scholarly journals Anesthetic Treatment Blocks Synaptogenesis But Not Neuronal Regeneration of Cultured Lymnaea Neurons

2003 ◽  
Vol 90 (4) ◽  
pp. 2232-2239 ◽  
Author(s):  
Alyson J. Woodall ◽  
Hiroaki Naruo ◽  
David J. Prince ◽  
Zhong Ping Feng ◽  
William Winlow ◽  
...  
Keyword(s):  
Nerve Regeneration ◽  
Acetylcholine Receptors ◽  
Direct Evidence ◽  
Molluscan Neurons ◽  
Synaptic Connections ◽  
Surgical Interventions ◽  
Cholinergic Synaptic Transmission ◽  
Lymnaea Neurons

Trauma and injury necessitate the use of various surgical interventions, yet such procedures themselves are invasive and often interrupt synaptic communications in the nervous system. Because anesthesia is required during surgery, it is important to determine whether long-term exposure of injured nervous tissue to anesthetics is detrimental to regeneration of neuronal processes and synaptic connections. In this study, using identified molluscan neurons, we provide direct evidence that the anesthetic propofol blocks cholinergic synaptic transmission between soma-soma paired Lymnaea neurons in a dose-dependent and reversible manner. These effects do not involve presynaptic secretory machinery, but rather postsynaptic acetylcholine receptors were affected by the anesthetic. Moreover, we discovered that long-term (18–24 h) anesthetic treatment of soma-soma paired neurons blocked synaptogenesis between these cells. However, after several hours of anesthetic washout, synapses developed between the neurons in a manner similar to that seen in vivo. Long-term anesthetic treatment of the identified neurons visceral dorsal 4 (VD4) and left pedal dorsal 1 (LPeD1) and the electrically coupled Pedal A cluster neurons (PeA) did not affect nerve regeneration in cell culture as the neurons continued to exhibit extensive neurite outgrowth. However, these sprouted neurons failed to develop chemical (VD4 and LPeD1) and electrical (PeA) synapses as observed in their control counterparts. After drug washout, appropriate synapses did reform between the cells, although this synaptogenesis required several days. Taken together, this study provides the first direct evidence that the clinically used anesthetic propofol does not affect nerve regeneration. However, the formation of both chemical and electrical synapses is severely compromised in the presence of this drug. This study emphasizes the importance of short-term anesthetic treatment, which may be critical for the restoration of synaptic connections between injured neurons.

scholarly journals Polymers for Fabricating Nerve Conduits

2010 ◽  
Vol 2010 ◽  
pp. 1-20 ◽  
Author(s):  
Shanfeng Wang ◽  
Lei Cai
Keyword(s):  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
Synthetic Polymers ◽  
Thermal And Mechanical Properties ◽  
Biological Functions ◽  
Intrinsic Properties ◽  
Polymeric Systems ◽  
Nerve Conduits

Peripheral nerve regeneration is a complicated and long-term medical challenge that requires suitable guides for bridging nerve injury gaps and restoring nerve functions. Many natural and synthetic polymers have been used to fabricate nerve conduits as well as luminal fillers for achieving desired nerve regenerative functions. It is important to understand the intrinsic properties of these polymers and techniques that have been used for fabricating nerve conduits. Previously extensive reviews have been focused on the biological functions and in vivo performance of polymeric nerve conduits. In this paper, we emphasize on the structures, thermal and mechanical properties of these naturally derived synthetic polymers, and their fabrication methods. These aspects are critical for the performance of fabricated nerve conduits. By learning from the existing candidates, we can advance the strategies for designing novel polymeric systems with better properties for nerve regeneration.

scholarly journals Beneficial Metabolic Effects Caused by Persistent Activation of β-Cell M3 Muscarinic Acetylcholine Receptors in Transgenic Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5185-5194 ◽  
Author(s):  
Dinesh Gautam ◽  
Inigo Ruiz de Azua ◽  
Jian Hua Li ◽  
Jean-Marc Guettier ◽  
Thomas Heard ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Transgenic Mice ◽  
Acetylcholine Receptors ◽  
Muscarinic Acetylcholine Receptors ◽  
Metabolic Effects ◽  
Β Cells ◽  
Β Cell ◽  
Muscarinic Acetylcholine

