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Nick J Spencer - One of the best experts on this subject based on the ideXlab platform.
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identifying spinal afferent sensory Nerve Endings that innervate the marrow cavity and periosteum using anterograde tracing
The Journal of Comparative Neurology, 2020Co-Authors: Jenny Thai, Melinda Kyloh, Lee Travis, Nick J Spencer, Jason J IvanusicAbstract:While sensory and sympathetic neurons are known to innervate bone, previous studies have found it difficult to unequivocally identify and characterize only those that are of sensory origin. In this study, we have utilized an in vivo anterograde tracing technique to selectively label spinal afferent (sensory) Nerve Endings that innervate the periosteum and marrow cavity of murine long bones. Unilateral injections of dextran-biotin (anterograde tracer; 20% in saline, 50-100 nl) were made into L3-L5 dorsal root ganglia. After a 10-day recovery period to allow sufficient time for selective anterograde transport of the tracer to Nerve terminal Endings in bone, the periosteum (whole-mount) and underlying bone were collected, processed to reveal anterograde labeling, and immuno-labeled with antibodies directed against protein gene product (pan-neuronal marker; PGP9.5), tyrosine hydroxylase (sympathetic neuron marker; TH), calcitonin gene-related protein (peptidergic nociceptor marker; CGRP), and/or neurofilament 200 (myelinated axon marker; NF200). Anterograde-labeled Nerve Endings were dispersed throughout the periosteum and marrow cavity and could be identified in close apposition to blood vessels and at sites distant from them. The periosteum and the marrow cavity were each innervated by myelinated (NF200+) sensory neurons, and unmyelinated (NF200-) sensory neurons that were either peptidergic (CGRP+) or nonpeptidergic (CGRP-). Spinal afferent Nerve Endings did not express TH, and lacked the cylindrical morphology around blood vessels characteristic of sympathetic innervation. This approach to selective labeling of sensory Nerve terminal Endings will help to better identify how different sub-populations of sensory neurons, and their peripheral Nerve terminal Endings, interact with bone.
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identifying unique subtypes of spinal afferent Nerve Endings within the urinary bladder of mice
The Journal of Comparative Neurology, 2018Co-Authors: Nick J Spencer, Melinda Kyloh, Timothy J Hibberd, Sarah Greenheigh, Harman Sharma, Luke Grundy, Stuart M Brierley, Andrea M HarringtonAbstract:Spinal afferent neurons are responsible for the transduction and transmission of noxious (painful) stimuli and innocuous stimuli that do not reach conscious sensations from visceral organs to the central nervous system. Although the location of the Nerve cell bodies of spinal afferents is well known to reside in dorsal root ganglia (DRG), the morphology and location of peripheral Nerve Endings of spinal afferents that transduce sensory stimuli into action potentials is poorly understood. The individual Nerve Endings of spinal afferents that innervate the urinary bladder have never been unequivocally identified in any species. We used an anterograde tracing technique developed in our laboratory to selectively label only spinal afferents. Mice were anesthetized and unilateral injections of dextran-amine made into lumbosacral DRGs (L5-S2). Seven to nine days postsurgery, mice were euthanized, the urinary bladder removed, then fresh-fixed and stained for immunoreactivity to calcitonin-gene-related-peptide (CGRP). Four distinct morphological types of spinal afferent ending in the bladder were identified. Three types existed in the detrusor muscle and one major type in the sub-urothelium and urothelium. Most Nerve Endings were located in detrusor muscle where the three types could be identified as having: "branching", "simple", or "complex" morphology. The majority of spinal afferent Nerve Endings were CGRP-immunoreactive. Single spinal afferent axons bifurcated many times upon entering the bladder and developed varicosities along their axon terminal Endings. We present the first morphological identification of spinal afferent Nerve Endings in the mammalian urinary bladder.
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different types of spinal afferent Nerve Endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia
The Journal of Comparative Neurology, 2016Co-Authors: Nick J Spencer, Melinda Kyloh, Elizabeth A H Beckett, Simon J H Brookes, Timothy J HibberdAbstract:In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the Nerve Endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent Endings, but none on spinal afferent Endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent Nerve Endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed Nerve Endings in discrete anatomical layers. Most commonly, intraganglionic varicose Endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type Endings in the circular muscle and mucosa. Less commonly, Nerve Endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar Endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent Endings in the upper GI tract. Eight distinct types of spinal afferent Endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc.
