scholarly journals Imaging in vivo acetylcholine release in the peripheral nervous system with a fluorescent nanosensor

2021 ◽  
Vol 118 (14) ◽  
pp. e2023807118
Author(s):  
Junfei Xia ◽  
Hongrong Yang ◽  
Michelle Mu ◽  
Nicholas Micovic ◽  
Kira E. Poskanzer ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Neurological Diseases ◽  
Signal Propagation ◽  
Tissue Level ◽  
Quantitative Detection ◽  
Efferent Nerve ◽  
Submandibular Ganglia ◽  
Dose Dependent

The ability to monitor the release of neurotransmitters during synaptic transmission would significantly impact the diagnosis and treatment of neurological diseases. Here, we present a DNA-based enzymatic nanosensor for quantitative detection of acetylcholine (ACh) in the peripheral nervous system of living mice. ACh nanosensors consist of DNA as a scaffold, acetylcholinesterase as a recognition component, pH-sensitive fluorophores as signal generators, and α-bungarotoxin as a targeting moiety. We demonstrate the utility of the nanosensors in the submandibular ganglia of living mice to sensitively detect ACh ranging from 0.228 to 358 μM. In addition, the sensor response upon electrical stimulation of the efferent nerve is dose dependent, reversible, and we observe a reduction of ∼76% in sensor signal upon pharmacological inhibition of ACh release. Equipped with an advanced imaging processing tool, we further spatially resolve ACh signal propagation on the tissue level. Our platform enables sensitive measurement and mapping of ACh transmission in the peripheral nervous system.

scholarly journals A DNA-based optical nanosensor for in vivo imaging of acetylcholine in the peripheral nervous system

2020 ◽  
Author(s):  
Junfei Xia ◽  
Hongrong Yang ◽  
Michelle Mu ◽  
Nicholas Micovic ◽  
Kira E. Poskanzer ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Signal Propagation ◽  
Tissue Level ◽  
Quantitative Detection ◽  
Efferent Nerve ◽  
Imaging Processing ◽  
Submandibular Ganglia ◽  
Dose Dependent

AbstractThe ability to monitor the release of neurotransmitters during synaptic transmission would significantly impact the diagnosis and treatment of neurological disease. Here, we present a DNA-based enzymatic nanosensor for quantitative detection of acetylcholine (ACh) in the peripheral nervous system of living mice. ACh nanosensors consist of DNA as a scaffold, acetylcholinesterase as a recognition component, pH-sensitive fluorophores as signal generators, and α-bungarotoxin as a targeting moiety. We demonstrate the utility of the nanosensors in the submandibular ganglia of living mice to sensitively detect ACh ranging from 0.228 μM to 358 μM. In addition, the sensor response upon electrical stimulation of the efferent nerve is dose-dependent, reversible, and we observe a reduction of ~76% in sensor signal upon pharmacological inhibition of ACh release. Equipped with an advanced imaging processing tool, we further spatially resolve ACh signal propagation on the tissue level. Our platform enables sensitive measurement and mapping of ACh transmission in the peripheral nervous system.

Toward in vivo determination of peripheral nervous system immune activity in amyotrophic lateral sclerosis

2019 ◽  
Vol 59 (5) ◽  
pp. 567-576 ◽  
Author(s):  
Stefanie Schreiber ◽  
Frank Schreiber ◽  
Cornelia Garz ◽  
Grazyna Debska‐Vielhaber ◽  
Anne Assmann ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Activity ◽  
Lateral Sclerosis

scholarly journals In Vitro Analysis of Transneuronal Spread of an Alphaherpesvirus Infection in Peripheral Nervous System Neurons

2007 ◽  
Vol 81 (13) ◽  
pp. 6846-6857 ◽  
Author(s):  
B. Feierbach ◽  
M. Bisher ◽  
J. Goodhouse ◽  
L. W. Enquist
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Pseudorabies Virus ◽  
Viral Glycoprotein ◽  
In Vitro System ◽  
Vitro Analysis ◽  
In Vitro Analysis ◽  
Postsynaptic Target