Previous studies have shown that β-cell M3 muscarinic acetylcholine receptors (M3Rs) play a key role in maintaining blood glucose homeostasis by enhancing glucose-dependent insulin release. In this study, we tested the hypothesis that long-term, persistent activation of β-cell M3Rs can improve glucose tolerance and ameliorate the metabolic deficits associated with the consumption of a high-fat diet. To achieve the selective and persistent activation of β-cell M3Rs in vivo, we generated transgenic mice that expressed the Q490L mutant M3R in their pancreatic β-cells (β-M3-Q490L Tg mice). The Q490L point mutation is known to render the M3R constitutively active. The metabolic phenotypes of the transgenic mice were examined in several in vitro and in vivo metabolic tests. In the presence of 15 mm glucose and the absence of M3R ligands, isolated perifused islets prepared from β-M3-Q490L Tg mice released considerably more insulin than wild-type control islets. This effect could be completely blocked by incubation of the transgenic islets with atropine (10 μm), an inverse muscarinic agonist, indicating that the Q490L mutant M3R exhibited ligand-independent signaling (constitutive activity) in mouse β-cells. In vivo studies showed that β-M3-Q490L Tg mice displayed greatly improved glucose tolerance and increased serum insulin levels as well as resistance to diet-induced glucose intolerance and hyperglycemia. These results suggest that chronic activation of β-cell M3Rs may represent a useful approach to boost insulin output in the long-term treatment of type 2 diabetes.

Light-dark dependence of electrocardiographic changes during asphyxia and reoxygenation in a rat model

Open Medicine ◽  
2010 ◽  
Vol 5 (5) ◽  
pp. 611-619
Author(s):  
Ivana Bačová ◽  
Pavol Švorc ◽  
Martin Kundrík ◽  
Benjamin Fulton
Keyword(s):  
Rat Model ◽  
Qt Interval ◽  
Pulmonary Ventilation ◽  
Time Intervals ◽  
Surgical Interventions ◽  
Qt Intervals ◽  
Female Wistar Rats ◽  
Electrocardiographic Changes

AbstractThe aim of this study was to evaluate the effect of ventilation on electrocardiographic time intervals as a function of the light-dark (LD) cycle in an in vivo rat model. RR, PQ, QT and QTc intervals were measured in female Wistar rats anaesthetized with both ketamine and xylazine (100 mg/15 mg/kg, i.m., open chest experiments) after adaptation to the LD cycle (12:12h) for 4 weeks. Electrocardiograms (ECG) were recorded before surgical interventions; after tracheotomy, and thoracotomy, and 5 minutes of stabilization with artificial ventilation; 30, 60, 90 and 120 seconds after the onset of apnoea; and after 5, 10, 15, and 20 minutes of artificial reoxygenation. Time intervals in intact animals showed significant LD differences, except in the QT interval. The initial significant (p<0,001) LD differences in PQ interval and loss of dependence on LD cycle in the QT interval were preserved during short-term apnoea-induced asphyxia (30–60 sec) In contrast, long-term asphyxia (90–120 sec) eliminated LD dependence in the PQ interval, but significant LD differences were shown in the QT interval. Apnoea completely abolished LD differences in the RR interval. Reoxygenation restored the PQ and QT intervals to the pre-asphyxic LD differences, but with the RR intervals, the LD differences were eliminated. We have concluded that myocardial vulnerability is dependent on the LD cycle and on changes of pulmonary ventilation.

scholarly journals Somatic nicotinic acetylcholine receptors control the activity of dopamine neurons and reward-related behaviors

2018 ◽  
Author(s):  
Romain Durand-de Cuttoli ◽  
Sarah Mondoloni ◽  
Fabio Marti ◽  
Damien Lemoine ◽  
Jérémie Naudé ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Direct Evidence ◽  
Dynamic Range ◽  
Dopamine Neurons ◽  
Optical Manipulation ◽  
Chemical Genetic ◽  
Brain Circuits ◽  
Firing Properties

SummaryDopamine (DA) neurons of the ventral tegmental area (VTA) integrate cholinergic inputs to regulate key functions such as motivation and goal-directed behaviors. Yet the temporal dynamic range and mechanism of action of acetylcholine (ACh) on the modulation of VTA circuits and reward-related behaviors are not known. Here we used a chemical-genetic approach for rapid and precise optical manipulation of nicotinic neurotransmission in VTA neurons in vivo. We provide direct evidence that the ACh tone fine-tunes the firing properties of VTA DA neurons through somatic β2-containing (β2*) nicotinic ACh receptors (nAChRs). Furthermore, locally photo-antagonizing these receptors in the VTA was sufficient to reversibly switch nicotine reinforcement on and off. By enabling control of nicotinic transmission in targeted brain circuits, this technology will help unravel the various physiological functions of nAChRs and may assist in the design of novel therapies relevant to neuropsychiatric disorders.

scholarly journals Cholinergic Nerve Differentiation of Mesenchymal Stem Cells Derived from Long-Term Cryopreserved Human Dental Pulp In Vitro and Analysis of Their Motor Nerve Regeneration Potential In Vivo

2018 ◽  
Vol 19 (8) ◽  
pp. 2434 ◽  
Author(s):  
Soomi Jang ◽  
Young-Hoon Kang ◽  
Imran Ullah ◽  
Sharath Shivakumar ◽  
Gyu-Jin Rho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nerve Regeneration ◽  
Dental Pulp ◽  
Motor Nerve ◽  
Cholinergic Neurons ◽  
Human Dental Pulp

