SorCS2 is involved in promoting periodontitis‐induced depression‐like behaviour in mice

Abstract

BackgroundEmerging evidence supports the association between periodontitis and depression, although the mechanisms are unclear. This study investigated the role of SorCS2 in the pathogenesis of periodontitis‐induced depression.Materials and MethodsAn experimental periodontitis model was established using SorCS2 knockout mice and their wild‐type littermates, and depression‐like behaviour was evaluated. The expression of proBDNF signalling, neuronal activity, and glutamate‐associated signalling pathways were further measured by western blotting and immunofluorescence. In addition, neuroinflammatory status, astrocytic and microglial markers, and the expression of corticosterone‐related factors were measured by immunofluorescence, western blotting, and enzyme‐linked immunosorbent assays.ResultsSorCS2 deficiency alleviated periodontitis‐induced depression‐like behaviour in mice. Further results suggested that SorCS2 deficiency downregulated the expression of pro‐BDNF and glutamate signalling and restored neuronal activities in mice with periodontitis. Neuroinflammation in the mouse hippocampus was triggered by experimental periodontitis but was not affected by SorCS2 deficiency. The levels of corticosterone and the expression of glucocorticoid receptors were also not altered.ConclusionOur study, for the first time, reveals the critical role of SorCS2 in the pathogenesis of periodontitis‐induced depression. The underlying mechanism involves proBDNF and glutamate signalling in the hippocampus, providing a novel therapeutic target for periodontitis‐associated depression.

Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction

“…More recently, the revelation of the importance of astrocyte Ca 2+ signaling in the control of homeostasis in brain circuits and behavioral regulation has led to the suggestion that we can potentially exploit this system in the treatment of MDD [ 195 , 196 ]. Moreover, it is now well documented that neurons and astrocytes through gliotransmission may contribute to depression by influencing synaptic plasticity as well as energy metabolism [ 195 , 196 , 197 ].…”

“…More recently, the revelation of the importance of astrocyte Ca 2+ signaling in the control of homeostasis in brain circuits and behavioral regulation has led to the suggestion that we can potentially exploit this system in the treatment of MDD [ 195 , 196 ]. Moreover, it is now well documented that neurons and astrocytes through gliotransmission may contribute to depression by influencing synaptic plasticity as well as energy metabolism [ 195 , 196 , 197 ]. Thus, further understanding of astrocyte-neuron involvement in MDD pathology, including alterations of pyramidal neuron and mid-spiny neurons, as well as alterations of gliotransmitters between astrocytes and neurons, could provide novel targets for MDD [ 195 , 197 , 198 , 199 ].…”

“…Moreover, it is now well documented that neurons and astrocytes through gliotransmission may contribute to depression by influencing synaptic plasticity as well as energy metabolism [ 195 , 196 , 197 ]. Thus, further understanding of astrocyte-neuron involvement in MDD pathology, including alterations of pyramidal neuron and mid-spiny neurons, as well as alterations of gliotransmitters between astrocytes and neurons, could provide novel targets for MDD [ 195 , 197 , 198 , 199 ].…”