RESUMEN
Single ligature nerve constriction (SLNC) of the rat sciatic nerve triggers neuropathic pain-related behaviors and induces changes in neuropeptide expression in primary afferent neurons. Bone marrow stromal cells (MSCs) injected into the lumbar 4 (L4) dorsal root ganglia (DRGs) of animals subjected to a sciatic nerve SLNC selectively migrate to the other ipsilateral lumbar DRGs (L3, L5 and L6) and prevent mechanical and thermal allodynia. In this study, we have evaluated the effect of MSC administration on the expression of the neuropeptides galanin and NPY, as well as the NPY Y(1)-receptor (Y(1)R) in DRG neurons. Animals were subjected to a sciatic nerve SLNC either alone or followed by the administration of MSCs, phosphate-buffered saline (PBS) or bone marrow non-adherent mononuclear cells (BNMCs), directly into the ipsilateral L4 DRG. Seven days after injury, the ipsilateral and contralateral L4-5 DRGs were dissected out and processed for standard immunohistochemistry, using specific antibodies. As previously reported, SLNC induced an ipsilateral increase in the number of galanin and NPY immunoreactive neurons and a decrease in Y(1)R-positive DRG neurons. The intraganglionic injection of PBS or BNMCs did not modify this pattern of expression. In contrast, MSC administration partially prevented the injury-induced changes in galanin, NPY and Y(1)R expression. The large number of Y(1)R-immunoreactive neurons together with high levels of NPY expression in animals injected with MSCs could explain, at least in part, the analgesic effects exerted by these cells. Our results support MSC participation in the modulation of neuropathic pain and give insight into one of the possible mechanisms involved.
Asunto(s)
Galanina/biosíntesis , Neuropéptido Y/biosíntesis , Receptores de Neuropéptido Y/biosíntesis , Nervio Ciático/lesiones , Células del Estroma/fisiología , Animales , Células de la Médula Ósea , Constricción Patológica/metabolismo , Ratas , Neuropatía Ciática , Trasplante de Células Madre , Resultado del Tratamiento , Heridas y Lesiones/metabolismoRESUMEN
The immunohistochemical distribution of galanin (Gal) in the brain and pituitary of Rhinella arenarum was studied during development. Gal-immunoreactivity was first observed in the brain just after hatching in anterior preoptic area, infundibular area, median eminence and pars distalis of the pituitary as well as in the olfactory epithelium. At the beginning of prometamorphosis new Gal-immunoreactive (ir) cells were observed in the olfactory nerve and bulb. Later in prometamorphosis new Gal-ir cells were observed in the telencephalon, suprachiasmatic nucleus, rostral rhombencephalon and in the pars nervosa of the pituitary. The most numerous accumulations of Gal-ir neurons throughout the larval development were observed in the ventral hyphothalamus where numerous Gal-ir cells of cerebrospinal fluid-contacting type were found. During metamorphic climax and soon after we did not detect Gal-ir neurons in the pallium, medial or pretectal dorsal thalamus. In the median eminence and pars distalis of the pituitary many Gal-ir fibers were found during development indicating that Gal may play a role in the modulation of hypophyseal secretion. Furthermore, the distribution of Gal-ir elements observed throughout larvae development indicates that galaninergic system maturation continues until sexual maturity.
Asunto(s)
Anuros , Encéfalo/metabolismo , Galanina/biosíntesis , Hipófisis/metabolismo , Animales , Encéfalo/citología , Encéfalo/crecimiento & desarrollo , Inmunohistoquímica , Larva/citología , Larva/crecimiento & desarrollo , Larva/metabolismo , Microscopía Electrónica de Rastreo , Hipófisis/citología , Hipófisis/crecimiento & desarrolloRESUMEN
Galanin is a 29 amino-acid peptide originally isolated from porcine intestine. It is synthesized as part of a large precursor peptide the preprogalanin. Immunological studies has showed that there is interspecies conservation of the N terminal portion although the C-terminal portions has a little of immunoreactivity. Galanin has a number of pharmacological properties in whole animals and isolated tissues. Galanin contracts isolated preparation from rat fundus, ileum, colon and urinary bladder. Direct administration of galanin (pGal) into the rat third ventricule stimulates food intake, increases plasma growth hormone and prolactin levels and decrease dopamine levels in the median eminence. Intravenous infusion in dog and humans induce a hyperglycemia and glucose intolerance and inhibits the insulin, somatostatin and pancreatic polipeptide secretion from pancreas. Galanin is a estrogen-stimulated peptide. Estrogens increase dramatically the synthesis of their mRNA and the peptide in the rat pituitary. Galanin-like immunoreactivity is widely distributed in several mamalian species including humans. In the central nervous system it was found in medium emminence, hypothalamus, arcuate nucleus etc. Its localization in neurosecretory granules suggest that galanin functions as a neurotransmitter. The detection of a Gal-immunorectivity in the plasma after 17 beta estradiol stimulation suggests that galanin has a distal target and therefore, may be an additional anterior pituitary hormone. Galanin has been localized in reproductive tissues and this suggests that it may play an estrogen mediated role in the hypothalamic and pituitary function. However, the molecular mechanisms involved in their function remain to be studied.