2012年10月18日 訊 /生物谷BIOON/ --近日,，來自波士頓大學(xué)醫(yī)學(xué)院的研究者在亨廷頓氏疾病對(duì)大腦損傷效應(yīng)的研究上取得了新的進(jìn)展,，相關(guān)研究成果刊登于國(guó)際著名雜志Neurology上,，這項(xiàng)研究主要揭示了受亨廷頓氏病影響較大的大腦區(qū)域,，同時(shí)為開辟新型的療法帶來了幫助,。
亨廷頓?。℉D）是一種遺傳性的致死性神經(jīng)性障礙疾病,，當(dāng)個(gè)體在40歲左右時(shí)常常會(huì)被診斷出該疾病,，在1993年研究者鑒別出了該疾病的致病基因，但是其導(dǎo)致特定神經(jīng)元或腦細(xì)胞死亡的原因目前尚不清楚,。
這項(xiàng)研究中,，研究者對(duì)來自HD患者的664份大腦樣品進(jìn)行了研究，他們對(duì)受到HD影響的超過50個(gè)神經(jīng)元區(qū)域進(jìn)行了研究分析,，結(jié)合對(duì)亨廷頓基因的特異性突變體的遺傳學(xué)研究,，研究者們分析了來自病人的臨床神經(jīng)學(xué)信息?；谏鲜龇治?，研究者發(fā)現(xiàn)了HD影響大腦主要表現(xiàn)在大腦的兩個(gè)區(qū)域上，紋狀體,，其位于大腦深層,，參與運(yùn)動(dòng)控制和不自主運(yùn)動(dòng)，是受到HD影響最嚴(yán)重的區(qū)域,；外部周質(zhì)區(qū)主要參與認(rèn)知功能和思維處理過程,，其也受到HD的損傷，但是相比紋狀體,，損傷較輕,。
于此同時(shí)研究者在不同的大腦區(qū)域細(xì)胞死亡過程中發(fā)現(xiàn)了特定的遺傳突變，比如,，某些個(gè)體會(huì)出現(xiàn)嚴(yán)重的大腦外皮退化等,。研究者M(jìn)yers表示，當(dāng)僅僅有一種遺傳突變引發(fā)亨廷頓氏癥時(shí),，疾病就會(huì)以不同方式在不同人群中影響其大腦不同的區(qū)域,，首先，我們會(huì)測(cè)定這些變化,，希望鑒別出在特殊個(gè)體中發(fā)生這種病變的原因并且去預(yù)防它,。
目前研究者開始進(jìn)行大范圍深入研究,，來尋找保護(hù)HD患者神經(jīng)元的特定基因或者其它影響因子的方法，研究者希望這些保護(hù)性因子可以為未來HD的療法帶來幫助,。（生物谷Bioon.com）
編譯自：Pathology of Huntington's Disease Identified
doi:10.1212/WNL.0b013e31826e9a5d
PMC:
PMID:
Assessment of cortical and striatal involvement in 523 Huntington disease brains
Tiffany C. Hadzi, MPH, Audrey E. Hendricks, PhD, Jeanne C. Latourelle, DSc, Kathryn L. Lunetta, PhD, L. Adrienne Cupples, PhD, Tammy Gillis, BSc, Jayalakshmi Srinidhi Mysore, BSc, James F. Gusella, PhD, Marcy E. MacDonald, PhD, Richard H. Myers, PhD* and Jean-Paul Vonsattel, MD*
Objective: To evaluate the relationship of striatal involvement in Huntington disease (HD) to involvement in other brain regions, CAG repeat size, onset age, and other factors. Methods: We examined patterns of neuropathologic involvement in 664 HD brains submitted to the Harvard Brain Tissue Resource Center. Brains with concomitant Alzheimer or Parkinson changes (n = 82), more than 20% missing data (n = 46), incomplete sample submission (n = 12), or CAG repeat less than 36 (n = 1) were excluded, leaving 523 cases. Standardized ratings from 0 (absent) to 4 (severe) of gross and microscopic involvement were performed for 50 regions. Cluster analysis reduced the data to 2 main measures of involvement: striatal and cortical. Results: The clusters were correlated with each other (r = 0.42) and with disease duration (striatal: r = 0.35; cortical: r = 0.31). The striatal cluster was correlated with HD repeat size (r = 0.50). The cortical cluster showed a stronger correlation with decreased brain weight (r = −0.52) than the striatal cluster (r = −0.33). The striatal cluster was correlated with younger death age (r = −0.31) and onset age (r = −0.46) while the cortical cluster was not (r = 0.09, r = −0.04, respectively). Conclusions: The 2 brain clusters had different relationships to the HD CAG repeat size, onset age, and brain weight, suggesting that neuropathologic involvement does not proceed in a strictly coupled fashion. The pattern and extent of involvement varies substantially from one brain to the next. These results suggest that regional involvement in HD brain is modified by factors which, if identified, may lend insight into novel routes to therapeutics.