ABSTRACT The neurotropic alphaherpesviruses invade and spread in the nervous system in a directional manner between synaptically connected neurons. Until now, this property has been studied only in living animals and has not been accessible to in vitro analysis. In this study, we describe an in vitro system in which cultured peripheral nervous system neurons are separated from their neuron targets by an isolator chamber ring. Using pseudorabies virus (PRV), an alphaherpesvirus capable of transneuronal spread in neural circuits of many animals, we have recapitulated in vitro all known genetic requirements for retrograde and anterograde transneuronal spread as determined previously in vivo. We show that in vitro transneuronal spread requires intact axons and the presence of the viral proteins gE, gI, and Us9. We also show that transneuronal spread is dependent on the viral glycoprotein gB, which is required for membrane fusion, but not on gD, which is required for extracellular spread. We demonstrate ultrastructural differences between anterograde- and retrograde-traveling virions. Finally, we show live imaging of dynamic fluorescent virion components in axons and postsynaptic target neurons.

scholarly journals Large scale in vivo recording of sensory neuron activity with GCaMP6

2017 ◽  
Author(s):  
Kim I Chisholm ◽  
Nikita Khovanov ◽  
Douglas M Lopes ◽  
Federica La Russa ◽  
Stephen B McMahon
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Action Potentials ◽  
Large Scale ◽  
Primary Afferents ◽  
Neuron Activity ◽  
Functional Responses ◽  
Single Action

AbstractGreater emphasis on the study of intact cellular networks in their physiological environment has led to rapid advances in intravital imaging in the central nervous system, while the peripheral system remains largely unexplored. To assess large networks of sensory neurons we selectively label primary afferents with GCaMP6s and visualise their functional responses in vivo to peripheral stimulation. We show that we are able to monitor simultaneously the activity of hundreds of sensory neurons with sensitivity sufficient to detect, in most cases, single action potentials with a typical rise time of around 200 milliseconds, and an exponential decay with a time constant of approximately 700 milliseconds. Using this sensitive technique we are able to show that large scale recordings demonstrate the recently disputed polymodality of nociceptive primary afferents with between 40-80% of thermally sensitive DRG neurons responding also to noxious mechanical stimulation. We also specifically assess the small population of peripheral cold fibres and demonstrate significant sensitisation to cooling after a model of sterile and persistent inflammation, with significantly increased sensitivity already at decreases of 5°C when compared to uninflamed responses. This not only reveals interesting new insights into the (patho)physiology of the peripheral nervous system but also demonstrates the sensitivity of this imaging technique to physiological changes in primary afferents.Significance StatementMost of our functional understanding of the peripheral nervous system has come from single unit recordings. However, the acquisition of such data is labour-intensive and usually ‘low yield’. Moreover, some questions are best addressed by studying populations of neurons. To this end we report on a system that monitors activity in hundreds of single sensory neurons simultaneously, with sufficient sensitivity to detect in most cases single action potentials. We use this technique to characterise nociceptor properties and demonstrate polymodality in the majority of neurons and their sensitization under inflammatory conditions. We therefore believe this approach will be very useful for the studies of the somatosensory system in general and pain in particular.

scholarly journals COVID-19 Infection and Neurological Complications: Present Findings and Future Predictions

2020 ◽  
Vol 54 (5) ◽  
pp. 364-369 ◽  
Author(s):  
Ettore Beghi ◽  
Valery Feigin ◽  
Valeria Caso ◽  
Paola Santalucia ◽  
Giancarlo Logroscino
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Viral Infections ◽  
Neurological Diseases ◽  
Neurological Complications ◽  
Influenza Viruses ◽  
Surveillance Systems ◽  
Care Needs ◽  
The Past ◽  
Immune Mediated

The present outbreak caused by SARS-CoV-2, an influenza virus with neurotropic potential, presents with neurological manifestations in a large proportion of the affected individuals. Disorders of the central and peripheral nervous system are all present, while stroke, ataxia, seizures, and depressed level of consciousness are more common in severely affected patients. People with these severe complications are most likely elderly with medical comorbidities, especially hypertension and other vascular risk factors. However, postinfectious complications are also expected. Neurological disorders as sequelae of influenza viruses have been repeatedly documented in the past and include symptoms, signs, and diseases occurring during the acute phase and, not rarely, during follow-up. Postinfectious neurological complications are the result of the activation of immune mechanisms and can explain the insurgence of immune-mediated diseases, including the Guillain-Barré syndrome and other diseases of the central and peripheral nervous system that in the past occurred as complications of viral infections and occasionally with vaccines. For these reasons, the present outbreak calls for the introduction of surveillance systems to monitor changes in the frequency of several immune-mediated neurological diseases. These changes will determine a reorganization of the measures apt to describe the interaction between the virus, the environment, and the host in areas of different dimensions, from local communities to regions with several millions of inhabitants. The public health system, mainly primary care, needs to be strengthened to ensure that research and development efforts are directed toward right needs and directions. To cope with the present pandemic, better collaboration is required between international organizations along with more research funding, and tools in order to detect, treat, and prevent future epidemics.

