Effects of exposure to nerve growth factor antibodies on the developing nervous system of the rat: An experimental autoimmune approach

Abstract

An autoimmune method of NGF deprivation was used to characterize the effects of exposure to anti-NGF prenatally in utero and postnatally in milk. Offspring of NGF-immunized female rats were cross-fostered at birth with offspring of control female rats to separate the effects of in utero vs in milk exposure to maternal anti-NGF. In order to determine whether the effects of early exposure to maternal anti-NGF were permanent, rats were evaluated at maturity. Exposure to anti-NGF in utero or in milk resulted in significant decreases in protein and in both pre- and postsynaptic markers in the superior cervical ganglia (choline acetyltransferase and tyrosine hydroxylase, respectively). Significant decreases in norepinephrine levels were measured in peripheral tissues receiving sympathetic innervation (heart, uterus, and brown fat). In rats exposed to anti-NGF in utero , but not in milk, there was an approximately 30% decrease in total protein content in the dorsal root ganglia which was present at birth and in adulthood. The persistence of a decrease in protein content in mature sensory neurons reported here correlated with the previously reported loss of ability of sensory neurons exposed to anti-NGF in utero to retrogradely transport 125 I-NGF. Short adrenergic neurons, central adrenergic neurons, and adrenal medullary cells did not appear to be affected by either prenatal or postnatal exposure to maternal anti-NGF. The potential of the autoimmune approach in the study of the physiological role of NGF and other growth factors is discussed.