Age and gender effects on serotonergic innervation and modulation of the hypoglossal motor nucleus

Aging results in structural, functional and neurochemical alterations in the respiratory system. Serotonin (5HT) plays a major role in breathing and the control of upper airway function. We tested the hypothesis that with increasing age there is a selective decrease in serotonergic modulation of respiratory motoneurons, in particular hypoglossal motoneurons to the tongue in male rats. We used light microscopic immunocytochemistry to study the distribution of 5HT axons and boutons throughout the hypoglossal nucleus in young and old rats male and female rats. Aged male rats (>12 months) had fewer serotonin immunoreactive axons and boutons in the hypoglossal nucleus than young male rats (<6 months). In contrast, 5HT immunoreactivity in the hypoglossal nucleus in female rats was higher than in age-matched males, and increased with age. In order to assess the functional consequences of this anatomical reorganization, we measured long term facilitation (LTF), a serotonin-dependent, long lasting increase in respiratory motor output following episodic hypoxia. LTF in the hypoglossal motor output was significantly reduced in aged male rats by comparison with young male rats [1]. In contrast, hypoglossal LTF increased in aged female rats in diestrus, but not in estrus. Taken together, these data suggest that in males, but not females, normal aging may result in decreased serotonergic facilitation of hypoglossal motoneurons that could result in reduced airway patency.