Experimental scoliosis in melatonin-deficient C57BL/6J mice without pinealectomy (original) (raw)
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Role of melatonin deficiency in the development of scoliosis in pinealectomised chickens
The Journal of Bone and Joint Surgery. British volume, 1995
We studied the possible role of melatonin deficiency in experimentally-induced scoliosis. A total of 90 chickens underwent pinealectomy on the third day after hatching: 30 were treated with serotonin, 30 with melatonin and 30 received no therapy (control group). Scoliosis developed in all the control group, in 22 of the serotonin group, and in only 6 of the melatonin group. The six melatonin-treated chickens with scoliosis had less severe spinal deformities than those in the serotonin-treated group. There were lower blood melatonin concentrations in chickens with scoliosis than in those without. Our findings suggest that melatonin deficiency contributes to the aetiology of this experimental scoliosis, probably by interfering with the normally symmetrical growth of the proprioceptive system involving the paraspinal muscles and the spine.
Spine, 2003
Study Design. This study was designed to compare the effect of suppression of melatonin secretion by bright light in chickens with that of surgical pinealectomy. Objective. To determine whether suppression of melatonin secretion without surgery in chickens can result in scoliosis development. Summary of Background Data. Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis. Conversely, cutting of the pineal stalk without removal of the pineal gland will also result in scoliosis. This study addresses the question of whether constant bright light can induce scoliosis formation, because it is well known that 24-hour bright lighting conditions can suppress the secretion of melatonin to an equivalent level as pinealectomy. Materials and Method. Seventy-seven newborn Nihon chickens were separated into three groups. A control group (n ϭ 21) with no surgery performed; a pinealectomy group (n ϭ 15) that served as surgical controls; and a constant light group (n ϭ 41). The first two groups were kept together in a strict 12-hour light-dark cycle, whereas the third group was separately kept with constant lighting conditions (Ͼ100 lux). All the chickens were radiographed at two weekly intervals, and blood was taken during the middle of the light and dark cycles for serum melatonin assay using ELISA. Results. Fifty-four percent of the pinealectomized chickens had scoliosis develop by 6 weeks. None of the constant-light chickens or controls had scoliosis develop for up to 11 weeks. Measurements of serum melatonin levels of the constant light group confirm that secretion is suppressed. Conclusion. This study suggests that for scoliosis to develop in chickens, the surgical operation itself is important and challenges the role of melatonin as an isolated etiological factor in the development of scoliosis.
International journal of molecular sciences, 2014
Adolescent idiopathic scoliosis (AIS) is a common orthopedic disorder of unknown etiology and pathogenesis. Melatonin and melatonin pathway dysfunction has been widely suspected to play an important role in the pathogenesis. Many different types of animal models have been developed to induce experimental scoliosis mimicking the pathoanatomical features of idiopathic scoliosis in human. The scoliosis deformity was believed to be induced by pinealectomy and mediated through the resulting melatonin-deficiency. However, the lack of upright mechanical spinal loading and inherent rotational instability of the curvature render the similarity of these models to the human counterparts questionable. Different concerns have been raised challenging the scientific validity and limitations of each model. The objectives of this review follow the logical need to re-examine and compare the relevance and appropriateness of each of the animal models that have been used for studying the etiopathogenesi...
European Spine Journal, 2003
Pinealectomy frequently produces spinal deformity in some animal models, but the precise biological mechanism of this phenomenon remains obscure. The current study investigated the effects of an autograft pineal body on the development of spinal deformity and serum melatonin (MLT) concentration after pinealectomy in the chicken. Thirty-six chickens (2 days of age) were divided into three equal groups. While the removal of the pineal gland was performed in groups B and C, a pineal body autograft was surgically implanted into the body wall musculature only in the pineal transplantation group (group C). Chickens in which no surgical intervention was performed served as intact controls (group A). Posteroanterior radiographs of the spines of the chickens were taken at the age of 8 weeks. These were used to determine Cobb angles and to measure the rib-vertebra angles (RVA) on the concave and convex sides of the curves, from which data the difference between the convex and concave RVA (the RVAD) was calculated. At the end of the study, serum MLT levels were determined using the enzyme-linked immunosorbent assay method, and histopathological examination of specimens from all the groups was performed. The results were compared using one-way analysis of variance followed by Duncan's test for pairwise comparisons or by the Kruskal-Wallis test followed by the Mann-Whitney U tests for comparisons between two groups. In this study, the serum MLT levels in groups B and C were significantly lower than those in group A (P<0.05). However, scoliosis developed in only 7 of 12 (58%) in group B and 6 of 12 (50%) in group C. The average Cobb angle and RVAD in groups B and C were significantly larger than those found in group A (P=0.000 and P=0.001, respectively). Interestingly, there were no significant differences in either serum MLT levels or development of scoliosis between groups B and C. From the results of the current study, it is evident that the intramuscular pineal gland transplantation following pinealectomy in young Hybro Broiler chickens has no significant effect on the development of spinal deformity and serum MLT level. In the light of this result, the role of MLT in the development of spinal deformity in chickens after pinealectomy remains controversial, and further investigations are warranted.
