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NaV1.7: stress-induced changes in immunoreactivity within magnocellular neurosecretory neurons of the supraoptic nucleus.

Black JA, Hoeijmakers JG, Faber CG, Merkies IS, Waxman SG - Mol Pain (2013)

Bottom Line: NaV1.7 is preferentially expressed, at relatively high levels, in peripheral neurons, and is often referred to as a "peripheral" sodium channel, and NaV1.7-specific blockers are under study as potential pain therapeutics which might be expected to have minimal CNS side effects.NaV1.7 is present within neurosecretory neurons of rat supraoptic nucleus, where the level of immunoreactivity is dynamic, increasing in response to osmotic stress.Whether NaV1.7 levels are up-regulated within the human hypothalamus in response to environmental factors or stress, and whether NaV1.7 plays a functional role in human hypothalamus, is not yet known.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.

ABSTRACT

Background: NaV1.7 is preferentially expressed, at relatively high levels, in peripheral neurons, and is often referred to as a "peripheral" sodium channel, and NaV1.7-specific blockers are under study as potential pain therapeutics which might be expected to have minimal CNS side effects. However, occasional reports of patients with NaV1.7 gain-of-function mutations and apparent hypothalamic dysfunction have appeared. The two sodium channels previously studied within the rat hypothalamic supraoptic nucleus, NaV1.2 and NaV1.6, display up-regulated expression in response to osmotic stress.

Results: Here we show that NaV1.7 is present within vasopressin-producing neurons and oxytocin-producing neurons within the rat hypothalamus, and demonstrate that the level of Nav1.7 immunoreactivity is increased in these cells in response to osmotic stress.

Conclusions: NaV1.7 is present within neurosecretory neurons of rat supraoptic nucleus, where the level of immunoreactivity is dynamic, increasing in response to osmotic stress. Whether NaV1.7 levels are up-regulated within the human hypothalamus in response to environmental factors or stress, and whether NaV1.7 plays a functional role in human hypothalamus, is not yet known. Until these questions are resolved, the present findings suggest the need for careful assessment of hypothalamic function in patients with NaV1.7 mutations, especially when subjected to stress, and for monitoring of hypothalamic function as NaV1.7 blocking agents are studied.

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Related in: MedlinePlus

Nav1.7 is upregulated in magnocellular neurosecretory neurons of supraoptic nucleus following salt loading. (A) Magnocellular neurosecretory neurons (MSN) within supraoptic nucleus (SON) of control rats exhibit Nav1.7 immunolabeling. Following salt-loading, MSN display more prominent Nav1.7 immunoreactivity compared to control rats. (B) Quantification of Nav1.7 immunosignal within the SON demonstrates an approximately two-fold increase in Nav1.7 immunofluorescence in SON of salt-loaded rats compared to control rats.
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Figure 2: Nav1.7 is upregulated in magnocellular neurosecretory neurons of supraoptic nucleus following salt loading. (A) Magnocellular neurosecretory neurons (MSN) within supraoptic nucleus (SON) of control rats exhibit Nav1.7 immunolabeling. Following salt-loading, MSN display more prominent Nav1.7 immunoreactivity compared to control rats. (B) Quantification of Nav1.7 immunosignal within the SON demonstrates an approximately two-fold increase in Nav1.7 immunofluorescence in SON of salt-loaded rats compared to control rats.

Mentions: Salt-loading induced a substantial increase in the level of NaV1.7 immunoreactivity in magnocellular neurosecretory cells of the supraoptic nucleus compared to magnocellular neurosecretory cells in control rats (Figure 2A). In addition to the detection of greater numbers of magnocellular neurosecretory cells that displayed NaV1.7 immunolabeling, the intensity of NaV1.7 signal in some magnocellular neurosecretory neurons was markedly greater than that observed in magnocellular neurosecretory cells from control rats. Quantification of the mean intensity of NaV1.7 signal within the circumscribed supraoptic nucleus demonstrated a significant up regulation of NaV1.7 in response to salt-loading challenge (Figure 2B). These observations demonstrate that, in addition to up regulation of the TTX-S sodium channels NaV1.2 and NaV1.6 within magnocellular neurosecretory cells of the supraoptic nucleus with salt-loading, the level of NaV1.7 protein in these cells is significantly increased in osmotically-challenged rats.