scholarly journals GAP-43 is expressed by nonmyelin-forming Schwann cells of the peripheral nervous system.

1992 ◽  
Vol 116 (6) ◽  
pp. 1455-1464 ◽  
Author(s):  
R Curtis ◽  
H J Stewart ◽  
S M Hall ◽  
G P Wilkin ◽  
R Mirsky ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Glial Cells ◽  
Distal Stump ◽  
Metabolic Labeling ◽  
General Role

Recently it has been demonstrated that the growth-associated protein GAP-43 is not confined to neurons but is also expressed by certain central nervous system glial cells in tissue culture and in vivo. This study has extended these observations to the major class of glial cells in the peripheral nervous system, Schwann cells. Using immunohistochemical techniques, we show that GAP-43 immunoreactivity is present in Schwann cell precursors and in mature non-myelin-forming Schwann cells both in vitro and in vivo. This immunoreactivity is shown by Western blotting to be a membrane-associated protein that comigrates with purified central nervous system GAP-43. Furthermore, metabolic labeling experiments demonstrate definitively that Schwann cells in culture can synthesize GAP-43. Mature myelin-forming Schwann cells do not express GAP-43 but when Schwann cells are removed from axonal contact in vivo by nerve transection GAP-43 expression is upregulated in nearly all Schwann cells of the distal stump by 4 wk after denervation. In contrast, in cultured Schwann cells GAP-43 is not rapidly upregulated in cells that have been making myelin in vivo. Thus the regulation of GAP-43 appears to be complex and different from that of other proteins associated with nonmyelin-forming Schwann cells such as N-CAM, glial fibrillary acidic protein, A5E3, and nerve growth factor receptor, which are rapidly upregulated in myelin-forming cells after loss of axonal contact. These observations suggest that GAP-43 may play a more general role in the nervous system than previously supposed.

In vivo imaging of inflammation in the peripheral nervous system by 19F MRI

2011 ◽  
Vol 229 (2) ◽  
pp. 494-501 ◽  
Author(s):  
G. Weise ◽  
T.C. Basse-Luesebrink ◽  
C. Wessig ◽  
P.M. Jakob ◽  
G. Stoll
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
In Vivo Imaging ◽  
19F Mri

scholarly journals The Angiotensin II Type 2 Receptor, a Target for Protection and Regeneration of the Peripheral Nervous System?

2021 ◽  
Vol 14 (3) ◽  
pp. 175
Author(s):  
Aurore Danigo ◽  
Amandine Rovini ◽  
Flavien Bessaguet ◽  
Hichem Bouchenaki ◽  
Amandine Bernard ◽  
...  
Keyword(s):  
Nervous System ◽  
Angiotensin Ii ◽  
Peripheral Nervous System ◽  
Neuroprotective Effects ◽  
Pharmacological Studies ◽  
The Central Nervous System ◽  
G Protein Coupled

Preclinical evidence, accumulated over the past decade, indicates that the angiotensin II type 2 receptor (AT2R) stimulation exerts significant neuroprotective effects in various animal models of neuronal injury, notably in the central nervous system. While the atypical G protein-coupled receptor superfamily nature of AT2R and its related signaling are still under investigation, pharmacological studies have shown that stimulation of AT2R leads to neuritogenesis in vitro and in vivo. In this review, we focus on the potential neuroprotective and neuroregenerative roles of AT2R specifically in the peripheral nervous system (PNS). The first section describes the evidence for AT2R expression in the PNS and highlights current controversies concerning the cellular distribution of the receptor. The second section focuses on AT2R signaling implicated in neuronal survival and in neurite outgrowth. The following sections review the relatively few preclinical studies highlighting the putative neuroprotective and neuroregenerative effects of AT2R stimulation in the context of peripheral neuropathy.

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