Disruptions in brain-derived neurotrophic factor (BDNF) expression are proposed to contribute the molecular pathogenesis of Rett syndrome (RTT), a severe neurological disorder caused by loss-of-function mutations methyl-CpG-binding protein-2 (MeCP2). Although MeCP2 is transcriptional regulator BDNF, it unknown how affect transynaptic BDNF signaling. Our findings demonstrate an early, abnormal neurosecretory phenotype MeCP2-deficient neurons characterized significant increases percentage...

The neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) is a cotransmitter of acetylcholine at the adrenomedullary synapse, where autonomic regulation hormone secretion occurs. We have previously reported that survival prolonged metabolic stress in mice requires PACAP-dependent biosynthesis and catecholamines (CAs). In present experiments, we show CA evoked by direct high-frequency stimulation splanchnic nerve abolished native adrenal slices from male PACAP-deficient...

Abstract Adrenal medullary chromaffin cells are a major peripheral output of the sympathetic nervous system. Catecholamine release from these is driven by synaptic excitation innervating splanchnic nerve. Acetylcholine has long been shown to be primary transmitter at splanchnic‐chromaffin synapse, acting through ionotropic nicotinic acetylcholine receptors elicit action potential‐dependent secretion cells. This cholinergic stimulation desensitize under sustained stimulation, yet...

1. Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was by oxidative amperometry cell membrane turnover voltage clamp capacitance measurements. 2. The sAPs evoked inward Na(+) Ca(2+) currents that statistically identical to those native potential waveforms. On average, a single secretory granule underwent fusion sAP stimulation. An equivalent amount of then quickly...

Neuroendocrine chromaffin cells selectively secrete a variety of transmitter molecules into the circulation as function sympathetic activation. Activity-dependent release species is controlled through regulation secretory fusion pore. Under tone, basal synaptic excitation drives to modest levels catecholamine restricted In contrast, elevated activity, experienced under stress, results in pore expansion evoke maximal and facilitate copackaged peptide transmitters. Therefore, key control point...

Neuroendocrine chromaffin cells of the adrenal medulla in rat receive excitatory synaptic input through anterior and posterior divisions sympathetic splanchnic nerve. Upon stimulation, releases catecholamines, epinephrine, norepinephrine into suprarenal vein for circulation throughout body. Under tone, catecholamine release is modest. However, upon activation sympathoadrenal stress reflex, increased firing, output increases dramatically. Moreover, specific stressors can preferentially...

Abstract The sympathetic nervous system modulates cardiac contractile and electrophysiological function contributes to adverse remodelling following myocardial infarction (MI). Axonal modulation therapy (AMT), directed at the chain, blocks efferent outflow heart is a strategy transiently controllably mitigate chronic MI‐associated sympatho‐excitation. In porcine models, we evaluated scalable AMT, paravertebral in blocking reflex‐mediated pacing‐induced sympatho‐excitation post‐MI. level of...

The sympathetic nervous system modulates cardiac function by controlling key parameters such as chronotropy and inotropy. Sympathetic control of ventricular occurs through extrinsic innervation arising from the stellate ganglia thoracic chain. In healthy heart, release norepinephrine (NE) results in positive modulation chronotropy, inotropy, dromotropy, significantly increasing output. However, setting myocardial infarction or injury, activation persists, contributing to heart failure risk...

Graphical Abstract figure legend HCN channels play an evolutionarily conserved pacemaker role in renal pelvic smooth muscle (RPSM) of lower and higher order mammals. The function hyperpolarization-activated cation (HCN) pacemakers remains controversial. Renal trigger contractions that expel waste from the kidney, have been localized to these tissues. To date, however, mechanisms underlying RPSM activity remain elusive. was investigated both (top left) (bottom mammalian models, which exhibit...

Evidence suggests that chromaffin cells employ separate mechanisms for evoked endocytosis and granule recycling when stimulated at basal (∼0.5 Hz) stress‐activated (∼15 rates. Previous studies have focused mainly on elucidating the cellular responsible membrane under conditions similar to state indicate a clathrin/dephosphin‐mediated retrieval via coated pits. However, mechanism internalisation stimulus intensity remains largely unexplored. We electrically in adrenal tissue slices...

Previous studies have shown that catecholamine secretion from the adrenal medulla plays a critical role in chronic intermittent hypoxia (CIH)-induced alterations cardiovascular function. In present study we examined cellular mechanisms associated with effects of CIH on chromaffin cell secretion. Experiments were performed adult male mice (C57/BL6) exposed to 1-4 days or normoxia. Perforated patch electrical capacitance recordings freshly prepared medullary slices permit separating...

AbstractThis study aims to demonstrate the responses of monocarboxylate transporter 1 (MCT1) immunoreactive cells transient global ischemia in rat hippocampus using confocal and electron microscopy. The MCT1 staining CA1 pyramidal sham-operated controls appeared evenly distributed. Most products were associated with cell surface; however, some intracellular reaction are also found. This pattern stain was not altered first three days after an ischemic episode. As neuronal demise progressed,...

Neural cell adhesion molecule (NCAM) plays several critical roles in neuron path-finding and intercellular communication during development. In the clinical setting, serum NCAM levels are altered both schizophrenic autistic patients. knockout mice have been shown to exhibit deficits neuronal functions including impaired hippocampal long term potentiation motor coordination. Recent studies null indicated that synaptic vesicle trafficking active zone targeting impaired, resulting periodic...

Adrenal neuroendocrine chromaffin cells receive excitatory synaptic input from the sympathetic nervous system and secrete hormones into peripheral circulation. Under basal tone, modest amounts of freely soluble catecholamine are selectively released through a restricted fusion pore formed between secretory granule plasma membrane. Upon activation sympathoadrenal stress reflex, elevated stimulation drives expansion, resulting in increased secretion facilitating release copackaged peptide...

Sympathetic control of regional cardiac function occurs through postganglionic innervation from stellate ganglia and thoracic sympathetic chain. Whereas norepinephrine (NE) is their primary neurotransmitter, neuropeptide Y (NPY) an abundant cotransmitter. NPY plays a vital role in homeostatic processes including angiogenesis, vasoconstriction, remodeling. Elevated stress, resulting increased NE release, has been implicated the pathogenesis several cardiovascular disorders hypertension,...

Abstract Rett syndrome (RTT) is a progressive developmental disorder resulting from loss‐of‐function mutations in the gene encoding methyl‐CpG‐binding protein 2 (MeCP2), transcription regulatory protein. The RTT phenotype complex and includes severe cardiorespiratory abnormalities, dysautonomia behavioral symptoms of elevated stress. These findings have been attributed to an apparent hyperactivity sympathetic nervous system due defects brainstem development; however, possibility that...