gastrin-releasing-peptide and Spinal-Cord-Injuries

Spinal cord injury (SCI) causes sexual dysfunction, including anejaculation in men. Likewise, chronic mid-thoracic contusion injury impairs ejaculatory reflexes in male rats. Ejaculation is controlled by a spinal ejaculation generator (SEG) comprised of a population of lumbar spinothalamic (LSt) neurons. LSt neurons co-express four neuropeptides, including gastrin-releasing peptide (GRP) and galanin and control ejaculation via release of these peptides in lumbar and sacral autonomic and motor nuclei. Here, we tested the hypothesis that contusion injury causes a disruption of the neuropeptides that are expressed in LSt cell bodies and axon terminals, thereby causing ejaculatory dysfunction. Male Sprague Dawley rats received contusion or sham surgery at spinal levels T6-7. Five to six weeks later, animals were perfused and spinal cords were immunoprocessed for galanin and GRP. Results showed that numbers of cells immunoreactive for galanin were not altered by SCI, suggesting that LSt cells are not ablated by SCI. In contrast, GRP immunoreactivity was decreased in LSt cells following SCI, evidenced by fewer GRP and galanin/GRP dual labeled cells. However, SCI did not affect efferent connections of LSt, cells as axon terminals containing galanin or GRP in contact with autonomic cells were not reduced following SCI. Finally, no changes in testosterone plasma levels or androgen receptor expression were noted after SCI. In conclusion, chronic contusion injury decreased immunoreactivity for GRP in LSt cell soma, but did not affect LSt neurons per se or LSt connections within the SEG. Since GRP is essential for triggering ejaculation, such loss may contribute to ejaculatory dysfunction following SCI.

Topics: Animals; Chronic Disease; Ejaculation; Gastrin-Releasing Peptide; Locomotion; Male; Rats; Rats, Sprague-Dawley; Sexual Dysfunction, Physiological; Spinal Cord Injuries; Thoracic Vertebrae

Experimental animal study.. Although a population of gastrin-releasing peptide (GRP) neurons in the lumbar spinal cord has an important role in erection and ejaculation in rats, little information exists on this GRP system in primates. To identify the male-specific GRP system in the primate spinal cord, we studied the lumbosacral cord in macaque monkeys as a non-human primate model.. University laboratory in Japan.. To determine the gene sequence of GRP precursors, the rhesus macaque monkey genomic sequence data were searched, followed by phylogenetic analysis. Subsequently, immunocytochemical analysis for GRP was performed in the monkey spinal cord.. We have used bioinformatics to identify the ortholog gene for GRP precursor in macaque monkeys. Phylogenetic analysis suggested that primate prepro-GRP is separated from that of other mammalian species and clustered to an independent branch as primates. Immunocytochemistry for GRP further demonstrated that male-dominant sexual dimorphism was found in the spinal GRP system in monkeys as in rodents.. We have demonstrated in macaque monkeys that the GRP system in the lower spinal cord shows male-specific dimorphism and may have an important role in penile functions not only in rodents but also in primates.. Tissues of Nihonzaru (Japanese macaque monkeys) were provided in part by National Institutes of Natural Sciences (NINS) through the National Bio-Resource Project (NBRP) of the MEXT, Japan. This work was supported in part by KAKENHI from the Japan Society for the Promotion of Science (JSPS) (to KT; 15KK0343, 15J40220 and HS; 15K15202, 15KK0257, 15H05724).

Topics: Animals; Biological Evolution; Disease Models, Animal; Erectile Dysfunction; Female; Gastrin-Releasing Peptide; Humans; Macaca; Male; Nitric Oxide Synthase Type I; Penile Erection; Sex Characteristics; Spinal Cord; Spinal Cord Injuries

Neural progenitor cell (NPC) transplantation is a promising therapeutic strategy for spinal cord injury (SCI) because of the potential for cell replacement and restoration of connectivity. Our previous studies have shown that transplants of NPC, composed of neuron- and glia-restricted progenitors derived from the embryonic spinal cord, survived well in partial lesion models and generated graft-derived neurons, which could be used to form a functional relay. We have now examined the properties of a similar NPC transplant using a complete transection model in juvenile and adult rats. We found poor survival of grafted cells despite using a variety of lesion methods, matrices, and delays of transplantation. If, instead of cultured progenitor cells, the transplants were composed of segmental or dissociated segments of fetal spinal cord (FSC) derived from similar-staged embryos, grafted cells survived and integrated well with host tissue in juvenile and adult rats. FSC transplants differentiated into neurons and glial cells, including astrocytes and oligodendrocytes. Graft-derived neurons expressed glutaminergic and GABAergic markers. Grafted cells also migrated and extended processes into host tissue. Analysis of axon growth from the host spinal cord showed serotonin-positive fibers and biotinylated dextran amine-traced propriospinal axons growing into the transplants. These results suggest that in treating severe SCI, such as complete transection, NPC grafting faces major challenges related to cell survival and formation of a functional relay. Lessons learned from the efficacy of FSC transplants could be used to develop a therapeutic strategy based on neural progenitor cells for severe SCI.

Topics: Age Factors; Animals; Cell Differentiation; Cell Movement; Cell Proliferation; Choline O-Acetyltransferase; Disease Models, Animal; Embryo, Mammalian; Female; Gastrin-Releasing Peptide; Nerve Regeneration; Nerve Tissue Proteins; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Rats, Transgenic; Serotonin; Spinal Cord Injuries; Stem Cell Transplantation; Stem Cells