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identification of different types of spinal afferent Nerve Endings that encode noxious and innocuous stimuli in the large intestine using a novel anterograde tracing technique
PLOS ONE, 2014Co-Authors: Nick J Spencer, Melinda Kyloh, Michael D DuffieldAbstract:In mammals, sensory stimuli in visceral organs, including those that underlie pain perception, are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRG). One of the major challenges in visceral organs has been how to identify the different types of Nerve Endings of spinal afferents that transduce sensory stimuli into action potentials. The reason why spinal afferent Nerve Endings have been so challenging to identify is because no techniques have been available, until now, that can selectively label only spinal afferents, in high resolution. We have utilized an anterograde tracing technique, recently developed in our laboratory, which facilitates selective labeling of only spinal afferent axons and their Nerve Endings in visceral organs. Mice were anesthetized, lumbosacral DRGs surgically exposed, then injected with dextran-amine. Seven days post-surgery, the large intestine was removed. The characteristics of thirteen types of spinal afferent Nerve Endings were identified in detail. The greatest proportion of Nerve Endings was in submucosa (32%), circular muscle (25%) and myenteric ganglia (22%). Two morphologically distinct classes innervated myenteric ganglia. These were most commonly a novel class of intraganglionic varicose Endings (IGVEs) and occasionally rectal intraganglionic laminar Endings (rIGLEs). Three distinct classes of varicose Nerve Endings were found to innervate the submucosa and circular muscle, while one class innervated internodal strands, blood vessels, crypts of lieberkuhn, the mucosa and the longitudinal muscle. Distinct populations of sensory Endings were CGRP-positive. We present the first complete characterization of the different types of spinal afferent Nerve Endings in a mammalian visceral organ. The findings reveal an unexpectedly complex array of different types of primary afferent Endings that innervate specific layers of the large intestine. Some of the novel classes of Nerve Endings identified must underlie the transduction of noxious and/or innocuous stimuli from the large intestine.
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a novel anterograde neuronal tracing technique to selectively label spinal afferent Nerve Endings that encode noxious and innocuous stimuli in visceral organs
Neurogastroenterology and Motility, 2014Co-Authors: Melinda Kyloh, Nick J SpencerAbstract:BACKGROUND: One major weakness in our understanding of pain perception from visceral organs is the lack of knowledge of the location, morphology and neurochemistry of all the different types of spinal afferent Nerve Endings, which detect noxious and innocuous stimuli. This is because we lack techniques to selectively label only spinal afferents. Our aim was to develop an anterograde tracing technique that labels only spinal afferent Nerve Endings in visceral organs, without also labeling all other classes of extrinsic afferent and efferent Nerves. METHODS: Mice were anesthetized with isoflurane and dextran-biotin injected, via glass micropipettes (diameter 5 μm), into L6 and S1 dorsal root ganglia. Mice recovered for 7 days, were then euthanized and the colon removed. KEY RESULTS: Anterograde labeling revealed multiple unique classes of afferent Endings that terminated within distinct anatomical layers of the colon and rectum. We characterized a particular class of intramuscular ending in the circular muscle (CM) layer of the colon that consists of multiple varicose axons that project circumferentially. CONCLUSIONS & INFERENCES: We demonstrate a technique for selective anterograde labeling of spinal afferent Nerve Endings in visceral organs. This approach facilitates selective visualization of the precise morphology and location of the different classes of spinal afferent Endings, without visual interference caused by indiscriminant labeling of other classes of afferent and efferent Nerve axons which also innervate internal organs. We have used this new technique to identify and describe the details of a particular class of intramuscular spinal afferent ending in the CM layer of mouse large intestine.
Melinda Kyloh - One of the best experts on this subject based on the ideXlab platform.
