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Biomedical subjects

R E Frischer

Publications and source records attributed to R E Frischer.

4 recordsLinked to original sources

ACTH peptides stimulate motor nerve sprouting in development.

Maturational changes at the neuromuscular junction (nmj) of rat neonates were studied using scanning electron microscopy and light microscopy that permitted quantification of muscle fiber diameter, length of nerve terminal branching, end-plate area, and perimeter. Administration of ACTH 4-10 (10 micrograms/kg s.c. daily from day of birth) stimulated nerve terminal branching, an effect most evident in 14-day-old pups. The trisubstituted derivative of ACTH 4-9 (Org 2766) when administered at 0.01 microgram/kg/daily, had a more potent effect, increasing end-plate perimeter and nerve terminal branching on the first postnatal week and markedly increasing only nerve terminal branching at 14 days of age. This is a dose-responsive action since 10 micrograms/kg/daily severely inhibits nerve sprouting. By 21 days, there were no differences between peptide- and saline-treated neonates. Peptide-induced sprouting was elicited only in the first 2 weeks of postnatal life. This time course corresponds with the critical period for nmj maturation and ceases when polyneuronal innervation of muscle fibers also terminates. It is suggested that ACTH peptides may exert a physiological role on nerve sprouting during development.

Adrenocorticotropic Hormone↗

Maturational changes in neonatal rat motor system with early postnatal administration of nicotine.

Experiments were designed to assess the effects of chronic maximum 'smoking dose' nicotine administration on neonatal motor behavior and neuromuscular structural maturation. Thus, Sprague-Dawley rat neonates received daily subcutaneous injections of nicotine (0.05 mg/kg/day) from postnatal days 1 to 14. Motor behavior (ambulations, stop and go movements) was not affected, but a marked increase in grasping duration resulted, indicating increased neuromuscular maturation. Concomitantly, neuromuscular morphological and dynamic contractile changes were observed in the in situ extensor digitorum longus (EDL) muscle. The EDL muscle showed accelerated morphological dimensions of the endplate at postnatal day 7 and a more rapid twitch at 2 weeks of age. The results suggest that this maximum 'smoking dose' of nicotine induces time-dependent maturational changes in the neuromuscular model.

Animals↗

ACTH peptides as organizers of neuronal patterns in development: maturation of the rat neuromuscular junction as seen by scanning electron microscopy.

SEM was used to visualize the normal postnatal development of the neonatal rat neuromuscular junction (nmj). Maturational changes evoked by ACTH/MSH 4-10 (10 micrograms/kg/day IP) or ACTH/MSH 4-9 (Org 2766) (0.01 microgram/kg/day IP) were compared to controls and to pups treated with nicotine during prenatal and postnatal life, or only during the gestation period. Pregnant females received 0.25 mg/kg 2X daily IP; neonates 0.05 mg/kg/day SC. The Desaki and Uehara and Fahim et al. methods revealed the nmj on the extensor digitorum muscle to be covered by a delicate drapery of postjunctional folds that surround the immature endplate region. By the second week of postnatal life, these folds become more complex and cover a larger area. Upon maturation the folds descend and invaginate into the muscle fiber. Peptide treatment with either ACTH/MSH 4-10 or ACTH/MSH 4-9 accelerates maturation of the endplate as demonstrated by the increased convolutions of the folds. Similar effects follow nicotine administration. The observed changes in morphology of the developing nmj subjected to nicotine may be mediated through nicotine-evoked ACTH release.

Adrenocorticotropic Hormone↗

Neonatal neuromuscular parameters vary in susceptibility to postnatal ACTH/MSH 4-10 administration.

Neonatal Sprague-Dawley rats administered the fragment of adrenocorticotropic hormone ACTH/MSH 4-10 (10 micrograms/kg/daily, SC) postnatally, show marked differences in the plasticity of the functional and morphological parameters of their neuromuscular system. Initial contraction durations of the immature fast muscle, extensor digitorum longus (EDL), are shorter than saline-treated controls indicating accelerated development. Qualitative studies of the developing EDL neuromuscular junctions as viewed by the scanning electron microscope and quantitative analysis permitted by light microscopy confirms that ACTH/MSH 4-10 affects the maturation of the endplate region. Motor behavior of rat pups demonstrates an age-related difference in the susceptibility to this peptide fragment; one week old neonates showing no response to ACTH/MSH 4-10, two week old pups showing an increase in motor activity. The results indicate that while the developing neuromuscular system is sensitive to the input of ACTH/MSH peptide treatment, this susceptibility is age-related.

Adrenocorticotropic Hormone↗