Melatonin and adolescent idiopathic scoliosis
The Journal of Bone and Joint Surgery, 2000
S coliosis seen in the chicken after pinealectomy resembles adolescent idiopathic scoliosis in man. It has been suggested that in both species, deficiency of the pineal hormone, melatonin, is responsible for this phenomenon. In nine patients with adolescent idiopathic scoliosis and in ten age-and gender-matched controls, the circadian levels of serum melatonin and the excretion of urinary 6-hydroxy-melatonin-sulphate, the principal metabolite of melatonin, were determined. There were no statistically significant differences in the secretion of serum melatonin or the excretion of urinary 6-hydroxy-melatonin-sulphate between the patients and the control group. The hypothesis of melatonin deficiency as a causative factor in the aetiology of adolescent idiopathic scoliosis cannot be supported by our data.
The Effect of Pinealectomy on Scoliosis Development in Young Nonhuman Primates
Spine, 2005
Study Design. Prospective study on pinealectomy in primates. Objective. To evaluate whether pinealectomy in a bipedal nonhuman primate model will result in the development of scoliosis. Summary of Background Data. Pinealectomy in newborn chickens consistently resulted in scoliosis development. Published data suggest that the surgical removal of the pineal, loss of melatonin secretion, and a bipedal posture are important elements in the development of scoliosis in lower animal models. Method. There were 18 rhesus monkeys between 8 and 11 months old that underwent pineal excision. All monkeys were kept in a regulated 12-hour light-dark cycle. Monthly radiographs assessed scoliosis development. Completeness of pineal excision was assessed by measurement of a major metabolite of melatonin in the urine, 6-sulfatoxymelatonin, using an enzyme-linked immunosorbent assay assessed. Results. Mean follow-up was 28 months (range 10Ϫ 41). Seven monkeys died prematurely, and 11 survived to date; the data from those that died could still be used, although follow-up was shortened. At the latest follow-up or death, scoliosis did not develop in any of the monkeys. Urinary 6-sulfatoxymelatonin measurements revealed 3 patterns. Group 1 consisted of 10 monkeys, which showed definite evidence of complete pineal excision. Group 2 consisted of an uncertain group of 2 monkeys in which the nighttime melatonin level is slightly high. Group 3 consisted of 6 monkeys that had incomplete pineal excision or ectopic melatonin production. Conclusions. To our knowledge, this is the first report of pinealectomy in nonhuman primates. Of the 18 monkeys, 10 had a loss of melatonin secretion, for a mean of 29 months after surgery. Because none of the monkeys had scoliosis develop, this study strongly suggests that the possible etiologic factors producing idiopathic scoliosis in lower animals are different from primates, and findings in lower animals cannot necessarily be extrapolated to human beings.
