The peptidic antidepressant spadin interacts with prefrontal 5-HT(4) and mGluR(2) receptors in the control of serotonergic function.

This study investigates the mechanism of action of spadin, a putative fast-acting peptidic antidepressant (AD) and a functional blocker of the K(+) TREK-1 channel, in relation with the medial prefrontal cortex (mPFC)-dorsal raphé (DRN) serotonergic (5-HT) neurons connectivity. Spadin increased 5-HT neuron firing rate by 113%, an augmentation abolished after electrolytic lesion of the mPFC. Among the few receptor subtypes known to modulate TREK-1, the stimulation of 5-HT4 receptors and the blockade of mGluR2/3 ones both activated 5-HT impulse flow, effects also suppressed by mPFC lesion.

Stress-induced opening of the permeability transition pore in the dystrophin-deficient heart is attenuated by acute treatment with sildenafil.

Susceptibility of cardiomyocytes to stress-induced damage has been implicated in the development of cardiomyopathy in Duchenne muscular dystrophy, a disease caused by the lack of the cytoskeletal protein dystrophin in which heart failure is frequent. However, the factors underlying the disease progression are unclear and treatments are limited. Here, we tested the hypothesis of a greater susceptibility to the opening of the mitochondrial permeability transition pore (PTP) in hearts from young dystrophic (mdx) mice (before the development of overt cardiomyopathy) when subjected to a stress protocol and determined whether the prevention of a PTP opening is involved in the cardioprotective effect of sildenafil, which we have previously reported in mdx mice.

Increased expression and intramitochondrial translocation of cyclophilin-D associates with increased vulnerability of the permeability transition pore to stress-induced opening during compensated ventricular hypertrophy.

Opening of the permeability transition pore (PTP) of mitochondria is a critical permeation event that compromises cell viability and may constitute a factor that participates to the loss of cardiomyocytes in compromised hearts. Mitochondria from hearts with volume overload-induced compensated hypertrophy are more vulnerable to opening of the PTP opening in response to a Ca2+ stress. Several of the factors known to affect PTP opening, including respiratory function, membrane potential, the rate of mitochondrial Ca2+ uptake and endogenous levels of Ca2+ in the mitochondrial matrix, were not altered by volume overload.

Resistance to Ca2+-induced opening of the permeability transition pore differs in mitochondria from glycolytic and oxidative muscles.

This study determined whether susceptibility to opening of the permeability transition pore (PTP) varies according to muscle phenotype represented by the slow oxidative soleus (Sol) and superficial white gastrocnemius (WG). Threshold for Ca2+-induced mitochondrial Ca2+ release following PTP opening was determined with a novel approach using permeabilized ghost myofibers. Threshold values for PTP opening were approximately threefold higher in fibers from WG compared with those from Sol (124+/-47 vs.

Descending GABAergic projections to the mesencephalic locomotor region in the lamprey Petromyzon marinus.

The mesencephalic locomotor region (MLR) plays a significant role in the control of locomotion in all vertebrate species investigated. Forebrain neurons are likely to modulate MLR activity, but little is known about their inputs. Descending GABAergic projections to the MLR were identified by double-labeling neurons using Neurobiotin injected into the MLR combined with immunofluorescence against GABA.

Bimodal locomotion elicited by electrical stimulation of the midbrain in the salamander Notophthalmus viridescens.

The present experiments were designed to identify the mesencephalic locomotor region (MLR) in the salamander. An in vitro semi-intact preparation from a decerebrate adult salamander (Notophthalmus viridescens) was developed in which the locomotor activities were monitored from electromyographic and video recordings. The results show that the two locomotor modes exhibited by salamanders (i.

Nicotinic activation of reticulospinal cells involved in the control of swimming in lampreys.

In lampreys as in other vertebrates, brainstem centres play a key role in the initiation and control of locomotion. One such centre, the mesencephalic locomotor region (MLR), was identified physiologically at the mesopontine border. Descending inputs from the MLR are relayed by reticulospinal neurons in the pons and medulla, but the mechanisms by which this is carried out remain unknown.