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identifying spinal afferent sensory Nerve Endings that innervate the marrow cavity and periosteum using anterograde tracing
The Journal of Comparative Neurology, 2020Co-Authors: Jenny Thai, Melinda Kyloh, Lee Travis, Nick J Spencer, Jason J IvanusicAbstract:While sensory and sympathetic neurons are known to innervate bone, previous studies have found it difficult to unequivocally identify and characterize only those that are of sensory origin. In this study, we have utilized an in vivo anterograde tracing technique to selectively label spinal afferent (sensory) Nerve Endings that innervate the periosteum and marrow cavity of murine long bones. Unilateral injections of dextran-biotin (anterograde tracer; 20% in saline, 50-100 nl) were made into L3-L5 dorsal root ganglia. After a 10-day recovery period to allow sufficient time for selective anterograde transport of the tracer to Nerve terminal Endings in bone, the periosteum (whole-mount) and underlying bone were collected, processed to reveal anterograde labeling, and immuno-labeled with antibodies directed against protein gene product (pan-neuronal marker; PGP9.5), tyrosine hydroxylase (sympathetic neuron marker; TH), calcitonin gene-related protein (peptidergic nociceptor marker; CGRP), and/or neurofilament 200 (myelinated axon marker; NF200). Anterograde-labeled Nerve Endings were dispersed throughout the periosteum and marrow cavity and could be identified in close apposition to blood vessels and at sites distant from them. The periosteum and the marrow cavity were each innervated by myelinated (NF200+) sensory neurons, and unmyelinated (NF200-) sensory neurons that were either peptidergic (CGRP+) or nonpeptidergic (CGRP-). Spinal afferent Nerve Endings did not express TH, and lacked the cylindrical morphology around blood vessels characteristic of sympathetic innervation. This approach to selective labeling of sensory Nerve terminal Endings will help to better identify how different sub-populations of sensory neurons, and their peripheral Nerve terminal Endings, interact with bone.
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identifying unique subtypes of spinal afferent Nerve Endings within the urinary bladder of mice
The Journal of Comparative Neurology, 2018Co-Authors: Nick J Spencer, Melinda Kyloh, Timothy J Hibberd, Sarah Greenheigh, Harman Sharma, Luke Grundy, Stuart M Brierley, Andrea M HarringtonAbstract:Spinal afferent neurons are responsible for the transduction and transmission of noxious (painful) stimuli and innocuous stimuli that do not reach conscious sensations from visceral organs to the central nervous system. Although the location of the Nerve cell bodies of spinal afferents is well known to reside in dorsal root ganglia (DRG), the morphology and location of peripheral Nerve Endings of spinal afferents that transduce sensory stimuli into action potentials is poorly understood. The individual Nerve Endings of spinal afferents that innervate the urinary bladder have never been unequivocally identified in any species. We used an anterograde tracing technique developed in our laboratory to selectively label only spinal afferents. Mice were anesthetized and unilateral injections of dextran-amine made into lumbosacral DRGs (L5-S2). Seven to nine days postsurgery, mice were euthanized, the urinary bladder removed, then fresh-fixed and stained for immunoreactivity to calcitonin-gene-related-peptide (CGRP). Four distinct morphological types of spinal afferent ending in the bladder were identified. Three types existed in the detrusor muscle and one major type in the sub-urothelium and urothelium. Most Nerve Endings were located in detrusor muscle where the three types could be identified as having: "branching", "simple", or "complex" morphology. The majority of spinal afferent Nerve Endings were CGRP-immunoreactive. Single spinal afferent axons bifurcated many times upon entering the bladder and developed varicosities along their axon terminal Endings. We present the first morphological identification of spinal afferent Nerve Endings in the mammalian urinary bladder.
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different types of spinal afferent Nerve Endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia
The Journal of Comparative Neurology, 2016Co-Authors: Nick J Spencer, Melinda Kyloh, Elizabeth A H Beckett, Simon J H Brookes, Timothy J HibberdAbstract:In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the Nerve Endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent Endings, but none on spinal afferent Endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent Nerve Endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed Nerve Endings in discrete anatomical layers. Most commonly, intraganglionic varicose Endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type Endings in the circular muscle and mucosa. Less commonly, Nerve Endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar Endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent Endings in the upper GI tract. Eight distinct types of spinal afferent Endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc.
