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Serum Insulin-like System Alterations in Patients with Spinocerebellar Ataxia

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Tutor: DongChunBo
School: Dalian Medical University
Course: Neurology
Keywords: SCA,family of insulin-like growth factors,insulin-like growth factor1,insulin-li
CLC: R744.7
Type: Master's thesis
Year:  2013
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objective: family of insulin-like growth factors including insulin-like growth factors、insulin-like growth factor binding protein and insulin have important role in celldevelopment, differentiation in nervous system and also have potency forneuroprotective. Hereditary spinocerebellar ataxias (SCAs) constitute a group ofautosomal dominant neurodegenerative disorder. The most common SCAs are causedby CAG glutamine trinucleotide repeat expansion. Because of Involving thecerebellum、brainstem、Spinal cord, SCA is characterized by the development ofimpairment of equilibrium and gait, slowness of voluntary movements,scanningspeech,intention tremor,nystagmus,sensory disturancbe.We aimed to investigate thebiomarker profile of serum insulin-like growth factors components in SCA3,considering their relationship with age of onset, course of disease,gender, BMI,clinicaland molecular.Object and methods:The research objects from Dalian, Liaoning Province aremembers of nine families whose clinical diagnoses conformed to Harding standards. Wevisited these families and collected details through interrogation and neurologicalspecialist examination to these patients. And clinical status of each patient wasestimated by the International Cooperative Ataxia Rating Scale (ICARS). We made thegene testing for the part of members form the nine families to determine the types ofSCA patients and CAG repeat number.。A case–control study was performed between2011and2012with20molecularly confirmed SCA patients and25healthy, nonrelatedindividuals with similar age, gender, and environmental characteristics。We makecomparison of Serum IGF-1, IGFBP-3insulin which was determined byelectrochemiluminescence between case and control. Correlation analysis was acceptedamong the correlation course of disease, age of onset, course of disease, gender, BMI,assessment for the average of scores of ICARS and CAG repeat number. Statistical significance was defined as P <0.05。Result:IGF-1levels were lower in SCA patients than in controls (P=0.008) andIGFBP3levels were also lower in SCA patients than in controls (P=0.029). An indirectmeasure of free IGF-1levels, the IGF1:IGFBP3molar ratio (P=0.029, corrected by BMIand age). But we found no differences in serum Ins levels between SCA patients andcontrols (P=0.171). Correlation analysis was accepted among the correlation course ofdisease, age of onset, course of disease, gender, BMI, assessment for the average ofscores of ICARS and CAG repeat number. Serum IGF1level were correlatedsignificantly with the course of disease(r=0.493、0.497P=0.027),and also wasassociated BMI (r=-0.853P=0.001).But serum IGF1level did not correlate withgender(p=0.107)、age of onset(r=-0.001p=0.998)、gene repeat number(r=0.212p=0.37)and the average of scores of ICARS(r=-0.222p=0.347)。In the meanwhile,serum IGFBP3level were also correlated significantly with the course of disease(r=0.497P=0.026),and also was associated BMI (r=-0.693, P=0.001). Andserum IGFBP3level did not correlate with gender(p=0.295)、age of onset (r=0.014,p=0.925)、gene repeat number(r=-0.081p=0.735)and the average of scores of ICARS(r=-0.198p=0.403). Serum Ins level were correlated significantly with the averageof scores of ICARS (r=-0.572p=0.017). But serum INS did not correlate with gender(p=0.199)、age of onset(r=0.333p=0.151)、course of disease(r=0.189p=0.426)、BMI(r=-0.39p=0.089) and gene repeat number(r=0.224p=0.342). Serum IGF-1correlated positively with both IGFBP-3and Ins (r=0.635、0.451, P=0.003、0.046),while there were no correlation between IGFBP-3and Ins.Conclusion:1.serum IGF-1、GFBP-3in SCA patients were significantly lower thancontrols because of decreasing on central and peripheral level of IGF-1, therefore IGF-1and IGF-3can be used as indicator to estimate brain damage in SCA but not to reflectthe degree of it.2. We estimate that the intracerebral free IGF-1in SCA mightdecrease, for an indirect measure of serum free IGF-1levels (the IGF1:IGFBP3molarratio) was lower in SCA than the controls3. There were no difference between serumInsulin in SCA patients and in controls, but serum Ins level were correlated significantlywith the average of scores of ICARS. We infer that as the development of the disease,serum Ins might be decrease.4. As Serum IGF-1correlated positively with both IGFBP-3and Ins, they can influence synergistically on nervous system.
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