Effects of Chronic Social Isolation on Wistar Rat Behavior and Brain Plasticity Markers

Abstract

Chronic stress is a contributing risk factor in the development of psychiatric illnesses, including depressive disorders. The mechanisms of their psychopathology are multifaceted and include, besides others, alterations in the brain plasticity. Previously, we investigated the effects of chronic social stress in the limbic brain structures of Wistar rats (hippocampus, HIPPO, and prefrontal cortex, PFC) and found multiple characteristics that resembled alterations described in some clinical studies of depression. We extended our investigations and followed the behavior of stressed animals by the open field test (OFT) and forced swimming test (FST), and the expression and polysialylation of synaptic plasticity markers, neural cell adhesion molecule (NCAM) and L1, in the HIPPO and PFC. We also determined the adrenal gland mass and plasma corticosterone (CORT) as a terminal part of the hypothalamic-pituitary-adrenal axis activity. Our data indicated that stressed animals avoided the central zone in the OFT and displayed decreased swimming, but prolonged immobility in the FST. The animals exhibited marked hypertrophy of the adrenal gland cortex, in spite of decreased serum CORT. Simultaneously, the stressed animals exhibited an increase in NCAM mRNA expression in the HIPPO, but not in the PFC. The synaptosomal NCAM of the HIPPO was markedly polysialylated, while cortical PSA-NCAM was significantly decreased. The results showed that chronic social isolation of Wistar rats causes both anxiety-like and depression-like behavior. These alterations are parallel with molecular changes in the limbic brain, including diminished NCAM sialylation in the PFC. Together with our previous results, the current observations suggest that a chronic social isolation model may potentially be used to study molecular mechanisms that underlie depressive symptomatology.

Streptozotocin diabetic mice display depressive-like behavior and alterations in the structure, neurotransmission and plasticity of medial prefrontal cortex interneurons

“…The expression of PSA-NCAM is regulated by chronic stress in the hippocampus (Pham et al, 2003;Sandi et al, 2001), the amygdala (Cordero et al, 2005), the piriform cortex (Nacher et al, 2004) and other cerebral regions (see (Sandi, 2004), for review). Although a recent report from our laboratory has not found changes in the number of PSA-NCAM immunoreactive neurons in the mPFC after chronic stress (Gilabert-Juan et al, 2013), changes in the expression of PSA-NCAM in this region have been reported after chronic social isolation stress (Djordjevic et al, 2012a) or chronic treatment with antidepressants (Djordjevic et al, 2012b;Guirado et al, 2012;Sairanen et al, 2007;Varea et al, 2007a). Moreover, experiments depleting PSA from or altering the expression of this molecule in the mPFC have revealed profound alterations in the inhibitory circuits of this cortical region , 2008Guirado et al, 2014Guirado et al, , 2012.…”

Ecological validity of social interaction tests in rats and mice

“…The detailed description of other amicable behaviors can be found in Barnett . Importantly, single‐housing or even reducing the number of animals kept in one cage, can be a major stressor for the rats (but see Reference ); after such period of isolation they display increased motivation to engage in social behaviors…”

Effects of social isolation and re-socialization on cognition and ADAR1 (p110) expression in mice

“…Investigations on both humans (Grant, Hamer & Steptoe, 2009) and rodent models (Fone & Porkess, 2008) indicate that social isolation can lead to cognitive dysfunction (Yusufishaq & Rosenkranz, 2013). Many studies have explored the possible reasons that are responsible for social isolation stress-induced cognitive deficit, including the alterations of glutamate receptors (Araki et al, 2014; Meffre et al, 2012), neurotransmitters (Baarendse et al, 2013; Hellemans, Nobrega & Olmstead, 2005), ion channels (Quan et al, 2010), Neural cell adhesion molecule (Pereda-Pérez et al, 2013; Djordjevic et al, 2012), and the hypothalamo-pituitary-adrenal (HPA) axis (Sandstrom & Hart, 2005; Pisu et al, 2016; Haj-Mirzaian et al, 2016). However, detailed mechanism is still not clear.…”