NaV1.7: stress-induced changes in immunoreactivity within magnocellular neurosecretory neurons of the supraoptic nucleus.

Black JA, Hoeijmakers JG, Faber CG, Merkies IS, Waxman SG - Mol Pain (2013)

Nav1.7 is upregulated in magnocellular neurosecretory neurons of supraoptic nucleus following salt loading. (A) Magnocellular neurosecretory neurons (MSN) within supraoptic nucleus (SON) of control rats exhibit Nav1.7 immunolabeling. Following salt-loading, MSN display more prominent Nav1.7 immunoreactivity compared to control rats. (B) Quantification of Nav1.7 immunosignal within the SON demonstrates an approximately two-fold increase in Nav1.7 immunofluorescence in SON of salt-loaded rats compared to control rats.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750570&req=5

Figure 2: Nav1.7 is upregulated in magnocellular neurosecretory neurons of supraoptic nucleus following salt loading. (A) Magnocellular neurosecretory neurons (MSN) within supraoptic nucleus (SON) of control rats exhibit Nav1.7 immunolabeling. Following salt-loading, MSN display more prominent Nav1.7 immunoreactivity compared to control rats. (B) Quantification of Nav1.7 immunosignal within the SON demonstrates an approximately two-fold increase in Nav1.7 immunofluorescence in SON of salt-loaded rats compared to control rats.
Mentions: Salt-loading induced a substantial increase in the level of NaV1.7 immunoreactivity in magnocellular neurosecretory cells of the supraoptic nucleus compared to magnocellular neurosecretory cells in control rats (Figure 2A). In addition to the detection of greater numbers of magnocellular neurosecretory cells that displayed NaV1.7 immunolabeling, the intensity of NaV1.7 signal in some magnocellular neurosecretory neurons was markedly greater than that observed in magnocellular neurosecretory cells from control rats. Quantification of the mean intensity of NaV1.7 signal within the circumscribed supraoptic nucleus demonstrated a significant up regulation of NaV1.7 in response to salt-loading challenge (Figure 2B). These observations demonstrate that, in addition to up regulation of the TTX-S sodium channels NaV1.2 and NaV1.6 within magnocellular neurosecretory cells of the supraoptic nucleus with salt-loading, the level of NaV1.7 protein in these cells is significantly increased in osmotically-challenged rats.

Bottom Line: NaV1.7 is preferentially expressed, at relatively high levels, in peripheral neurons, and is often referred to as a "peripheral" sodium channel, and NaV1.7-specific blockers are under study as potential pain therapeutics which might be expected to have minimal CNS side effects.NaV1.7 is present within neurosecretory neurons of rat supraoptic nucleus, where the level of immunoreactivity is dynamic, increasing in response to osmotic stress.Whether NaV1.7 levels are up-regulated within the human hypothalamus in response to environmental factors or stress, and whether NaV1.7 plays a functional role in human hypothalamus, is not yet known.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.

ABSTRACT

Background: NaV1.7 is preferentially expressed, at relatively high levels, in peripheral neurons, and is often referred to as a "peripheral" sodium channel, and NaV1.7-specific blockers are under study as potential pain therapeutics which might be expected to have minimal CNS side effects. However, occasional reports of patients with NaV1.7 gain-of-function mutations and apparent hypothalamic dysfunction have appeared. The two sodium channels previously studied within the rat hypothalamic supraoptic nucleus, NaV1.2 and NaV1.6, display up-regulated expression in response to osmotic stress.

Results: Here we show that NaV1.7 is present within vasopressin-producing neurons and oxytocin-producing neurons within the rat hypothalamus, and demonstrate that the level of Nav1.7 immunoreactivity is increased in these cells in response to osmotic stress.

Conclusions: NaV1.7 is present within neurosecretory neurons of rat supraoptic nucleus, where the level of immunoreactivity is dynamic, increasing in response to osmotic stress. Whether NaV1.7 levels are up-regulated within the human hypothalamus in response to environmental factors or stress, and whether NaV1.7 plays a functional role in human hypothalamus, is not yet known. Until these questions are resolved, the present findings suggest the need for careful assessment of hypothalamic function in patients with NaV1.7 mutations, especially when subjected to stress, and for monitoring of hypothalamic function as NaV1.7 blocking agents are studied.

Show MeSH
Related in: MedlinePlus