Naturally occurring motoneuron cell death in rat upper respiratory tract motor nuclei: A histological, fast dil and immunocytochemical study in the nucleus ambiguus

Abstract

The mammalian upper respiratory tract (URT) serves as the common modality for aspects of respiration, deglutition, and vocalization. Although these actions are dependent on coordinated and specific neuromuscular control, little is known about the development of URT control centers. As such, this study investigated the occurrence of naturally occurring motoneuron cell death (MCD) in the nucleus ambiguus (NA) of a developmental series of rats. Standard histological techniques were used to count motoneurons in the ventrolateral brainstem where the mature NA is found. In addition, the neural tracer, fast DiI, was used to determine whether motoneurons were still migrating into the region of the NA during the period that cell counts were first taken. Furthermore, to elucidate the potential effect of inadvertently counting large interneurons on the assessment of motoneuron numbers, an antibody to gamma-aminobutyric acid (GABA) was used. The results of this study have, for the first time, demonstrated that MCD occurs in a URT-related motor nucleus. Approximately a 50% cell death was observed during the prenatal development of NA, with no further loss seen postnatally. The fast DiI studies showed that by embryonic day 17, NA was fully formed, suggesting that motoneuron migration from the basal plate was complete. In addition, use of the GABA antibody showed a lack of inhibitory interneurons within the NA. The finding of MCD in the NA helps define a critical period in the formation of URT neuromuscular control. As the course of MCD is modifiable by epigenetic signals, insult to the organism during this prenatal period may compromise future URT control.

Naturally occurring motoneuron cell death in rat upper respiratory tract motor nuclei: A histological, fast Dil and immunocytochemical study in the hypoglossal nucleus

“…motor nuclei. For example, although several studies have indicated a postnatal period of motoneuron death (Tadaet al, 1979;Rootman et al, 1981;Scarisbrick et al, 1990), others have demonstrated an entirely prenatal course (Lance-Jones, 1982;Oppenheim, 1986;Oppenheim et al, 1986;Friedland et al, 1995). Our findings support the observations of the latter group, suggesting an entirely prenatal time course for the occurrence of MCD in the rodent.…”

“…Consistent with the findings just given, cell death in XI1 was also lower than the 50% cell death observed in the other URT motor nucleus, NA (Friedland et al, 1995). This difference in the amount of cell death may reflect the relative complexity of the motor nuclei.…”

“…Particular attention has been paid to the formation of the nucleus and the subsequent maturation of its motoneurons, specifically the occurrence of motoneuron cell death. In addition, we will here compare our findings on XI1 with our previously reported observations on the development of the NA, the other major URT motor nucleus (Friedland et al, 1995).…”

“…The initial appearance of XI1 was found to be at El4 while the first observation of NA was at El5 (Friedland et al, 1995). These observations may be the result of earlier generation of hypoglossal motoneurons.…”

“…E l 6 to E20 appears to represent a period of significant change in U R T motor nuclei (Friedland et al, 1995). Assuch.…”