Original contributionChronic lithium treatment antagonizes glutamate-induced decrease of phosphorylated CREB in neurons via reducing protein phosphatase 1 and increasing MEK activities
Section snippets
Cell culture and treatments
Primary cultures of cerebellar granule neurons were prepared from 8-day-old Sprague–Dawley rat pups. Briefly, cerebella were chopped into segments of 400 μm, and the cells dissociated by trypsinization, treated with DNase and triturated before being plated onto poly-l-lysine-coated 60-mm culture dishes or 24-well plates. The plating media consisted of basal Eagle’s medium containing 10% fetal calf serum, 2-mM glutamine, 50 μg/ml gentamicin, and 25 mM KCl. Cytosine β-d-arabinoside (10 μM) was
Results
Exposure of rat cerebellar granule cultures after 8 days in vitro (DIV) to different concentrations of glutamate and for varying periods of time caused a time- and dose-dependent change in pCREB at Ser133. At 5 μM glutamate, pCREB levels were significantly increased at all time points tested but there was little or no effect on total CREB levels (Fig. 1A). Treatment with 50 μM glutamate caused a transient but insignificant increase in pCREB after 2 min of exposure. After 15, 30 and 60 min of
Discussion
Our results demonstrate that acute glutamate and chronic lithium treatment can modulate pCREB levels in cultures of cerebellar granule cells prepared from 8-day-old rats. pCREB levels can be increased by relatively low concentrations of glutamate in a time-dependent, neuroprotective manner. Conversely, pCREB levels are decreased by higher concentrations of glutamate that are neurotoxic and act through NMDA receptors. Acute lithium treatment has no apparent effect on the glutamate-induced loss
Acknowledgements
We thank Jessica Madert for her excellent technical assistance and Peter Leeds for his assistance in many aspects of manuscript preparation.
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2013, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Post mortem studies reported altered CREB levels in MDD subjects and different CREB levels between treated and untreated patients (Dowlatshahi et al., 1998, 1999; Laifenfeld et al., 2005; Uslaner et al., 2009). Furthermore, CREB1 seems to be involved in antidepressant (Golan et al., 2011; Hisaoka et al., 2008; Qi et al., 2008), mood stabilizer (Boer et al., 2007, 2008; Casu et al., 2007; Hammonds and Shim, 2009; Kopnisky et al., 2003; Liang et al., 2008; Mai et al., 2002; Mamdani et al., 2008) and antipsychotic mechanisms of action in vivo and in vitro (Lee et al., 2010; Yang et al., 2004). Interestingly, previous research indicates that the MAPK/CREB signal system may be involved in the molecular mechanism of depression (Drago et al., 2011; Qi et al., 2006).