Scoliosis, 2007
Session 1 5:00-6:30 p.m. Interactive poster session and social reception Bialek M. Functional Individual Therapy of Scoliosis -FITS Botens-Helmus C, Klein R, Stephan C, Hans-Rudolf Weiss. Reliability of the Bad Sobernheim Stress Questionnaire (BSSQbrace) Brooks WJ, Krupinski EA, Hawes MC. Reversal of curvature magnitude in response to physical methods: a 15year followup in an adult female diagnosed with moderately severe scoliosis at age eleven. Correia KA, Megna J. The effect of physical therapy on computerized dynamic posturography of an adolescent with idiopathic scoliosis: A case study. Durmala J. 'Dobosiewicz's method Ferguson L. An artist's inquiry into scoliosis. Karski T, Kalakucki J, Karski J. Patient-specific exercise programs in the conservative management of the so-called idiopathic scoliosis Maruyama T. 'Short and long term objectives of conservative management of IS''. Miller E. Yoga for scoliosis: an adult case approach. Monroe M. Yoga and Somatic Therapy for the treatment of adolescent idiopathic scoliosis: Adult case report. Negrini S. The evidence based ISICO approach to rehabilitation of spinal deformities. Nieh MT. Exercise-based methods to treat adult scoliosis: a case report. Rensselaer NY. O'Brien JP. Retrospective review of a single case of surgically treated AIS over a 40-year period. Rigo M. Conservative approach for the treatment of idiopathic scoliosis in the ' E. Salva Institute' of Barcelona Shawafaty N, Cheriet F, Coillard C, Rhalmi S, Labelle H, Rivard CH. Non invasive evaluation of SpineCor brace correction from surface topography Sherman K. Pilot Study to Validate a Scoliosis-Specific Instrument that Measures Quality of Life and Treatment Effect. Stokes IAF. Analysis and simulation of progressive adolescent scoliosis by biomechanical growth modulation Torres B. Katharina Schroth Method for treatment of post-polio scoliosis in an adult.
Melatonin the "light of night" in human biology and adolescent idiopathic scoliosis
Scoliosis, 2007
Melatonin &amp;amp;amp;quot;the light of night&amp;amp;amp;quot; is secreted from the pineal gland principally at night. The hormone is involved in sleep regulation, as well as in a number of other cyclical bodily activities and circadian rhythm in humans. Melatonin is exclusively involved in signalling the &amp;amp;amp;#39;time of day&amp;amp;amp;#39; and &amp;amp;amp;#39;time of year&amp;amp;amp;#39; (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body&amp;amp;amp;#39;s chronological pacemaker or &amp;amp;amp;#39;Zeitgeber&amp;amp;amp;#39;. The last decades melatonin has been used as a therapeutic chemical in a large spectrum of diseases, mainly in sleep disturbances and tumours and may play a role in the biologic regulation of mood, affective disorders, cardiovascular system, reproduction and aging. There are few papers regarding melatonin and its role in adolescent idiopathic scoliosis (AIS). Melatonin may play a role in the pathogenesis of scoliosis (neuroendocrine hypothesis) but at present, the data available cannot clearly support this hypothesis. Uncertainties and doubts still surround the role of melatonin in human physiology and pathophysiology and future research is needed.
Melatonin Signaling Dysfunction in Adolescent Idiopathic Scoliosis
Spine, 2004
Study Design. In vitro assays were performed with bone-forming cells isolated from 41 patients with adolescent idiopathic scoliosis and 17 control patients exhibiting another type of scoliosis or none. Objective. To determine whether a dysfunction of the melatonin-signaling pathway in tissues targeted by this hormone is involved in adolescent idiopathic scoliosis. Summary of Background Data. Pinealectomy in chicken has led to the formation of a scoliotic deformity, thereby suggesting that a melatonin deficiency may be at the source of adolescent idiopathic scoliosis. However, the relevance of melatonin in the etiopathogenesis of that condition is controversial because most studies have reported no significant change in circulating levels of melatonin in patients with adolescent idiopathic scoliosis. Methods. Primary osteoblast cultures prepared from bone specimens obtained intraoperatively during spine surgeries were used to test the ability of melatonin and Gpp(NH)p, a GTP analogue, to block cAMP accumulation induced by forskolin. In parallel, melatonin receptor and Gi protein functions were evaluated by immunohistochemistry and by coimmunoprecipitation experiments. Results. The cAMP assays demonstrated that melatonin signaling was impaired in osteoblasts isolated from adolescent idiopathic scoliosis patients to different degrees allowing their classification in 3 distinct groups based on their responsiveness to melatonin or Gpp(NH)p. Conclusion. Melatonin signaling is clearly impaired in osteoblasts of all patients with adolescent idiopathic scoliosis tested. Classification of patients with adolescent idiopathic scoliosis in 3 groups based on functional in vitro assays suggests the presence of distinct mutations interfering with the melatonin signal transduction. Posttranslational modifications affecting Gi protein function, such as serine residues phosphorylation, should be considered as one possible mechanism in the etiopathogenesis of AIS.