Phospho cAMP response element–binding protein 1 expression level and the ultrastructure of neuron and synapse in hippocampus of depression rats

Objective To explore the alterations of ultrastructure of neuron and synapse in rat hippocampus induced by the expression changes of phospho cAMP response element–binding protein 1(p–CREB1), and the effect of venlafaxine on the expression of p–CREB1 and relative neuronal and synaptic plasticity. Methods Fifty–four rats were randomly divided into 4 groups: normal group (n=12), depression model matched group (n=14), saline group (n=14), and venlafaxine medication group (n=14). Sucrose water consumption test and open field test were performed to observe the behavior of animals. To investigate the learning and memory ability, rats were tested by Morris water maze. The expression of p–CREB1 protein was detected by immunohistochemistry and the CREB1 mRNA was measured by RT–PCR. The ultrastructure of neuron and synapse were observed with electron microscope. Correlation analysis was used to measure the associations among the number of p–CREB1 positive cells, the parameters of Morris water maze and synaptic morphology. Results (1)The sucrose consumption in depression model matched group (7.4±1.0) ml/100 g and saline group (7.5±1.0) ml/100 g were significantly less than that in normal group (9.6±0.3) ml/100 g and medication group (9.4±0.8) ml/100 g, (F=17.851, P<0.01). Morris water maze showed that the escape latent period in depression model matched group (61.1±10.5) s and saline group (59.0±10.6) s were more than that in normal group (29.8±10.1) s and medication group ((35.0±8.5) s; F=30.559, P<0.01), which demonstrated the learning and memory ability of depression rats were decreased. (2)The positive cell number of p–CREB1 in the hippocampus of depression model matched group (21.07±5.99) and saline group (24.57±6.97) were lower than that in normal group (29.70±6.21) and medication group (41.50±11.95; F=16.497, P<0.01). (3) The CREB1 mRNA expression in the hippocampus of depression model matched group (0.58±0.47) and saline group (0.45±0.24) were less than that in normal group (1.03±0.89) and medication group (1.10±0.45; F=6.669, P<0.01). (4)There were pathologic alterations in the ultrastructure of neurons and synapses in the hippocampus of depression rats, which were improved by pharmacological intervention. (5) The number of p–CREB1 positive cells was related to the parameters of Morris water maze and synaptic morphology. Conclusion p–CREB1 expression is correlated with neuronal and synaptic plasticity, and venlafaxine may be effective through influencing the expression of p–CREB1 and neuronal and synaptic plasticity. Key words: Depressive disorder; Cyclic AMP response element–binding protein; Neuronal plasticity; Hippocampus