Differential expression of respiratory long-term facilitation among inbred rat strains

Abstract

We tested the hypotheses that: (1) long-term facilitation (LTF) following acute intermittent hypoxia (AIH) varies among three inbred rat strains: Fischer 344 (F344), Brown Norway (BN) and Lewis rats and (2) ventral cervical spinal levels of genes important for phrenic LTF (pLTF) vary in association with pLTF magnitude. Lewis and F344, but not BN rats exhibited significant increases in phrenic and hypoglossal burst amplitude 60min post-AIH that were significantly greater than control experiments without AIH, indicating strain differences in phrenic (98%, 56% and 20%, respectively) and hypoglossal LTF (66%, 77% and 5%, respectively). Ventral spinal 5-HT(2A) receptor mRNA and protein levels were higher in F344 and Lewis versus BN, suggesting that higher 5-HT(2A) receptor levels are associated with greater pLTF. More complex relationships were found for 5-HT(7), BDNF and TrkB mRNA. BN had higher 5-HT(7) and TrkB mRNA versus F344; BN and Lewis had higher BDNF mRNA levels versus F344. Genetic variations in serotonergic function may underlie strain differences in AIH-induced pLTF.

Figure 1

Strain-dependent differences in long-term facilitation (LTF) at 60 min post-AIH in Brown Norway (BN), Fischer (F344) and Lewis rats. A) Lewis rats exhibited the largest phrenic LTF (pLTF) of the three strains, which was significantly greater than pLTF observed in F344, BN, or time control rats. F344 rats exhibited moderate pLTF, which was significantly greater than BN or time control rats not exposed to AIH. BN rats did not exhibit pLTF. B) F344 and Lewis rats exhibited similar XII LTF that was significantly different than BN or time control rats not exposed to AIH. ^a,b,c bars with different letters are significantly different from one another; p<0.05.

Figure 2

Strain-dependent differences in the change in burst frequency 60 min post-treatment in time controls and AIH-treated rats: Brown Norway (BN), Fischer (F344) and Lewis rats. F344 rats expressed a significantly greater increase in burst frequency from pre-AIH values than BN, Lewis or time control rats 60-min post-AIH. ^a,b, bars with different letters are significantly different from one another; p<0.05.

Figure 3

5-HT_2A protein levels in spinal regions encompassing the phrenic motor nucleus in Brown Norway (BN), Fischer (F344) and Lewis rats. A) Lewis rats had significantly higher 5-HT_2A protein levels in ventral C₃-C₅ than BN rats. B) Regression analysis indicates a significant relationship between 5-HT_2A receptor density near phrenic motoneurons and pLTF magnitude in BN, F344 and Lewis rats. * significantly different than BN rats; P<0.05.