Changed Synaptic Plasticity in Neural Circuits of Depressive-Like and Escitalopram-Treated Rats

Abstract

Background:Although progress has been made in the detection and characterization of neural plasticity in depression, it has not been fully understood in individual synaptic changes in the neural circuits under chronic stress and antidepressant treatment.Methods:Using electron microscopy and Western-blot analyses, the present study quantitatively examined the changes in the Gray’s Type I synaptic ultrastructures and the expression of synapse-associated proteins in the key brain regions of rats’ depressive-related neural circuit after chronic unpredicted mild stress and/or escitalopram administration. Meanwhile, their depressive behaviors were also determined by several tests.Results:The Type I synapses underwent considerable remodeling after chronic unpredicted mild stress, which resulted in the changed width of the synaptic cleft, length of the active zone, postsynaptic density thickness, and/or synaptic curvature in the subregions of medial prefrontal cortex and hippocampus, as well as the basolateral amygdaloid nucleus of the amygdala, accompanied by changed expression of several synapse-associated proteins. Chronic escitalopram administration significantly changed the above alternations in the chronic unpredicted mild stress rats but had little effect on normal controls. Also, there was a positive correlation between the locomotor activity and the maximal synaptic postsynaptic density thickness in the stratum radiatum of the Cornu Ammonis 1 region and a negative correlation between the sucrose preference and the length of the active zone in the basolateral amygdaloid nucleus region in chronic unpredicted mild stress rats.Conclusion:These findings strongly indicate that chronic stress and escitalopram can alter synaptic plasticity in the neural circuits, and the remodeled synaptic ultrastructure was correlated with the rats’ depressive behaviors, suggesting a therapeutic target for further exploration.

Escitalopram attenuates β-amyloid-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway

“…We observed that escitalopram significantly enhanced dendritic outgrowth and increased dendritic spines in hippocampal neuron cultures exposed to Aβ 1-42 . Our previous study has reported that escitalopram rescued synaptic deficits in depressive-like rats [ 41 ]. Moreover, several studies have revealed that the disturbance of synaptic plasticity recovered when tau hyperphosphorylation was reversed pharmacologically or with genetic technology [ 39 , 40 ], consistent with our results.…”

Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala

“…Chronic administration of another SSRI (escitalopram) decreased the length of the active zone of synapses that was increased by CUMS. In addition, escitalopram was able to restore spinophilin levels that were decreased in BLA after CUMS ( Li et al., 2015 ).…”

Environmental enrichment induces behavioural disturbances in neuropeptide Y knockout mice

“…it was reduced, pointing to increased synaptic gain in the DGpl. The relationship between reduced synaptic cleft width and impairment of spatial memory appears counterintuitive, given the common association of increased synaptic cleft width and negative behavioural phenotypes 50 51 . However, it needs to be kept in mind that it depends on the brain area investigated, its network structure and the functions of the neurons involved whether increased synaptic transmission efficiency translates into beneficial or adverse behavioural effects.…”