Differential participation of CaMKII/ROCK and NOS pathways in the cholinergic inhibitory drive operated by nicotinic α7 receptors in perisynaptic Schwann cells.

Nicotinic α7 receptors (α7 nAChRs) present in perisynaptic Schwann cells (PSCs) control acetylcholine (ACh) spillover from the neuromuscular synapse by transiently increasing intracellular Ca, which fosters adenosine release via type 1 equilibrative nucleoside transporters (ENT1) and retrograde activation of presynaptic A inhibitory receptors. The putative Ca-dependent pathways downstream α7 nAChRs involved in the sensing inhibitory drive operated by PSCs is unknown. Herein, we used phrenic nerve-hemidiaphragm preparations from Wistar rats.

Mechanical stimulation-induced purinome priming fosters osteogenic differentiation and osteointegration of mesenchymal stem cells from the bone marrow of post-menopausal women.

Background: Mechanical stimulation (MS) significantly increases the release of adenine and uracil nucleotides from bone marrow-derived mesenchymal stem cells (BM-MSCs) undergoing osteogenic differentiation. Released nucleotides acting via ionotropic P2X7 and metabotropic P2Y purinoceptors sensitive to ATP and UDP, respectively, control the osteogenic commitment of BM-MSCs and, thus, bone growth and remodelling. Yet, this mechanism is impaired in post-menopausal (Pm)-derived BM-MSCs, mostly because NTPDase3 overexpression decreases the extracellular accumulation of nucleotides below the levels required to activate plasma membrane-bound P2 purinoceptors.

Silencing NTPDase3 activity rehabilitates the osteogenic commitment of post-menopausal stem cell bone progenitors.

Background: Endogenously released adenine and uracil nucleotides favour the osteogenic commitment of bone marrow-derived mesenchymal stromal cells (BM-MSCs) through the activation of ATP-sensitive P2X7 and UDP-sensitive P2Y receptors. Yet, these nucleotides have their osteogenic potential compromised in post-menopausal (Pm) women due to overexpression of nucleotide metabolizing enzymes, namely NTPDase3. This prompted us to investigate whether NTPDase3 gene silencing or inhibition of its enzymatic activity could rehabilitate the osteogenic potential of Pm BM-MSCs.

Purinergic Tuning of the Tripartite Neuromuscular Synapse.

The vertebrate neuromuscular junction (NMJ) is a specialised chemical synapse involved in the transmission of bioelectric signals between a motor neuron and a skeletal muscle fiber, leading to muscle contraction. Typically, the NMJ is a tripartite synapse comprising (a) a presynaptic region represented by the motor nerve ending, (b) a postsynaptic skeletal motor endplate area, and (c) perisynaptic Schwann cells (PSCs) that shield the motor nerve terminal. Increasing evidence points towards the role of PSCs in the maintenance and control of neuromuscular integrity, transmission, and plasticity.

Pitfalls and challenges of the purinergic signaling cascade in obesity.

Obesity is a worldwide health problem which have reached pandemic proportions, now also including low and middle-income countries. Excessive or abnormal fat deposition in the abdomen especially in the visceral compartment is tightly associated with a high metabolic risk for arterial hypertension, type II diabetes, cardiovascular diseases, musculoskeletal disorders (especially articular degeneration) and some cancers. Contrariwise, accumulation of fat in the subcutaneous compartment has been associated with a neutral metabolic impact, favoring a lower risk of insulin resistance.