Neurite Outgrowth Stimulated by Oxytocin Is Modulated by Inhibition of the Calcium Voltage-Gated Channels

Abstract

Neuropeptide oxytocin contributes to the regulation of the neuron differentiation and cell morphology. However, the precise mechanisms are not yet fully understood. Oxytocin receptor function and its coupling to calcium entry are obvious objects of interest in relation to the neuron morphology. Postsynaptic scaffolding proteins including SHANK proteins interact with other synaptic molecules and change dendritic morphology. SH-SY5Y neuroblastoma cell line represents a useful neurobiological in vitro model to study the short-term oxytocin effects on neurite outgrowth and underlying mechanisms. In the present study, we show that oxytocin induces an increase in the intracellular calcium in SH-SY5Y cells. Specificity of the calcium influx was verified by blockade of the oxytocin receptors with oxytocin receptor antagonist L-371,257. Neurite outgrowth stimulated by oxytocin was inhibited by specific voltage-gated calcium channel blockers. The exposure of SH-SY5Y cells to oxytocin resulted in a significant increase in the gene expression of SHANK1 and SHANK3 proteins. Overall, the present data indicate that oxytocin may contribute to the regulation of scaffolding proteins expression known to be associated with clusters of calcium channels at the cell membrane. It appears that oxytocin stimulated neurite outgrowth is, at least, in part dependent on the voltage-gated calcium channels.

Molecular Mechanisms of Oxytocin Signaling at the Synaptic Connection

“…It implies that oxytocin receptors can be related to the regulation of synapse scaffolding proteins. This conclusion is supported also by our results on the effects of oxytocin on the SHANK family of scaffolding proteins [ 47 ]. Higher dendritic complexity has been observed under the effect of oxytocin [ 70 ].…”

“…This concept suggests the existence of two-way communication between the presynaptic terminal and the postsynaptic synaptic membrane. Although in our study we did not distinguish between presynaptic/postsynaptic actions of oxytocin, we confirmed that oxytocin acts via a mechanism involving the N-type channels and P/Q-type channels inducing neurite outgrowth [ 47 ]. It is widely accepted that the presynaptic effect of oxytocin is dependent on extracellular calcium [ 48 ].…”

Neuronal morphology alterations in autism and possible role of oxytocin

“…In general, reorganization of the nervous tissue depends on various neuropeptides including oxytocin (Bakos et al 2016). Oxytocin can affect multiple molecular and cellular aspects of neuronal cells ranging from excitatory and inhibitory properties of synapses to rearrangement of the actin cytoskeleton (Leonzino et al 2016;Lestanova et al 2016;Zatkova et al 2018). We have demonstrated that oxytocin increases the expression of cytoskeletal proteins associated with neuronal growth (Lestanova et al 2016).…”

Abnormalities in interactions of Rho GTPases with scaffolding proteins contribute to neurodevelopmental disorders

“…Furthermore, it seems very likely that one of the factors that play a role in the pathogenesis of autism is the oxytocin receptor system, especially in early development. Oxytocin affects expression of neuron and glial markers in the brain (Havránek et al, ) and appears it could contribute to regulation of SHANK proteins as well (Zatkova et al, ). It has been suggested that oxytocin could be effective in the early treatment of neurodevelopmental diseases (Tauber et al, ).…”