Extended allergen exposure in asthmatic monkeys induces neuroplasticity in nucleus tractus solitarius.
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 asthma-like 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).


CONCLUSIONS
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.
Chen
C Y
CY
Department of Internal Medicine, School of Medicine, University of California at Davis, Sacramento, 95817, USA.
Bonham
A C
AC
Schelegle
E S
ES
Gershwin
L J
LJ
Plopper
C G
CG
Joad
J P
JP
D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D001249:Asthma / Q000209:etiology*; D004553:Electric Conductivity; D004781:Environmental Exposure; D005260:Female; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D008925:Mites / Q000276:immunology; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017552:Solitary Nucleus / Q000502:physiology*
D000485:Allergens