Loss of motoneurons in the ventral compartment of the rat hypoglossal nucleus following early postnatal exposure to alcohol.
Perinatal alcohol exposure (AE) has multiple detrimental effects on cognitive and various behavioral outcomes, but little is known about its impact on the autonomic functions. In a rat model of fetal alcohol spectrum disorders (FASD), we investigated neurochemical and neuroanatomical alterations in two brainstem nuclei, the hypoglossal nucleus (XIIn) and the dorsal nucleus of the vagus nerve (Xdn). One group of male Sprague-Dawley rats (n=6) received 2.625 g/kg ethanol intragastrically twice daily on postnatal days (PD) 4-9, a period equivalent to the third trimester of human pregnancy, and another group (n=6) was sham-intubated. On PD 18-19, the rats were perfused and medullary sections were immunohistochemically processed for choline acetyltransferase (ChAT) or two aminergic receptors that mediate excitatory drive to motoneurons, α₁-adrenergic (α₁-R) and serotonin 2A (5-HT(2A)-R), and c-Fos. Based on ChAT labeling, AE rats had reduced numbers of motoneurons in the ventral XIIn (XIIn-v; 35.4±1.3 motoneurons per side and section vs. 40.0±1.2, p=0.022), but not in the dorsal XIIn or Xdn. Consistent with ChAT data, both the numbers of α₁-R-labeled motoneurons in the XIIn-v and the area of the XIIn-v measured using 5-HT(2A)-R staining were significantly smaller in AE rats (19.7±1.5 vs. 25.0±1.4, p=0.031 and 0.063 mm² ±0.002 vs. 0.074±0.002, p=0.002, respectively). Concurrently, both 5-HT(2A)-R and c-Fos staining tended to be higher in AE rats, suggesting an increased activation. Thus, postnatal AE causes motoneuronal loss in the XIIn-v. This may compromise upper airway control and contribute to increased risk of upper airway obstructions and sudden infant death in FASD victims.
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: georg.stettner@med.uni-goettingen.de.
Georg M
GM
Stettner
Leszek
L
Kubin
Denys V
DV
Volgin
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007002:Hypoglossal Nerve / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology*; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol
5-HT(2A)-R; AE; ChAT; DMSO; FASD; Fetal alcohol spectrum disorders (FASD); GD; PD; SIDS; Serotonin receptors; Sudden infant death syndrome (SIDS); Upper airway control; XIIn; XIIn-d; XIIn-e; XIIn-v; Xdn; alcohol exposure; alpha-1 adrenergic receptor; choline acetyltransferase; dimethyl sulfoxide; dorsal compartment of the hypoglossal nucleus; dorsal nucleus of the vagus nerve; entire hypoglossal nucleus; fetal alcohol spectrum disorders; gestational day; hypoglossal nucleus; postnatal day; serotonin 2A receptor; sudden infant death syndrome; ventral compartment of the hypoglossal nucleus; α(1)-R; α-Adrenergic receptors