Olfactory bulbectomized (OBX) mice exhibit depressive-like behaviors as assessed by the tail suspension test (TST) and the forced swim test (FST). Interestingly, chronic intraperitoneal administration (1 mg/kg/day) of nefiracetam (DM-9384), a prototype cognitive enhancer, significantly improved depressive-like behaviors as well as spatial reference memory assessed by Y-maze task. As previously reported (Moriguchi, S., Han, F., Nakagawasai, O., Tadano, T., Fukunaga, K., 2006. Decreased calcium/calmoculin-dependent protein kinase II and protein kinase C activities mediate impairment of hippocampal long-term potentiation in the olfactory bulbectomized mice. J. Neurochem. 97, 22-29), decreased activities of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) in the hippocampal CA1 region and amygdala were observed in OBX mice. Nefiracetam treatment (1 mg/kg/day) significantly elevated CaMKII but not ERK activities in the amygdala, prefrontal cortex and hippocampal CA1 regions. In addition, we found an elevation of cAMP response element-binding protein (CREB) phosphorylation in the amygdala and prefrontal cortex but not in the hippocampal CA1 region. Increased CREB phosphorylation was associated with activation of CaMKI and CaMKIV as well as CaMKII in these regions. Taken together, in addition to CaMKII, CaMKI and CaMKIV activation mediated by nefiracetam treatment might mediate CREB phosphorylation following chronic nefiracetam treatment, thereby eliciting an anti-depressive and cognition-enhancing effect on OBX mice.
"It has been demonstrated that depressive behavior is associated with the downregulation of the PLC/IP3 pathway (Dwivedi et al., 2005). Previous studies suggest that CaMKIIα is not only involved in the synthesis of BDNF (Chen et al., 2012; Yu et al., 2013) but is also modulated by chronic stress (Suenaga et al., 2006; Barbiero et al., 2007; Han et al., 2009). It has also been demonstrated that SKF83959 promotes both striatal and prefrontal BDNF expression through CaMKIIα activation (Rashid et al., 2007b; Hasbi et al., 2009; Perreault et al., 2013). "
"peractivity in the open field test was measured first one week after surgery . The hyperactivity of OBX animals in an open field test is a robust effect that has been shown in our lab alone already for more than 20 separate experiments . Also in mice this phenomena is robust and described often ( Possidente et al . , 1996 ; Zueger et al . , 2005 ; Han et al . , 2009 ) . A large number of studies in rat and mouse have shown that OBX induced hyperactivity is normalized after chronic treatment with antidepressants ( Otmakhova et al . , 1992 ; Cryan et al . , 1998 ; Breuer et al . , 2007 ; Jarosik et al . , 2007 ; Roche et al . , 2007 ) . As in humans , the antidepressant treatment is not acutely effec"
"Interestingly, OBX animals show sensitivity to antidepressant treatments only after repeated administration, similar to the human condition, a feature that increases the validity of this animal model (Mar et al., 2002; Wang et al., 2007). The OBX surgical procedure consistently induces depression-like behaviors in diverse behavioral tests (Song et al., 1996; Wang et al., 2007; Tasset et al., 2008; Han et al., 2009). However, a comparative analysis of various behavioral tests that measure emotionality in the same cohort of OBX animals remains to be conducted. "
[Show abstract][Hide abstract] ABSTRACT: Disturbances in olfactory circuitry have been associated with depression in humans. The removal of olfactory bulbs (OBX lesion) has been largely used as a model of depression-like behavior in the rat. However, quantitative neuronal rearrangements in key brain regions in this animal model have not been evaluated yet. Accordingly, we investigated changes in hippocampal plasticity as well as behavioral deficits in this animal model. OBX-induced behavioral deficits were studied in a battery of tests, namely the open field test (OFT), forced swim test (FST), and spatial memory disturbances in the Morris Water Maze (MWM). To characterize the neuronal remodelling, neuroanatomical rearrangements were investigated in the CA1 hippocampus and piriform cortex, brain regions receiving inputs from the olfactory bulbs and associated with emotional or olfactory processes. Additionally, cell proliferation and survival of newborn cells in the adult dentate gyrus (DG) of hippocampus were also determined. OBX induced hyperlocomotion and enhanced rearing and grooming in the OFT, increased immobility in the FST as well as required a longer time to find the hidden platform in the MWM. OBX also induced dendritic atrophy in the hippocampus and piriform cortex. In addition, cell proliferation was decreased while the survival remained unchanged in the DG of these animals. These various features are also observed in depressed subjects, adding further support to the validity and usefulness of this model to evaluate potential novel antidepressants.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.