PE-22-28 Research

Mazella E, Mendyk AM, Accart B, Borsotto M, Heurteaux C, Bordet R et al.

Post-stroke depression is a common and debilitating consequence of stroke that significantly impacts functional recovery and quality of life. Identifying new biological markers and treatments is essential to enhance patient care. This study aimed to assess the relationship between serum levels of...

Du C, Chen L, Liu G, Yuan F, Zhang Z, Rong M et al.

Ticks transmit a variety of pathogens, including rickettsia and viruses, when they feed on blood, afflicting humans and other animals. Bioactive components acting on inflammation, coagulation, and the immune system were reported to facilitate ticks' ability to suck blood and transmit tick-borne d...

García G, Martínez-Rojas VA, Murbartián J

TREK-1 channels are expressed in small nociceptive dorsal root ganglion (DRG) neurons where they participate in acute inflammatory and neuropathic pain. However, the role of TREK-1 in persistent pain is not well understood. The aim of this study was to investigate the local peripheral and spinal ...

Ren K, Liu H, Guo B, Li R, Mao H, Xue Q et al.

Quercetin is a well-known plant flavonoid with neuroprotective properties. Earlier work suggested it may relieve psychiatric disorders, cognition deficits and memory dysfunction through anti-oxidant and/or radical scavenging mechanisms. In addition, quercetin modulated the physiological function ...

Daziano G, Blondeau N, Béraud-Dufour S, Abderrahmani A, Rovère C, Heurteaux C et al.

Deterioration of insulin secretion and pancreatic beta-cell mass by inflammatory attacks is one of the main pathophysiological features of type 2 diabetes (T2D). Therefore, preserving beta-cell mass and stimulating insulin secretion only in response to glucose for avoiding the hypoglycemia risks,...

García G, Méndez-Reséndiz KA, Oviedo N, Murbartián J

PKC and PKA phosphorylation inhibit TREK-1 channels downstream of Gs protein-coupled receptor activation in vitro. However, the role of phosphorylation of TREK-1 in neuropathic pain is unknown. The purpose of this study was to investigate whether altered TREK-1 channel function by PKA and PKC mod...

Ma R, Lewis A

TREK-1 channel activity is a critical regulator of neuronal, cardiac, and smooth muscle physiology and pathology. The antidepressant peptide, spadin, has been proposed to be a TREK-1-specific blocker. Here we sought to examine the mechanism of action underlying spadin inhibition of TREK-1 channel...

Rivas-Ramírez P, Reboreda A, Rueda-Ruzafa L, Herrera-Pérez S, Lamas JA

Bradykinin (BK), a hormone inducing pain and inflammation, is known to inhibit potassium M-currents (IM) and to increase the excitability of the superior cervical ganglion (SCG) neurons by activating the Ca2+-calmodulin pathway. M-current is also reduced by muscarinic agonists through the depleti...

Pietri M, Djillani A, Mazella J, Borsotto M, Heurteaux C

Post-stroke depression (PSD) is the most common mood disorder following stroke with high relevance for outcome and survival of patients. The TREK-1 channel represents a crucial target in the pathogenesis of stroke and depression. Spadin and its short analog mini-spadin were reported to display po...

Mazella J, Borsotto M, Heurteaux C

The molecular identification of sortilin, also called neurotensin receptor-3, from three different biochemical approaches already predicted the involvement of the protein in numerous biological and cellular functions. The first important observation was that sortilin is synthesized as a precursor...

Djillani A, Pietri M, Mazella J, Heurteaux C, Borsotto M

Depression is a devastating mood disorder and a leading cause of disability worldwide. Depression affects approximately one in five individuals in the world and represents heavy economic and social burdens. The neurobiological mechanisms of depression are not fully understood, but evidence highli...

Roulot M, Minelli A, Bortolomasi M, Maffioletti E, Gennarelli M, Borsotto M et al.

Sortilin-derived propeptide (PE) and its synthetic analog spadin show strong antidepressant activity in rodents and, therefore, could be used as a biomarker to evaluate the clinical efficacy of antidepressant treatments. The aim of this study was to determine whether electroconvulsive therapy (EC...

Qi X, Xu H, Wang L, Zhang Z

The animal model for depressive behavior due to chronic unpredicted mild stress (CUMS) is commonly used to evaluate antidepressant treatments. The CUMS model has faced some criticism because of the heterogeneity of behavioral effects. Spadin and SID1900 are TREK1 blockers with a quick antidepress...

Yin Z, He W, Li Y, Li D, Li H, Yang Y et al.

Quiescence of myometrium contractile activity allows uterine expansion to accommodate the growing fetus and prevents preterm labor particularly during excessive uterine stretch in multiple pregnancy. However, the mechanisms regulating uterine response to stretch are unclear. We tested the hypothe...

Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M et al.

Depression is a devastating mental disorder that affects 20% of the population worldwide. Despite their proven efficacy, antidepressants present a delayed onset of action and serious adverse effects. Seven years ago, we described spadin (PE 12-28) as a promising endogenous peptide with antidepres...

Hivelin C, Béraud-Dufour S, Devader C, Abderrahmani A, Moreno S, Moha Ou Maati H et al.

Inhibition of the potassium channels TREK-1 by spadin (SPA) is currently thought to be a promising therapeutic target for the treatment of depression. Since these channels are expressed in pancreatic β-cells, we investigated their role in the control of insulin secretion and glucose homeost...

Devader C, Roulot M, Moréno S, Minelli A, Bortolomasi M, Congiu C et al.

Despite intense research on mechanisms underlying the depressive pathophysiology, reliable biomarkers to assess antidepressant treatment response are still lacking. Since the sortilin-derived propeptide (PE) displays potent antidepressant activities and can be measured in the blood of rodents, we...

Hivelin C, Mazella J, Coppola T

In this work, we aimed to correlate the expression of sortilin with the production of sortilin-derived propeptide (PE) during adipocyte differentiation, insulin resistance and inflammation. We also investigated the effect of spadin, a shorter analogue of PE that exerts a potent antidepressant in ...

Ye D, Li Y, Zhang X, Guo F, Geng L, Zhang Q et al.

Current antidepressants often remain the inadequate efficacy for many depressive patients, which warrant the necessary endeavor to develop the new molecules and targets for treating depression. Recently, the two-pore domain potassium channel TREK1 has been implicated in mood regulation and TREK-1...

Borsotto M, Veyssiere J, Moha Ou Maati H, Devader C, Mazella J, Heurteaux C et al.

Depression is a disease that is particularly frequent, affecting up to 20% of the population in Western countries. The origins of this pathology involve multiple genes as well as environmental and developmental factors leading to a disorder that remains difficult to treat. Several therapies for d...