The reduction of choline acetyltransferase, caused by the loss of cholinergic neurons, leads to the absence of acetylcholine (Ach), which is related to motor nerve degeneration. The aims of the present study were to evaluate the in vitro cholinergic nerve differentiation potential of mesenchymal stem cells from cryopreserved human dental pulp (hDPSCs-cryo) and to analyze the scale of in vivo motor nerve regeneration. The hDPSCs-cryo were isolated and cultured from cryopreserved dental pulp tissues, and thereafter differentiated into cholinergic neurons using tricyclodecane-9-yl-xanthogenate (D609). Differentiated cholinergic neurons (DF-chN) were transplanted into rats to address sciatic nerve defects, and the scale of in vivo motor nerve regeneration was analyzed. During in vitro differentiation, the cells showed neuron-like morphological changes including axonal fibers and neuron body development, and revealed high expression of cholinergic neuron-specific markers at both the messenger RNA (mRNA) and protein levels. Importantly, DF-chN showed significant Ach secretion ability. At eight weeks after DF-chN transplantation in rats with sciatic nerve defects, notably increased behavioral activities were detected with an open-field test, with enhanced low-affinity nerve growth factor receptor (p75NGFR) expression detected using immunohistochemistry. These results demonstrate that stem cells from cryopreserved dental pulp can successfully differentiate into cholinergic neurons in vitro and enhance motor nerve regeneration when transplanted in vivo. Additionally, this study suggests that long-term preservation of dental pulp tissue is worthwhile for use as an autologous cell resource in the field of nerve regeneration, including cholinergic nerves.

scholarly journals Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus timing-dependent plasticity in fusiform cells of the dorsal cochlear nucleus

2017 ◽  
Vol 117 (3) ◽  
pp. 1229-1238 ◽  
Author(s):  
Roxana A. Stefanescu ◽  
Susan E. Shore
Keyword(s):  
Spontaneous Activity ◽  
Cochlear Nucleus ◽  
Acetylcholine Receptors ◽  
Dorsal Cochlear Nucleus ◽  
Muscarinic Acetylcholine Receptors ◽  
Fusiform Cell ◽  
Baseline Activity ◽  
Stimulus Timing

Cholinergic modulation contributes to adaptive sensory processing by controlling spontaneous and stimulus-evoked neural activity and long-term synaptic plasticity. In the dorsal cochlear nucleus (DCN), in vitro activation of muscarinic acetylcholine receptors (mAChRs) alters the spontaneous activity of DCN neurons and interacts with N-methyl-d-aspartate (NMDA) and endocannabinoid receptors to modulate the plasticity of parallel fiber synapses onto fusiform cells by converting Hebbian long-term potentiation to anti-Hebbian long-term depression. Because noise exposure and tinnitus are known to increase spontaneous activity in fusiform cells as well as alter stimulus timing-dependent plasticity (StTDP), it is important to understand the contribution of mAChRs to in vivo spontaneous activity and plasticity in fusiform cells. In the present study, we blocked mAChRs actions by infusing atropine, a mAChR antagonist, into the DCN fusiform cell layer in normal hearing guinea pigs. Atropine delivery leads to decreased spontaneous firing rates and increased synchronization of fusiform cell spiking activity. Consistent with StTDP alterations observed in tinnitus animals, atropine infusion induced a dominant pattern of inversion of StTDP mean population learning rule from a Hebbian to an anti-Hebbian profile. Units preserving their initial Hebbian learning rules shifted toward more excitatory changes in StTDP, whereas units with initial suppressive learning rules transitioned toward a Hebbian profile. Together, these results implicate muscarinic cholinergic modulation as a factor in controlling in vivo fusiform cell baseline activity and plasticity, suggesting a central role in the maladaptive plasticity associated with tinnitus pathology. NEW & NOTEWORTHY This study is the first to use a novel method of atropine infusion directly into the fusiform cell layer of the dorsal cochlear nucleus coupled with simultaneous recordings of neural activity to clarify the contribution of muscarinic acetylcholine receptors (mAChRs) to in vivo fusiform cell baseline activity and auditory-somatosensory plasticity. We have determined that blocking the mAChRs increases the synchronization of spiking activity across the fusiform cell population and induces a dominant pattern of inversion in their stimulus timing-dependent plasticity. These modifications are consistent with similar changes established in previous tinnitus studies, suggesting that mAChRs might have a critical contribution in mediating the maladaptive alterations associated with tinnitus pathology. Blocking mAChRs also resulted in decreased fusiform cell spontaneous firing rates, which is in contrast with their tinnitus hyperactivity, suggesting that changes in the interactions between the cholinergic and GABAergic systems might also be an underlying factor in tinnitus pathology.

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