Glial cell line-derived neurotrophic factor (GDNF), a new neurotrophic factor for motoneurones

Glial cell line-derived neurotrophic factor (GDNF), a new neurotrophic factor for motoneurones. the development of vibrissae and incisor 4′-Ethynyl-2′-deoxyadenosine and molar teeth, as well as the innervation of 4′-Ethynyl-2′-deoxyadenosine these structures, and found no variations between null-mutated and control mice. A decrease in the immunohistochemical labeling intensity with tyrosine hydroxylase was observed in the superior cervical ganglion (SCG), as well as with the pontine nucleus locus 4′-Ethynyl-2′-deoxyadenosine coeruleus, and the sympathetic innervation of blood vessels and glands in the head was significantly decreased. None of the brain nuclei 4′-Ethynyl-2′-deoxyadenosine analyzed exhibited any significant decreases in the total quantity of neurons, but the packing denseness of neurons in the nucleus locus coeruleus was decreased. These data show that GDNF might be one neurotrophic element that contributes to the development of central and peripheral noradrenergic neurons. (Buj-Bello et al., 1995;Ebendal et al., 1995). Consequently, potential alterations of these constructions were also evaluated. The following specific questions were resolved in the present study. (1) Are there alterations in transmitter synthetic enzymes in dopaminergic, noradrenergic, or cholinergic neurons in the brain? (2) Are there alterations in tyrosine hydroxylase staining in SCG? (3) Does a null mutation of the GDNF gene result in disturbances in tooth germ or taste bud development? MATERIALS AND METHODS immunoreactivity. For details on immunohistochemical techniques, observe Granholm et al. (1994). test for assessment of means. In addition to the cell counts, optical staining densities were obtained from sections incubated with TH or ChAT antibodies. Unaltered images were acquired with the 10 objective, and background was subtracted using nonstained portions of the section. Thereafter, the entire area of the nucleus was traced, and optical densities were from five sections in each nucleus. The ideals are offered as background-to-staining ratios. The same image analysis system was used to determine the size and thickness of incisors and molars as well as enamel and pulp width in developing teeth of GDNF +/+ and ?/? animals. The range of ideals was arranged by a scale pub in the eye piece of the microscope. RESULTS Gastrointestinal?system As has been reported previously by us as well as others (Moore et al., 1996; Pichel et al., 1996; Sanchez et al., 1996), the GDNF?/? animals exhibited a severe disturbance in the development of the gastrointestinal tract. Number ?Number11 depicts the gross appearance of the belly in a newborn GDNF ?/? animal (Fig.?(Fig.11= 3 per group. Open in a separate windows Fig. 3. Incisors (and are from ?/? animals, and and are from +/+ animals. Note the decrease in innervation, both in the blood vessel and in the respiratory mucosal lining, in the ?/? animals, compared with settings. Scale pub (demonstrated in = 3), and in the +/+ group it was 63 5 (= 4) cells per 100,000 m2. The mean background/staining percentage in the substantia nigra of GDNF ?/? mice was 1.5 0.2 and in the +/+ group 1.4 0.05. The average cell body size of TH-immunoreactive neurons in the substantia nigra was also related between the two organizations. The mean cell size in the GDNF ?/? GATA3 group was 120 16% of settings (= 3). Open in a separate windows Fig. 6. Substantia nigra sections incubated with TH antibodies. (Arenas et al., 1994) and (Friedman et al., 1993). Central cholinergic neurons, primarily the motoneurons of the midbrain cranial nerve nuclei, have also been shown to be affected by GDNF treatment. GDNF was found to increase the activity of ChAT in ethnicities from rat mesencephalon, and facial nerve axotomy resulted in a 50% decrease in motoneuron degeneration if GDNF was applied (Zurn et al., 1994; Yan et al., 1995). These earlier results motivated us to carry out a more generalized investigation of the effects of lack of GDNF during early development in both PNS and CNS..