Isolation rearing impairs wound healing and is associated with increased locomotion and decreased immediate early gene expression in the medial prefrontal cortex of juvenile rats

Abstract

In addition to its maladaptive effects on psychiatric function, psychosocial deprivation impairs recovery from physical illness. Previously, we found that psychosocial deprivation, modeled by isolation rearing, depressed immediate early gene (IEG) expression in the medial prefrontal cortex (mPFC) and increased locomotion in the open field test (Levine, Youngs et al. 2007). In the present study, we examined whether similar changes in behavior and gene expression are associated with the maladaptive effects of psychosocial deprivation on physical injury healing. After weaning, anesthetized rats were subjected to a 20% total body surface area third degree burn injury and were subsequently either group or isolation reared. After four weeks of either isolation or group rearing (a period that encompasses rodent childhood and early adolescence), rats were sacrificed, and their healing and gene expression in the mPFC were assessed. Locomotion in the open field test was examined at 3 weeks post burn injury. We found that: 1) gross wound healing was significantly impaired in isolation reared rats compared to group reared rats, 2) locomotion was increased and IEG expression was suppressed for isolation reared rats during burn injury healing, 3) the decreased activity in the open field and increased IEG expression was greater for burn injury healing group reared rats than for uninjured group reared rats, 4) the degree of hyperactivity and IEG suppression was relatively similar between isolation reared rats during burn injury compared to uninjured isolation reared rats, 5) behavioral hyperactivity to novelty (the open

Prenatal lipopolysaccharide disrupts maternal behavior, reduces nest odor preference in pups, and induces anxiety: Studies of F1 and F2 generations

“…In the open field test, only an increased locomotor frequency was observed in both the control and experimental rats subjected to isolation, with no effect of LPS treatment. In this respect individual housing of rodents has been shown to induce hyperactivity upon exposure to a novel environment (Einon et al, 1978;Gentsch et al, 1982;Levine et al, 2008), suggesting that individually-housed rats react more vigorously (higher number of crossings) to the environmental novelty.The lack of effects on rearing frequencies and immobility time here observed probably resulted of the high variability observed.…”

Isolation rearing significantly perturbs brain metabolism in the thalamus and hippocampus

“…Further in both humans and animals, over the last decade, a substantial body of literature has been developed on the neurobiological impact of early psychosocial deprivation on brain development (Comery et al, 1996;Heidbreder et al, 2000;Chugani et al, 2001;Lu et al, 2004;Teicher et al, 2004;Bianchi et al, 2006;Day-Wilson et al, 2006;Levine et al, 2007Levine et al, , 2008Schubert et al, 2009;Vitalo et al, 2009;Fabricius et al, 2010;van Harmelen et al, 2010;Han et al, 2011).…”

“…Having previously identified that IR rats had decreased immediate early gene (IEG) expression in the mPFC and hippocampus (Levine et al, 2007(Levine et al, , 2008Vitalo et al, 2009), we hypothesized that these regions would show decreased FDG uptake. This hypothesis was based on the fact that both PET FDG and IEG expression reflect changes in neural activity and several studies have now shown that brain imaging of neuronal activity correlates with IEG expression (Lu et al, 2004;Stark et al, 2006;Dodd et al, 2010), although IEG expression does reflect some forms of neuronal activity change that are not detected by PET imaging (Guzowski et al, 2006;Stark et al, 2006;Marrone et al, 2008;Dodd et al, 2010).…”

Effects of postweaning social and physical deprivation on locomotor activity patterns and explorative behavior in female CD‐1 mice

“…Similarly, postweaning social and physical deprivation has measurable effects on basic behavior in rodents, though evidence is less conclusive and partly contradictory: effects range from a decrease in general activity (Roy et al, 2001) to hyperactivity in mice (Iso et al, 2007;Van de Weerd et al, 1999;Voikar, Polus, Vasar, & Rauvala, 2005;Zhu et al, 2006) and rats (Heidbreder et al, 2000;Levine et al, 2008), from decreased (Joseph & Gallagher, 1980) or unchanged (Zhu et al, 2006) exploratory behavior in rats, mice (Chapillon, Manneche, Belzung, & Caston, 1999), and female gerbils (Starkey, Normington, & Bridges, 2007), to increased play behavior in rats (Panksepp, 1981). Social deprivation can also lead to increased anxiety in male gerbils (Polaschek, 2004;Starkey et al, 2007) and mice (Voikar et al, 2005;Wolfer et al, 2004), whereas physical deprivation in C57 BL/6 mice leads to decreased anxiety (Zhu et al, 2006).…”