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identification of different types of spinal afferent Nerve Endings that encode noxious and innocuous stimuli in the large intestine using a novel anterograde tracing technique
PLOS ONE, 2014Co-Authors: Nick J Spencer, Melinda Kyloh, Michael D DuffieldAbstract:In mammals, sensory stimuli in visceral organs, including those that underlie pain perception, are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRG). One of the major challenges in visceral organs has been how to identify the different types of Nerve Endings of spinal afferents that transduce sensory stimuli into action potentials. The reason why spinal afferent Nerve Endings have been so challenging to identify is because no techniques have been available, until now, that can selectively label only spinal afferents, in high resolution. We have utilized an anterograde tracing technique, recently developed in our laboratory, which facilitates selective labeling of only spinal afferent axons and their Nerve Endings in visceral organs. Mice were anesthetized, lumbosacral DRGs surgically exposed, then injected with dextran-amine. Seven days post-surgery, the large intestine was removed. The characteristics of thirteen types of spinal afferent Nerve Endings were identified in detail. The greatest proportion of Nerve Endings was in submucosa (32%), circular muscle (25%) and myenteric ganglia (22%). Two morphologically distinct classes innervated myenteric ganglia. These were most commonly a novel class of intraganglionic varicose Endings (IGVEs) and occasionally rectal intraganglionic laminar Endings (rIGLEs). Three distinct classes of varicose Nerve Endings were found to innervate the submucosa and circular muscle, while one class innervated internodal strands, blood vessels, crypts of lieberkuhn, the mucosa and the longitudinal muscle. Distinct populations of sensory Endings were CGRP-positive. We present the first complete characterization of the different types of spinal afferent Nerve Endings in a mammalian visceral organ. The findings reveal an unexpectedly complex array of different types of primary afferent Endings that innervate specific layers of the large intestine. Some of the novel classes of Nerve Endings identified must underlie the transduction of noxious and/or innocuous stimuli from the large intestine.
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a novel anterograde neuronal tracing technique to selectively label spinal afferent Nerve Endings that encode noxious and innocuous stimuli in visceral organs
Neurogastroenterology and Motility, 2014Co-Authors: Melinda Kyloh, Nick J SpencerAbstract:BACKGROUND: One major weakness in our understanding of pain perception from visceral organs is the lack of knowledge of the location, morphology and neurochemistry of all the different types of spinal afferent Nerve Endings, which detect noxious and innocuous stimuli. This is because we lack techniques to selectively label only spinal afferents. Our aim was to develop an anterograde tracing technique that labels only spinal afferent Nerve Endings in visceral organs, without also labeling all other classes of extrinsic afferent and efferent Nerves. METHODS: Mice were anesthetized with isoflurane and dextran-biotin injected, via glass micropipettes (diameter 5 μm), into L6 and S1 dorsal root ganglia. Mice recovered for 7 days, were then euthanized and the colon removed. KEY RESULTS: Anterograde labeling revealed multiple unique classes of afferent Endings that terminated within distinct anatomical layers of the colon and rectum. We characterized a particular class of intramuscular ending in the circular muscle (CM) layer of the colon that consists of multiple varicose axons that project circumferentially. CONCLUSIONS & INFERENCES: We demonstrate a technique for selective anterograde labeling of spinal afferent Nerve Endings in visceral organs. This approach facilitates selective visualization of the precise morphology and location of the different classes of spinal afferent Endings, without visual interference caused by indiscriminant labeling of other classes of afferent and efferent Nerve axons which also innervate internal organs. We have used this new technique to identify and describe the details of a particular class of intramuscular spinal afferent ending in the CM layer of mouse large intestine.
Donald M Kuhn - One of the best experts on this subject based on the ideXlab platform.
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3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine Nerve Endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter.
