the hippocampus, prefrontal cortex and hypothalamus; however GRs are more abundant in the hippocampus, R. Krolow (&) Á C. Noschang Á D. M. Arcego Á L. F. Pettenuzzo Á S. N. Weis Á M. L. Marcolin Á A. P. Huffell Á C. S. Mota Á C. Dalmaz Departamento de Bioquı ´mica, Instituto de Cie ˆncias Ba ´sicas da Sau ´de, UFRGS, Ramiro Barcelos, 2600 (Anexo) Lab. 37, Porto Alegre, Rio Grande do Sul 90035-003, Brazil e-mail: krolowrachel@yahoo.com.br C. Dalmaz e-mail: carladalmaz@yahoo.com.br 123 Neurochem Res (2013) 38:262–272 DOI 10.1007/s11064-012-0915-x