Norepinephrine Facilitates the Development of the Murine Sweat Response But Is Not Essential

Tafari, A. Tsahai; Thomas, Steven; Palmiter, Richard D.

doi:10.1523/jneurosci.17-11-04275.1997

Cited by 27 publications

(2 citation statements)

References 22 publications

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“…A slightly modified standard method of sweat assay was performed ( 104 ). Mice were anesthetized (Zolpidem/xylazine 80–10 mg/kg) and pilocarpine (catalog #P6503, Sigma) was injected subcutaneously into the plantar surface of the foot (50 μg in 5 μl 0.9% saline).…”

Section: Methodsmentioning

confidence: 99%

Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV

Pacifico

Testa

Amodeo

et al. 2022

Human Molecular Genetics

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A functional nerve growth factor (NGF)–TrkA system is an essential requisite for the generation and maintenance of long-lasting thermal and mechanical hyperalgesia in adult mammals. Indeed, mutations in the gene encoding for TrkA are responsible for a rare condition, named Hereditary Sensory and Autonomic Neuropathy type IV (HSAN IV), characterized by the loss of response to noxious stimuli, anhidrosis and cognitive impairment. However, to date, there is no available mouse model to properly understand how the NGF–TrkA system can lead to pathological phenotypes that are distinctive of HSAN IV. Here, we report the generation of a knock-in mouse line carrying the HSAN IV TrkAR649W mutation. First, by in vitro biochemical and biophysical analyses, we show that the pathological R649W mutation leads to kinase-inactive TrkA also affecting its membrane dynamics and trafficking. In agreement with the HSAN IV human phenotype, TrkAR649W/m mice display a lower response to thermal and chemical noxious stimuli, correlating with reduced skin innervation, in addition to decreased sweating in comparison to TrkAh/m controls. Moreover, the R649W mutation decreases anxiety-like behavior and compromises cognitive abilities, by impairing spatial-working and social memory. Our results further uncover unexplored roles of TrkA in thermoregulation and sociability. In addition to accurately recapitulating the clinical manifestations of HSAN IV patients, our findings contribute to clarify the involvement of the NGF–TrkA system in pain sensation.

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Section: Methodsmentioning

confidence: 99%

Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV

Pacifico

Testa

Amodeo

et al. 2022

Human Molecular Genetics

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“…Sweating is controlled by the central nervous system and ANS via the neurotransmitters acetylcholine (ACh) and norepinephrine. Unlike ACh, norepinephrine plays only an indirect role in sweating [ 16 ]. Autonomic neuropathy results in hypohidrosis or reduced sweating [ 17 ].…”

Section: Peripheral Abnormalities In Patients With Type 2 Diabetesmentioning

confidence: 99%

Electrodermal activity and heart rate variability for detection of peripheral abnormalities in type 2 diabetes: A review

2023

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Modern medicine exhibits an upward trend towards non-invasive methods for early detection of disease and long-term monitoring of patients’ health. Diabetes mellitus and its complications are a promising area for implementation of new medical diagnostic devices. One of the most serious complications of diabetes is diabetic foot ulcer. The main causes responsible for diabetic foot ulcer are ischemia caused by peripheral artery disease and diabetic neuropathy caused by polyol pathway-induced oxidative stress. Autonomic neuropathy impairs function of sweat glands, which can be measured by electrodermal activity. On the other hand, autonomic neuropathy leads to changes in heart rate variability, which is used to assess autonomic regulation of the sinoatrial node. Both methods are enough sensitive to detect pathological changes caused by autonomic neuropathy and are promising screening methods for early diagnosis of diabetic neuropathy, which could prevent the onset of diabetic ulcer.

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Postnatal development of the cerebellum and the CNS adrenergic system is independent of norepinephrine and epinephrine

Jin

Kim

Harris

et al. 2004

J of Comparative Neurology

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A fundamental question in the formation of the nervous system is the extent to which a neurotransmitter contributes to the development of the neurons that synthesize and release it. A complementary question is whether neurotransmitter signaling contributes to the development of postsynaptic targets. Prior studies have suggested that adrenergic signaling may promote adrenergic neuronal proliferation or survival and may be critical for the postnatal development of the cerebellum. To test these possibilities genetically, we studied mice that are unable to synthesize norepinephrine and epinephrine (NE/E), the endogenous adrenergic receptor ligands, due to a disruption the gene for dopamine beta-hydroxylase. These mice develop postnatally in the absence of NE/E. Here we report that the adrenergic neurons of these mutant mice are present in normal numbers and locations and exhibit typical innervation patterns throughout the central nervous system (CNS), as assessed by immunostaining for tyrosine hydroxylase and the NE transporter. Furthermore, cerebellar cortical development (size, foliation, layering, cell number, and position), which proceeds to a large degree postnatally, is unaltered in the mutants. These results indicate that the fate and innervation pattern of the adrenergic neurons, as well as the development of the cerebellum, do not depend on postnatal signaling by NE/E. The results also suggest that when restoration of adrenergic signaling is performed in this mutant mouse model (by administering a synthetic precursor of NE), reversal of phenotypes is due to the synthesis and release of NE/E from adrenergic terminals that are distributed normally within the CNS.

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Norepinephrine Facilitates the Development of the Murine Sweat Response But Is Not Essential

Cited by 27 publications

References 22 publications

Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV

Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV

Electrodermal activity and heart rate variability for detection of peripheral abnormalities in type 2 diabetes: A review

Postnatal development of the cerebellum and the CNS adrenergic system is independent of norepinephrine and epinephrine

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