Journal of neurochemistry, 2015Co-Authors: John H. Anneken, Mariana Angoa-pérez, Donald M KuhnAbstract:Methylone, 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone are psychoactive ingredients of 'bath salts' and their abuse represents a growing public health care concern. These drugs are cathinone derivatives and are classified chemically as β-ketoamphetamines. Because of their close structural similarity to the amphetamines, methylone, MDPV, and mephedrone share most of their pharmacological, neurochemical, and behavioral properties. One point of divergence in their actions is the ability to cause damage to the CNS. Unlike methamphetamine, the β-ketoamphetamines do not damage dopamine (DA) Nerve Endings. However, mephedrone has been shown to significantly accentuate methamphetamine neurotoxicity. Bath salt formulations contain numerous different psychoactive ingredients, and individuals who abuse bath salts also coabuse other illicit drugs. Therefore, we have evaluated the effects of methylone, MDPV, mephedrone, and methamphetamine on DA Nerve Endings. The β-ketoamphetamines alone or in all possible two-drug combinations do not result in damage to DA Nerve Endings but do cause hyperthermia. MDPV completely protects against the neurotoxic effects of methamphetamine while methylone accentuates it. Neither MDPV nor methylone attenuates the hyperthermic effects of methamphetamine. The potent neuroprotective effects of MDPV extend to amphetamine-, 3,4-methylenedioxymethamphetamine-, and MPTP-induced neurotoxicity. These results indicate that β-ketoamphetamine drugs that are non-substrate blockers of the DA transporter (i.e., MDPV) protect against methamphetamine neurotoxicity, whereas those that are substrates for uptake by the DA transporter and which cause DA release (i.e., methylone, mephedrone) accentuate neurotoxicity. METH (a) enters DA Nerve Endings via the DAT, causes leakage of DA into the cytoplasm and then into the synapse via DAT-mediated reverse transport. Methylone (METHY) and mephedrone (MEPH; b), like METH, are substrates for the DAT but release DA from cytoplasmic pools selectively. When METH is combined with METHY or MEPH (c), DA efflux and neurotoxicity are enhanced. MDPV (d), which is a non-substrate blocker of the DAT, prevents METH uptake and efflux of DA. Therefore, bath salts that are substrates for the DAT and release DA (METHY, MEPH) accentuate METH neurotoxicity, whereas those that are non-substrate blockers of the DAT (MDPV) are neuroprotective.
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Effects of combined treatment with mephedrone and methamphetamine or 3,4-methylenedioxymethamphetamine on serotonin Nerve Endings of the hippocampus.
Life sciences, 2013Co-Authors: Mariana Angoa-pérez, Michael J Kane, Dina M Francescutti, Nieves Herrera-mundo, Donald M KuhnAbstract:Abstract Aims Mephedrone is a stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Although mephedrone does not damage dopamine Nerve Endings it increases the neurotoxicity of amphetamine, methamphetamine and MDMA. The effects of mephedrone on serotonin (5HT) Nerve Endings are not fully understood, with some investigators reporting damage while others conclude it does not. Presently, we investigate if mephedrone given alone or with methamphetamine or MDMA damages 5HT Nerve Endings of the hippocampus. Main methods The status of 5HT Nerve Endings in the hippocampus of female C57BL mice was assessed through measures of 5HT by HPLC and by immunoblot analysis of serotonin transporter (SERT) and tryptophan hydroxylase 2 (TPH2), selective markers of 5HT Nerve Endings. Astrocytosis was assessed through measures of glial fibrillary acidic protein (GFAP) (immunoblotting) and microglial activation was determined by histochemical staining with Isolectin B4. Key findings Mephedrone alone did not cause persistent reductions in the levels of 5HT, SERT or TPH2. Methamphetamine and MDMA alone caused mild reductions in 5HT but did not change SERT and TPH2 levels. Combined treatment with mephedrone and methamphetamine or MDMA did not change the status of 5HT Nerve Endings to an extent that was different from either drug alone. Significance Mephedrone does not cause toxicity to 5HT Nerve Endings of the hippocampus. When co-administered with methamphetamine or MDMA, drugs that are often co-abused with mephedrone by humans, toxicity is not increased as is the case for dopamine Nerve Endings when these drugs are taken together.
