Abstract
Background: Extended exposure to allergen exacerbates asthma symptoms, in part via complex interactions between inflammatory cells and mediators. One consequence of these interactions is the triggering of local and central nervous system (CNS) neuronal activity that might further exacerbate the asthmalike symptoms by causing bronchoconstriction, mucous secretion, increased microvascular leak, and cough. One CNS region that might be particularly important is the caudomedial nucleus tractus solitarius (NTS). NTS neurons not only integrate primary afferent inputs from lung sensory nerve fibers but also have direct exposure to inhaled allergens and allergen-induced blood-borne inflammatory mediators via a deficient blood-brain barrier. Given the capacity of CNS neurons to undergo plasticity, allergen-induced changes in NTS neuronal properties could contribute to the exaggerated respiratory responses to extended allergen exposure. Objective: In a recently developed rhesus monkey model of allergic asthma, we tested the hypothesis that extended exposure to allergen increases the intrinsic excitability of NTS neurons. Methods: Three adult monkeys were sensitized and then repeatedly exposed to aerosols of house dust mite allergen; 4 monkeys served as controls. Whole-cell current-clamp recordings were made to measure 3 indices of excitability: resting membrane potential, input resistance, and number of action potentials evoked by current injections. Results: Extended allergen exposure depolarized the resting membrane potential by 14% and increased the number of action potentials evoked by current injections (5-fold). Conclusion: The finding that NTS neurons in a primate model of allergic asthma undergo intrinsic increases in excitability suggests that CNS mechanisms might contribute to the exaggerated symptoms in asthmatic individuals exposed to allergen.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 557-562 |
| Number of pages | 6 |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 108 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2001 |
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Keywords
- Asthma
- Solitary nucleus
- Vagus nerve
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Extended allergen exposure in asthmatic monkeys induces neuroplasticity in nucleus tractus solitarius. / Chen, Chao-Yin; Bonham, Ann C.; Schelegle, Edward S.; Gershwin, Laurel J; Schelegle, Edward S; Plopper, Charles.
In: Journal of Allergy and Clinical Immunology, Vol. 108, No. 4, 2001, p. 557-562.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Extended allergen exposure in asthmatic monkeys induces neuroplasticity in nucleus tractus solitarius
AU - Chen, Chao-Yin
AU - Bonham, Ann C.
AU - Schelegle, Edward S.
AU - Gershwin, Laurel J
AU - Schelegle, Edward S
AU - Plopper, Charles
PY - 2001
Y1 - 2001
N2 - Background: Extended exposure to allergen exacerbates asthma symptoms, in part via complex interactions between inflammatory cells and mediators. One consequence of these interactions is the triggering of local and central nervous system (CNS) neuronal activity that might further exacerbate the asthmalike symptoms by causing bronchoconstriction, mucous secretion, increased microvascular leak, and cough. One CNS region that might be particularly important is the caudomedial nucleus tractus solitarius (NTS). NTS neurons not only integrate primary afferent inputs from lung sensory nerve fibers but also have direct exposure to inhaled allergens and allergen-induced blood-borne inflammatory mediators via a deficient blood-brain barrier. Given the capacity of CNS neurons to undergo plasticity, allergen-induced changes in NTS neuronal properties could contribute to the exaggerated respiratory responses to extended allergen exposure. Objective: In a recently developed rhesus monkey model of allergic asthma, we tested the hypothesis that extended exposure to allergen increases the intrinsic excitability of NTS neurons. Methods: Three adult monkeys were sensitized and then repeatedly exposed to aerosols of house dust mite allergen; 4 monkeys served as controls. Whole-cell current-clamp recordings were made to measure 3 indices of excitability: resting membrane potential, input resistance, and number of action potentials evoked by current injections. Results: Extended allergen exposure depolarized the resting membrane potential by 14% and increased the number of action potentials evoked by current injections (5-fold). Conclusion: The finding that NTS neurons in a primate model of allergic asthma undergo intrinsic increases in excitability suggests that CNS mechanisms might contribute to the exaggerated symptoms in asthmatic individuals exposed to allergen.
AB - Background: Extended exposure to allergen exacerbates asthma symptoms, in part via complex interactions between inflammatory cells and mediators. One consequence of these interactions is the triggering of local and central nervous system (CNS) neuronal activity that might further exacerbate the asthmalike symptoms by causing bronchoconstriction, mucous secretion, increased microvascular leak, and cough. One CNS region that might be particularly important is the caudomedial nucleus tractus solitarius (NTS). NTS neurons not only integrate primary afferent inputs from lung sensory nerve fibers but also have direct exposure to inhaled allergens and allergen-induced blood-borne inflammatory mediators via a deficient blood-brain barrier. Given the capacity of CNS neurons to undergo plasticity, allergen-induced changes in NTS neuronal properties could contribute to the exaggerated respiratory responses to extended allergen exposure. Objective: In a recently developed rhesus monkey model of allergic asthma, we tested the hypothesis that extended exposure to allergen increases the intrinsic excitability of NTS neurons. Methods: Three adult monkeys were sensitized and then repeatedly exposed to aerosols of house dust mite allergen; 4 monkeys served as controls. Whole-cell current-clamp recordings were made to measure 3 indices of excitability: resting membrane potential, input resistance, and number of action potentials evoked by current injections. Results: Extended allergen exposure depolarized the resting membrane potential by 14% and increased the number of action potentials evoked by current injections (5-fold). Conclusion: The finding that NTS neurons in a primate model of allergic asthma undergo intrinsic increases in excitability suggests that CNS mechanisms might contribute to the exaggerated symptoms in asthmatic individuals exposed to allergen.
KW - Asthma
KW - Solitary nucleus
KW - Vagus nerve
UR - http://www.scopus.com/inward/record.url?scp=0034780395&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034780395&partnerID=8YFLogxK
U2 - 10.1067/mai.2001.118132
DO - 10.1067/mai.2001.118132
M3 - Article
C2 - 11590381
AN - SCOPUS:0034780395
VL - 108
SP - 557
EP - 562
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 4
ER -