Abstract
Migraine and major depression are debilitating disorders with high lifetime prevalence rates. Interestingly these disorders are highly comorbid and show significant heritability, suggesting shared pathophysiological mechanisms. Non-homeostatic function of ion channels and neuroinflammation may be common mechanisms underlying both disorders: The excitation-inhibition balance of microcircuits and their modulation by monoaminergic systems, which depend on the expression and function of membrane located K+, Na+, and Ca+2 channels, have been reported to be disturbed in both depression and migraine. Ion channels and energy supply to synapses not only change excitability of neurons but can also mediate the induction and maintenance of inflammatory signaling implicated in the pathophysiology of both disorders. In this respect, Pannexin-1 and P2X7 large-pore ion channel receptors can induce inflammasome formation that triggers release of pro-inflammatory mediators from the cell. Here, the role of ion channels involved in the regulation of excitation-inhibition balance, synaptic energy homeostasis as well as inflammatory signaling in migraine and depression will be reviewed.
Highlights
Migraine and depression are comorbid diseases (Amiri et al, 2019; Karsan and Goadsby, 2021)
Inhibition of adenosine triphosphate (ATP) release selectively from astrocytes by genetic knockout of inositol 1,4,5trisphosphate (IP3) receptor type 2 (IP3R2−/−) lead to increased behavioral despair and anhedonia (Cao et al, 2013) (Table 1). These findings suggest that increased ATP release from astrocytes in the hippocampus and prefrontal cortex (PFC) in response to stressors is an important mediator in developing adaptive responses to stress
Contrary to P2x7R KO mice, mice homozygous or heterozygous for hP2X7R-Gln460Arg allele displayed no change in depression-like behavior at basal conditions, but they showed increased depression- and anxiety-like behavior following social defeat stress (Metzger et al, 2017) (Table 1). These findings indicate that P2X7 receptor (P2X7R) polymorphism creates vulnerability to stress and depression and supports the involvement of gene X environment interactions in the development of mood disorders
Summary
Migraine and depression are comorbid diseases (Amiri et al, 2019; Karsan and Goadsby, 2021). In NAc, one of the major targets of VTA DA neurons, both HCN 2 expression and function [I(h)] were reduced in cholinergic interneurons (ChIN) in two different mice depression models, namely chronic social defeat stress and p11 knockout mice (Cheng et al, 2019) (Figure 4).
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