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mephedrone does not damage dopamine Nerve Endings of the striatum but enhances the neurotoxicity of methamphetamine amphetamine and mdma
Journal of Neurochemistry, 2013Co-Authors: Mariana Angoaperez, Michael J Kane, Dina M Francescutti, Mrudang Shah, David M Thomas, Denise I Briggs, Catherine E Sykes, Donald M KuhnAbstract:Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its re-uptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA Nerve Endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20, or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (four injections of 2.5 or 5.0 mg/kg at 2 h intervals). The integrity of DA Nerve Endings of the striatum was assessed through measures of DA, DAT, and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and 3,4-methylenedioxymethamphetamine on DA Nerve Endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. As mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA Nerve Endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity.
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mephedrone an abused psychoactive component of bath salts and methamphetamine congener does not cause neurotoxicity to dopamine Nerve Endings of the striatum
Journal of Neurochemistry, 2012Co-Authors: Mariana Angoaperez, Michael J Kane, Dina M Francescutti, Katherine E Sykes, Mrudang Shah, Abiy M Mohammed, David M Thomas, Donald M KuhnAbstract:Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine with close structural analogy to substituted amphetamines and cathinone derivatives. Abuse of mephedrone has increased dramatically in recent years and has become a significant public health problem in the US and Europe. Unfortunately, very little information is available on the pharmacological and neurochemical actions of mephedrone. In light of the proven abuse potential of mephedrone and considering its similarity to methamphetamine and methcathinone, it is particularly important to know if mephedrone shares with these agents an ability to cause damage to dopamine Nerve Endings of the striatum. Accordingly, we treated mice with a binge-like regimen of mephedrone (4X 20 or 40 mg/kg) and examined the striatum for evidence of neurotoxicity 2 or 7 days after treatment. While mephedrone caused hyperthermia and locomotor stimulation, it did not lower striatal levels of dopamine, tyrosine hydroxylase or the dopamine transporter under any of the treatment conditions used presently. Furthermore, mephedrone did not cause microglial activation in striatum nor did it increase glial fibrillary acidic protein levels. Taken together, these surprising results suggest that mephedrone, despite its numerous mechanistic overlaps with methamphetamine and the cathinone derivatives, does not cause neurotoxicity to dopamine Nerve Endings of the striatum.
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the role of endogenous serotonin in methamphetamine induced neurotoxicity to dopamine Nerve Endings of the striatum
Journal of Neurochemistry, 2010Co-Authors: Mrudang Shah, David M Thomas, Donald M Kuhn, Mariana Angoa Perez, Dina M FrancescuttiverbeemAbstract:Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the striatum where long-term DA depletion and microglial activation are maximal. Endogenous DA has been implicated as a critical participant in METH-induced neurotoxicity, most likely as a substrate for non-enzymatic oxidation by METH-generated reactive oxygen species. The striatum is also extensively innervated by serotonin (5HT) Nerve Endings and this neurochemical system is modified by METH in much the same manner as seen in DA Nerve Endings (i.e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores). 5HT can also be modified by reactive oxygen species to form highly reactive species that damage neurons but its role in METH neurotoxicity has not been assessed. Increases in 5HT levels with 5-hydroxytryptophan do not change METH-induced neurotoxicity to the DA Nerve Endings as revealed by reductions in DA, tyrosine hydroxylase and dopamine transporter levels. Partial reductions in 5HT with p-chlorophenylalanine are without effect on METH toxicity, despite the fact that p-chlorophenylalanine largely prevents METH-induced hyperthermia. Mice lacking the gene for brain tryptophan hydroxylase 2 are devoid of brain 5HT and respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia. Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA Nerve Endings of the striatum.
Hirohiko Azuma - One of the best experts on this subject based on the ideXlab platform.
