Eph/ephrin interactions modulate vascular sympathetic innervation.

Ephs and ephrins are membrane-bound proteins that interact to modulate axon growth and neuronal function. We tested the hypothesis that eph/ephrin interactions affected the growth and function of vascular sympathetic innervation. Using RT-PCR analyses, we detected both classes of ephs (A and B) and both classes of ephrins (A and B) in sympathetic ganglia from neonatal and adult rats. Both classes of ephs (A and B) and both classes of ephrins (A and B) bound to the cell bodies and neurites of dissociated postganglionic sympathetic neurons. Messenger RNAs encoding for both classes of ephs (A and B) and both classes of ephrins (A and B) were also detected in sympathetically innervated arteries from neonatal and adult rats. These data suggest that ephrins/ephs on nerve fibers of postganglionic sympathetic neurons could interact with ephs/ephrins on cells in innervated arteries. We found that ephA4 reduced reinnervation of denervated femoral arteries. Reinnervation in the presence of ephA4-Fc (38.9±6.6%) was significantly less than that in the presence of IgG-Fc (62±10%; n=5; p<0.05; one-tailed unpaired t-test). These data indicate that eph/ephrin interactions modulated the growth of vascular sympathetic innervation. We also found that ephA4 increased basal release of norepinephrine from nerve terminals of isolated tail arteries. These data indicate that eph/ephrin interactions affect the growth and function of vascular sympathetic innervation.

Vascular-derived artemin: a determinant of vascular sympathetic innervation?

Vascular sympathetic innervation is an important determinant of blood pressure and blood flow. The mechanisms that determine vascular sympathetic innervation are not well understood. The present study tests the hypothesis that vascular-derived artemin promotes the development of sympathetic innervation to blood vessels by promoting sympathetic axon growth. RT-PCR and Western analyses indicate that artemin is expressed by cultured vascular smooth muscle and arteries, and artemin coreceptors, glial cell-derived neurotrophic factor family receptor alpha3 and ret, are expressed by postganglionic sympathetic neurons. The effects of artemin on axon growth were assessed on explants of neonatal rat sympathetic ganglia. In the presence, but not in the absence, of nerve growth factor, exogenous artemin stimulated neurite growth. Femoral arteries (FA) from adult rats contain artemin, and these arteries stimulated sympathetic neurite growth. Growth in the presence of FA was 92.2 +/- 11.9 mm, and that in the absence of FA was 26.3 +/- 5.4 mm (P < 0.05). FA stimulation of axon growth was reduced by an antibody that neutralized the activity of artemin (P < 0.05). These data indicate that artemin is expressed in arteries, and its receptors are expressed and functional in the postganglionic sympathetic neurons that innervate them. This suggests that artemin may be a determinant of vascular sympathetic innervation.

Dibromoacetic acid, a commonly occurring water disinfection by-product, does not affect follicular populations in neonatal rats.

To investigate whether the mechanism of dibromoacetic acid (DBA) toxicity involves disruption of primordial germ cell migration and/or follicular formation, pregnant and lactating female Sprague-Dawley rats were gavaged daily with 0, 1, 5, or 50 mg DBA/kg body weight beginning on gestation day 17 and continuing through postnatal day 7. Reproductive parameters in 4 groups (n = 10 per group) of female neonatal rats exposed to DBA were examined. Maternal weight, litter size, and gender ratio did not differ across treatment groups, and major organ weights (spleen, liver, kidneys, uterus, and ovary) did not differ from control. Ovaries were serially sectioned at 8 microm and every eighth section was used for morphometry. All healthy follicles within a section were categorized into one of five types and the area of section was measured. Follicular populations at all stages of development did not differ among treatment groups. Thus, exposure to DBA during the period of follicular formation did not affect follicular populations in neonatal rats. These data suggest that rodents may not be a useful model for DBA toxicity assessment. Further research into species differences in the mechanism and timing of DBA toxicity is warranted.