Nerve Growth Factor-Tyrosine Kinase A Pathway Is Involved in Thermoregulation and Adaptation to Stress: Studies on Patients with Hereditary Sensory and Autonomic Neuropathy Type IV

Loewenthal, Neta; Levy, Jacov; Schreiber, Ruth; Pinsk, Vered; Perry, Zvi H.; Shorer, Zamir; Hershkovitz, Eli

doi:10.1203/01.pdr.0000155941.37155.41

Cited by 17 publications

(18 citation statements)

References 37 publications

(31 reference statements)

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“…2, 3, 8 10 Chromaffin cells are older phylogenetically and the findings in CIPA patients confirm animal data indicating that TRKA-NGF signaling is necessary for neuronal adrenergic but not required for chromaffin cell development. 20, 21 …”

Section: Discussionsupporting

confidence: 70%

Norepinephrine deficiency with normal blood pressure control in congenital insensitivity to pain with anhidrosis

Norcliffe‐Kaufmann¹,

Katz²,

Axelrod

et al. 2015

Annals of Neurology

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Objective Congenital insensitivity to pain with anhidrosis (CIPA) is caused by mutations in the NKTR1 gene. This affects the development of nerve growth factor (NGF)-dependent neurons including sympathetic cholinergic neurons in the skin causing anhidrosis. Cardiovascular and blood pressure regulation appears normal, but the integrity of sympathetic adrenergic neurons has not been tested. Methods We examined the effect of posture on blood pressure, heart rate, plasma concentration of catecholamines, vasopressin, endothelin and renin activity in 14 patients with CIPA, 10 patients with chronically deficient sympathetic activity (pure autonomic failure) and 15 normal age-matched controls. Results In all 14 patients with CIPA plasma norepinephrine levels were very low or undetectable and failed to increase when upright, yet upright blood pressure was well maintained. Plasma epinephrine levels were normal and increased upright. Plasma renin activity also increased appropriately when upright and after furosemide-induced volume depletion. Nitric oxide-mediated endothelial function was intact. Patients with pure autonomic failure also had very low levels of plasma norepinephrine both supine and upright, but in contrast to patients with CIPA failed to maintain blood pressure upright. Interpretation The results indicate that post-ganglionic sympathetic neurons are severely depleted in CIPA, but chromaffin cells of the adrenal medulla are spared. This confirms the differential effect of NGF signaling for sympathetic neural and chromaffin cell development. The finding that patients with CIPA maintain blood pressure well on standing challenges current concepts of the role of norepinephrine in the regulation of arterial pressure.

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Section: Discussionsupporting

confidence: 70%

Norepinephrine deficiency with normal blood pressure control in congenital insensitivity to pain with anhidrosis

Norcliffe‐Kaufmann¹,

Katz²,

Axelrod

et al. 2015

Annals of Neurology

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“…[46] Inadequate response to stress might contribute to significant mortality, morbidity. [7] In our case, the patient developed fulminant septicemia due to extensive skin ulceration and died of DIC with uncontrolled bleeding.…”

Section: Discussionmentioning

confidence: 76%

A case of hereditary sensory autonomic neuropathy type IV

Prashanth

Kamate

2012

Ann Indian Acad Neurol

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Hereditary sensory autonomic neuropathy type IV (HSAN -IV), also known as congenital insensitivity to pain with anhidrosis, is a very rare condition that presents in infancy with anhidrosis, absence of pain sensation and self -mutilation. Developmental delay and mental retardation are usually present. Ultrastructural study of the peripheral nerves demonstrates loss of the unmyelinated and small myelinated fibers. We here report a 8 year -old boy with HSAN IV with typical clinical features where the diagnosis was supported by nerve biopsy findings. However, our case was unusual since mental development was normal.

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“…By activating trkA, NGF causes a decrease in the after hyperpolarizations and increases the amplitude of vagus nerve-mediated nicotinic excitation. Direct evidence for a fundamental role for neurotrophins in regulating autonomic function in humans comes from the identification of mutations in trkA as a cause of hereditary, sensory, and autonomic neuropathy type IV (Loewenthal et al 2005). Those patients exhibit impaired thermoregulation, and deficits in sympathetic activation of the adrenal medulla.…”

Section: Neurotrophic Factors and The Regulation Of Ans Functionmentioning

confidence: 99%

Neurotrophic Factors in Autonomic Nervous System Plasticity and Dysfunction

Mattson

Wan

2008

Neuromol Med

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During development, neurotrophic factors are known to play important roles in regulating the survival of neurons in the autonomic nervous system (ANS) and the formation of their synaptic connectivity with their peripheral targets in the cardiovascular, digestive, and other organ systems. Emerging findings suggest that neurotrophic factors may also affect the functionality of the ANS during adult life and may, in part, mediate the effects of environmental factors such as exercise and dietary energy intake on ANS neurons and target cells. In this article, we describe the evidence that ANS neurons express receptors for multiple neurotrophic factors, and data suggesting that activation of those receptors can modify plasticity in the ANS. Neurotrophic factors that may regulate ANS function include brain-derived neurotrophic factor, nerve growth factor, insulin-like growth factors, and ciliary neurotrophic factor. The possibility that perturbed neurotrophic factor signaling is involved in the pathogenesis of ANS dysfunction in some neurological disorders is considered, together with implications for neurotrophic factor-based therapeutic interventions.

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Nerve Growth Factor-Tyrosine Kinase A Pathway Is Involved in Thermoregulation and Adaptation to Stress: Studies on Patients with Hereditary Sensory and Autonomic Neuropathy Type IV

Cited by 17 publications

References 37 publications

Norepinephrine deficiency with normal blood pressure control in congenital insensitivity to pain with anhidrosis

Norepinephrine deficiency with normal blood pressure control in congenital insensitivity to pain with anhidrosis

A case of hereditary sensory autonomic neuropathy type IV

Neurotrophic Factors in Autonomic Nervous System Plasticity and Dysfunction

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