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Morphology and distribution of Nerve Endings in the human triangular fibrocartilage complex
Journal of Hand Surgery, 1998Co-Authors: M. Ohmori, Hirohiko AzumaAbstract:We studied the morphology and distribution of Nerve Endings in the human triangular fibrocartilage complex using both silver staining and immunohistochemical staining using a protein specific to Nerve fibres. Free Nerve Endings were found in the ulnar side of the triangular fibrocartilage complex, especially in the ulnar collateral ligament, meniscus homologue and the adjacent collagen fibre area of the peripheral part of the ulnar side of the articular disc. Meissner's and Krause's corpuscles were observed in the ulnar collateral ligament and meniscus homologue. The fact that free Nerve Endings were observed in the meniscus homologue and adjacent collagen fibre area of the peripheral part of the ulnar side of the articular disc suggests that this disc may be a source of wrist pain. The presence of Nerve end bulbs in the triangular fibrocartilage complex also suggests a possible role for corpuscles as mechanoreceptors.
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The Nerve Endings of the acetabular labrum.
Clinical Orthopaedics and Related Research, 1995Co-Authors: Hirohiko AzumaAbstract:: The Nerve Endings of the human acetabular labrum were investigated. Twenty-three acetabular labra were obtained from 24 fresh human cadavers, stained with Suzuki's silver impregnation and an immunohistochemical technique for neurogenic specific protein S-100, and examined by light and electron microscopy. Ramified free Nerve Endings were seen in all specimens by silver staining, and also were observed by the immunohistochemical technique for S-100 protein. Sensory Nerve end organs, such as a Vater-Pacini corpuscle, Golgi-Mazzoni corpuscle, Ruffini corpuscle, and articular corpuscle (Krause corpuscle), were observed by silver staining. Collagen fibers were scattered sparsely in the superficial layer of the labrum, and Nerve Endings were observed mostly in this region. Collagen fibers were sparse, and Nerve Endings also were observed in some regions among the collagen fiber bundles in the inner layer. Innervation of the acetabular labrum was confirmed in this study, suggesting that Nerve Endings in the labrum may be involved in nociceptive and proprioceptive mechanisms.
Elisabet Hagert - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical mapping of sensory Nerve Endings in the human triangular fibrocartilage complex
Clinical Orthopaedics and Related Research, 2015Co-Authors: Susanne Rein, H Zwipp, Manuel Semisch, Marc Garciaelias, Alex Lluch, Elisabet HagertAbstract:Background The triangular fibrocartilage complex is the main stabilizer of the distal radioulnar joint. While static joint stability is constituted by osseous and ligamentous integrity, the dynamic aspects of joint stability chiefly concern proprioceptive control of the compressive and directional muscular forces acting on the joint. Therefore, an investigation of the pattern and types of sensory Nerve Endings gives more insight in dynamic distal radioulnar joint stability.
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Comparative analysis of inter- and intraligamentous distribution of sensory Nerve Endings in ankle ligaments: a cadaver study.
Foot & Ankle International, 2013Co-Authors: Susanne Rein, H Zwipp, Uwe Hanisch, Sophie Lwowski, Armin Fieguth, Elisabet HagertAbstract:Background: The aim of this study was to analyze the inter-, intraligamentous, and side-related patterns of sensory Nerve Endings in ankle ligaments. Methods: A total of 140 ligaments from 10 cadaver feet were harvested. Lateral: calcaneofibular, anterior-, posterior talofibular; sinus tarsi: lateral- (IERL), intermediate-, medial-roots inferior extensor retinaculum, talocalcaneal oblique and canalis tarsi (CTL); medial: tibionavicular (TNL), tibiocalcaneal (TCL), superficial tibiotalar, anterior/posterior tibiotalar portions; syndesmosis: anterior tibiofibular. Following immunohistochemical staining, the innervation and vascularity was analyzed between ligaments of each anatomical complex, left/right feet, and within the 5 levels of each ligament. Results: Significantly more free Nerve Endings were seen in all ligaments as compared to Ruffini, Pacini, Golgi-like, and unclassifiable corpuscles (P ≤ .005). The IERL had significantly more free Nerve Endings and blood vessels than the CTL (P ≤ .001). No significant differences were seen in the side-related distribution, except for Ruffini Endings in right TCL (P = .016) and unclassifiable corpuscles in left TNL (P = .008). The intraligamentous analysis in general revealed no significant differences in mechanoreceptor distribution. Conclusions: The IERL at the entrance of the sinus tarsi contained more free Nerve Endings and blood vessels, as compared to the deeper situated CTL. Despite different biomechanical functions in the medial and lateral ligaments, the interligamentous distribution of sensory Nerve Endings was equal. Clinical Relevance: The intrinsic innervation patterns of the ankle ligaments provides an understanding of their innate healing capacities following injury as well as the proprioception properties in postoperative rehabilitation.
