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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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Nav1.7 expression in vasopressin- and oxytocin-producing magnocellular neurosecretory cells in supraoptic nucleus. Magnocellular neurosecretory neurons (MSN) of the supraoptic nucleus (SON) exhibit robust vasopressin and oxytocin immunolabeling (green). MSN of the SON display Nav1.7 immunoreactivity (red). Double-immunocytochemical studies with antibodies to vasopressin or oxytocin and Nav1.7 demonstrate that both peptide-producing cell-types exhibit co-localization (magenta) with Nav1.7. Merged image of vasopressin or oxytocin with Nav1.7 is presented as magenta to enhance visualization of co-localization.
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Figure 1: Nav1.7 expression in vasopressin- and oxytocin-producing magnocellular neurosecretory cells in supraoptic nucleus. Magnocellular neurosecretory neurons (MSN) of the supraoptic nucleus (SON) exhibit robust vasopressin and oxytocin immunolabeling (green). MSN of the SON display Nav1.7 immunoreactivity (red). Double-immunocytochemical studies with antibodies to vasopressin or oxytocin and Nav1.7 demonstrate that both peptide-producing cell-types exhibit co-localization (magenta) with Nav1.7. Merged image of vasopressin or oxytocin with Nav1.7 is presented as magenta to enhance visualization of co-localization.

Mentions: Magnocellular neurosecretory cells in the supraoptic nucleus of control rats exhibited distinct NaV1.7 immunolabeling (Figure 1). Some magnocellular neurosecretory cells displayed moderate levels of NaV1.7 immunosignal, while other magnocellular neurosecretory cells exhibited a low level or no NaV1.7 immunofluorescence. Two types of magnocellular neurosecretory cells exist within the supraoptic nucleus, oxytocin-producing and vasopressin-producing, with little co-expression of these hormones in individual magnocellular neurosecretory cells. Both oxytocin- and vasopressin-producing magnocellular neurosecretory cells displayed NaV1.7 immunolabeling (Figure 1). Approximately 72% (33 of 46) of oxytocin-producing and 53% (59 of 112) of vasopressin-producing MSC expressed NaV1.7 labeling above background levels.


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 expression in vasopressin- and oxytocin-producing magnocellular neurosecretory cells in supraoptic nucleus. Magnocellular neurosecretory neurons (MSN) of the supraoptic nucleus (SON) exhibit robust vasopressin and oxytocin immunolabeling (green). MSN of the SON display Nav1.7 immunoreactivity (red). Double-immunocytochemical studies with antibodies to vasopressin or oxytocin and Nav1.7 demonstrate that both peptide-producing cell-types exhibit co-localization (magenta) with Nav1.7. Merged image of vasopressin or oxytocin with Nav1.7 is presented as magenta to enhance visualization of co-localization.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Nav1.7 expression in vasopressin- and oxytocin-producing magnocellular neurosecretory cells in supraoptic nucleus. Magnocellular neurosecretory neurons (MSN) of the supraoptic nucleus (SON) exhibit robust vasopressin and oxytocin immunolabeling (green). MSN of the SON display Nav1.7 immunoreactivity (red). Double-immunocytochemical studies with antibodies to vasopressin or oxytocin and Nav1.7 demonstrate that both peptide-producing cell-types exhibit co-localization (magenta) with Nav1.7. Merged image of vasopressin or oxytocin with Nav1.7 is presented as magenta to enhance visualization of co-localization.
Mentions: Magnocellular neurosecretory cells in the supraoptic nucleus of control rats exhibited distinct NaV1.7 immunolabeling (Figure 1). Some magnocellular neurosecretory cells displayed moderate levels of NaV1.7 immunosignal, while other magnocellular neurosecretory cells exhibited a low level or no NaV1.7 immunofluorescence. Two types of magnocellular neurosecretory cells exist within the supraoptic nucleus, oxytocin-producing and vasopressin-producing, with little co-expression of these hormones in individual magnocellular neurosecretory cells. Both oxytocin- and vasopressin-producing magnocellular neurosecretory cells displayed NaV1.7 immunolabeling (Figure 1). Approximately 72% (33 of 46) of oxytocin-producing and 53% (59 of 112) of vasopressin-producing MSC expressed NaV1.7 labeling above background levels.

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