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Exposure to Allergen Causes Changes in NTS Neural Activities after Intratracheal Capsaicin Application, in Endocannabinoid Levels and in the Glia Morphology of NTS.

Spaziano G, Luongo L, Guida F, Petrosino S, Matteis M, Palazzo E, Sullo N, de Novellis V, Di Marzo V, Rossi F, Maione S, D'Agostino B - Biomed Res Int (2015)

Bottom Line: Immunohistochemical studies, endocannabinoid, and palmitoylethanolamide quantification in the NTS were also performed.This study provides evidence that allergen sensitization in the NTS induced: (1) increase in the neural firing response to intratracheal capsaicin application, (2) increase of endocannabinoid anandamide and palmitoylethanolamide, a reduction of 2-arachidonoylglycerol levels in the NTS, (3) glial cell activation, and (4) prevention by a Group III metabotropic glutamate receptor activation of neural firing response to intratracheal application of capsaicin in both naïve and sensitized rats.Therefore, normalization of ovalbumin-induced NTS neural sensitization could open up the prospect of new treatments based on the recovery of specific brain nuclei function and for extensive studies on acute or long-term efficacy of selective mGlu ligand, in models of bronchial hyperreactivity.

View Article: PubMed Central - PubMed

Affiliation: Endocannabinoid Research Group, Section of Pharmacology, "L. Donatelli," Department of Experimental Medicine, School of Medicine, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.

ABSTRACT
Allergen exposure may induce changes in the brainstem secondary neurons, with neural sensitization of the nucleus solitary tract (NTS), which in turn can be considered one of the causes of the airway hyperresponsiveness, a characteristic feature of asthma. We evaluated neurofunctional, morphological, and biochemical changes in the NTS of naive or sensitized rats. To evaluate the cell firing activity of NTS, in vivo electrophysiological experiments were performed before and after capsaicin challenge in sensitized or naive rats. Immunohistochemical studies, endocannabinoid, and palmitoylethanolamide quantification in the NTS were also performed. This study provides evidence that allergen sensitization in the NTS induced: (1) increase in the neural firing response to intratracheal capsaicin application, (2) increase of endocannabinoid anandamide and palmitoylethanolamide, a reduction of 2-arachidonoylglycerol levels in the NTS, (3) glial cell activation, and (4) prevention by a Group III metabotropic glutamate receptor activation of neural firing response to intratracheal application of capsaicin in both naïve and sensitized rats. Therefore, normalization of ovalbumin-induced NTS neural sensitization could open up the prospect of new treatments based on the recovery of specific brain nuclei function and for extensive studies on acute or long-term efficacy of selective mGlu ligand, in models of bronchial hyperreactivity.

No MeSH data available.


Related in: MedlinePlus

Airway responsiveness to methacholine in ovalbumin (sensitized) or saline treated rats (control) (n = 5). **P < 0.01 compared with control group. Circles represent single values and squares represent mean values.
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fig1: Airway responsiveness to methacholine in ovalbumin (sensitized) or saline treated rats (control) (n = 5). **P < 0.01 compared with control group. Circles represent single values and squares represent mean values.

Mentions: In sensitized rats, OVA aerosol caused an acute bronchoconstriction, with an approximately threefold greater increase in RL and decrease in Cdyn respect to an aerosol of saline solution (data not shown). OVA challenge exposure resulted in an increase of airway responsiveness to inhaled histamine, approximately fourfold (P < 0.01) when compared with saline challenge (PC100: 69 mg/mL; 18 mg/mL saline and ova groups, resp.) (Figure 1). Moreover, sensitization caused an enhancement of the endogenous TRPV1/CB1 “hydrid” agonist, anandamide, and of the endogenous PPARα agonist palmitoylethanolamide levels in the NTS area, whilst lowering the levels of the CB1-selective endocannabinoid 2-AG (Table 1).


Exposure to Allergen Causes Changes in NTS Neural Activities after Intratracheal Capsaicin Application, in Endocannabinoid Levels and in the Glia Morphology of NTS.

Spaziano G, Luongo L, Guida F, Petrosino S, Matteis M, Palazzo E, Sullo N, de Novellis V, Di Marzo V, Rossi F, Maione S, D'Agostino B - Biomed Res Int (2015)

Airway responsiveness to methacholine in ovalbumin (sensitized) or saline treated rats (control) (n = 5). **P < 0.01 compared with control group. Circles represent single values and squares represent mean values.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383154&req=5

fig1: Airway responsiveness to methacholine in ovalbumin (sensitized) or saline treated rats (control) (n = 5). **P < 0.01 compared with control group. Circles represent single values and squares represent mean values.
Mentions: In sensitized rats, OVA aerosol caused an acute bronchoconstriction, with an approximately threefold greater increase in RL and decrease in Cdyn respect to an aerosol of saline solution (data not shown). OVA challenge exposure resulted in an increase of airway responsiveness to inhaled histamine, approximately fourfold (P < 0.01) when compared with saline challenge (PC100: 69 mg/mL; 18 mg/mL saline and ova groups, resp.) (Figure 1). Moreover, sensitization caused an enhancement of the endogenous TRPV1/CB1 “hydrid” agonist, anandamide, and of the endogenous PPARα agonist palmitoylethanolamide levels in the NTS area, whilst lowering the levels of the CB1-selective endocannabinoid 2-AG (Table 1).

Bottom Line: Immunohistochemical studies, endocannabinoid, and palmitoylethanolamide quantification in the NTS were also performed.This study provides evidence that allergen sensitization in the NTS induced: (1) increase in the neural firing response to intratracheal capsaicin application, (2) increase of endocannabinoid anandamide and palmitoylethanolamide, a reduction of 2-arachidonoylglycerol levels in the NTS, (3) glial cell activation, and (4) prevention by a Group III metabotropic glutamate receptor activation of neural firing response to intratracheal application of capsaicin in both naïve and sensitized rats.Therefore, normalization of ovalbumin-induced NTS neural sensitization could open up the prospect of new treatments based on the recovery of specific brain nuclei function and for extensive studies on acute or long-term efficacy of selective mGlu ligand, in models of bronchial hyperreactivity.

View Article: PubMed Central - PubMed

Affiliation: Endocannabinoid Research Group, Section of Pharmacology, "L. Donatelli," Department of Experimental Medicine, School of Medicine, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.

ABSTRACT
Allergen exposure may induce changes in the brainstem secondary neurons, with neural sensitization of the nucleus solitary tract (NTS), which in turn can be considered one of the causes of the airway hyperresponsiveness, a characteristic feature of asthma. We evaluated neurofunctional, morphological, and biochemical changes in the NTS of naive or sensitized rats. To evaluate the cell firing activity of NTS, in vivo electrophysiological experiments were performed before and after capsaicin challenge in sensitized or naive rats. Immunohistochemical studies, endocannabinoid, and palmitoylethanolamide quantification in the NTS were also performed. This study provides evidence that allergen sensitization in the NTS induced: (1) increase in the neural firing response to intratracheal capsaicin application, (2) increase of endocannabinoid anandamide and palmitoylethanolamide, a reduction of 2-arachidonoylglycerol levels in the NTS, (3) glial cell activation, and (4) prevention by a Group III metabotropic glutamate receptor activation of neural firing response to intratracheal application of capsaicin in both naïve and sensitized rats. Therefore, normalization of ovalbumin-induced NTS neural sensitization could open up the prospect of new treatments based on the recovery of specific brain nuclei function and for extensive studies on acute or long-term efficacy of selective mGlu ligand, in models of bronchial hyperreactivity.

No MeSH data available.


Related in: MedlinePlus