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Immunohistochemical analysis of sensory Nerve Endings in ankle ligaments: a cadaver study.
Cells Tissues Organs, 2012Co-Authors: Susanne Rein, Elisabet Hagert, Uwe Hanisch, Sophie Lwowski, Armin Fieguth, H ZwippAbstract:Background: The aim of this study was to analyze the pattern and types of sensory Nerve Endings in ankle ligaments using immunohistochemical techniques, in order to gain more insight into functional ankle stability. Methods: One hundred forty ligaments from 10 cadaver feet were included: the calcaneofibular and anterior/posterior talofibular ligaments from the lateral complex; inferior extensor retinaculum complex, talocalcaneal oblique and canalis tarsi ligaments from the sinus tarsi; deltoid ligament with its individual portions from the medial complex, and anterior tibiofibular ligament (ATiFL) from the syndesmosis. Mechanoreceptors were classified according to Freeman and Wyke [Acta Anat (Basel) 1967;68:321–333] after staining with hematoxylin-eosin, low-affinity neurotrophin receptor p75, protein gene product 9.5, and S-100 protein. Results: Free Nerve Endings were the predominant sensory Endings in all four complexes, with the greatest density in the lateral and medial complexes; followed by Ruffini Endings, unclassifiable corpuscles, Pacini corpuscles, and Golgi-like Endings. Ruffini Endings were significantly more prevalent in the ATiFL than in the medial complex, and more common than Pacini corpuscles and Golgi-like Endings in the lateral, medial, and sinus tarsi complexes. A greater number of blood vessels correlated with a greater number of free Nerve Endings. There was a negative correlation between the number of Ruffini Endings, unclassifiable corpuscles, and age. Conclusions: Free Nerve Endings are the dominant mechanoreceptor type in the ankle ligaments, followed by Ruffini Endings. The ligaments of the lateral and medial ankle complexes are more innervated than the sinus tarsi ligaments.
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Immunofluorescent triple-staining technique to identify sensory Nerve Endings in human thumb ligaments.
Cells Tissues Organs, 2011Co-Authors: Amy L. Ladd, Elisabet HagertAbstract:Ligament innervation purportedly plays a critical role in stability, proprioception and pathology of joints with minimal bony constraints. The human thumb carpometacarpal (CMC) joint is such a joint: with a complex saddle configuration and wide circumduction, its constraint is primarily ligamentous and it is prone to osteoarthritis. CMC reconstruction is the most commonly performed arthritis surgery in the upper extremity. Little, however, is known about CMC ligament innervation. We describe a novel triple-staining immunofluorescence technique using the markers for low-affinity neurotrophin receptor p75, the pan-neuronal marker protein gene product (PGP) 9.5 and 4′,6′-diamidino-2-phenylindole (DAPI) to simultaneously detect and differentiate between specific sensory Nerve Endings: the Pacini corpuscles, the Ruffini Endings and Nerve fascicles. Five primary CMC ligaments (dorsal radial, dorsal central, posterior oblique, anterior oblique and ulnar collateral ligaments) were harvested from 10 fresh-frozen human cadaver hands. Following paraffin sectioning, each ligament was stained using a triple-stain technique and imaged with fluorescence microscopy. Multidimensional acquisition permitted simultaneous capture of images at different wavelengths. Pacini corpuscles were distinguished by their distinct p75 immunoreactive capsules, and Ruffini Endings by their overlapping p75 and PGP9.5 immunoreactive dendritic Nerve Endings. Simultaneous use of PGP9.5, p75 and DAPI immunofluorescence to analyze innervation patterns in human ligaments provides descriptive analysis of staining patterns and receptor structure as well as clues as to the proprioceptive function of CMC ligaments and the joint as a whole. Our novel findings of CMC ligament innervation augment the study of normal and pathological joint mechanics in this joint so prone to osteoarthritis.