We would like to thank Dr. Harry Orr at the University of Minnesota for his generous gift of transgenic mice. We would also like to thank the following Skidmore College alum for their work performing the preceding experiments: Monica Villegas, Porter Hall, Mitchell Spring, Nicholas Toker, Jenny Zhang, Chloe Larson and Cheyanne Slocum. Furthermore, we would like to thank Skidmore College for funding the development of these methods.

<ol>
	<li>Stucki, D. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mitochondrial+impairments+contribute+to+Spinocerebellar+ataxia+type+1+progression+and+can+be+ameliorated+by+the+mitochondria-targeted+antioxidant+MitoQ.">Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ.</a> Free Radic Biol Med. 97, 427-440 (2016).</li><li>Breuer, M. E., Willems, P. H., Russel, F. G., Koopman, W. J., Smeitink, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modeling+mitochondrial+dysfunctions+in+the+brain,+from+mice+to+men.">Modeling mitochondrial dysfunctions in the brain, from mice to men.</a> J Inherit Metab Dis. 35 (2), 193-210 (2012).</li><li>Breuer, M. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+mitochondrial+OXPHOS+dysfunction+in+the+development+of+neurologic+diseases.">The role of mitochondrial OXPHOS dysfunction in the development of neurologic diseases.</a> Neurobiol Dis. , (2012).</li><li>Hroudov&#225;, J., Singh, N., Fizar, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mitochondrial+dysfunctions+in+neurodegenerative+diseases,+relevance+to+Alzheimer's+disease.">Mitochondrial dysfunctions in neurodegenerative diseases, relevance to Alzheimer's disease.</a> Biomed Res Int. 2014, 175062 (2014).</li><li>Burright, E. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=SCA1+transgenic+mice,+a+model+for+neurodegeneration+caused+by+an+expanded+CAG+trinucleotide+repeat.">SCA1 transgenic mice, a model for neurodegeneration caused by an expanded CAG trinucleotide repeat.</a> Cell. 82 (6), 937-948 (1995).</li><li>Clark, H. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Purkinje+cell+expression+of+a+mutant+allele+of+SCA1+in+transgenic+mice+leads+to+disparate+effects+on+motor+behaviors,+followed+by+a+progressive+cerebellar+dysfunction+and+histological+alterations.">Purkinje cell expression of a mutant allele of SCA1 in transgenic mice leads to disparate effects on motor behaviors, followed by a progressive cerebellar dysfunction and histological alterations.</a> J Neurosci. 17 (19), 7385-7395 (1997).</li><li>Kuznetsov, A. V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Analysis+of+mitochondrial+function+in+situ+in+permeabilized+muscle+fibers,+tissues+and+cells.">Analysis of mitochondrial function in situ in permeabilized muscle fibers, tissues and cells.</a> Nat Protoc. 3 (6), 965-976 (2008).</li><li>Deng-Bryant, Y., Singh, I. N., Carrico, K. M., Hall, E. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroprotective+effects+of+tempol,+a+catalytic+scavenger+of+peroxynitrite-derived+free+radicals,+in+a+mouse+traumatic+brain+injury+model.">Neuroprotective effects of tempol, a catalytic scavenger of peroxynitrite-derived free radicals, in a mouse traumatic brain injury model.</a> J Cereb Blood Flow Metab. 28 (6), 1114-1126 (2008).</li><li>Vaishnav, R. A., Singh, I. N., Miller, D. M., Hall, E. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lipid+peroxidation-derived+reactive+aldehydes+directly+and+differentially+impair+spinal+cord+and+brain+mitochondrial+function.">Lipid peroxidation-derived reactive aldehydes directly and differentially impair spinal cord and brain mitochondrial function.</a> J Neurotrauma. 27 (7), 1311-1320 (2010).</li><li>Matthews, R. T., Yang, L., Browne, S., Baik, M., Beal, M. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coenzyme+Q10+administration+increases+brain+mitochondrial+concentrations+and+exerts+neuroprotective+effects.">Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects.</a> Proc Natl Acad Sci U S A. 95 (15), 8892-8897 (1998).</li><li>Ferrante, R. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroprotective+effects+of+creatine+in+a+transgenic+mouse+model+of+Huntington's+disease.">Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease.</a> J Neurosci. 20 (12), 4389-4397 (2000).</li><li>Ferrante, R. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Therapeutic+effects+of+coenzyme+Q10+and+remacemide+in+transgenic+mouse+models+of+Huntington's+disease.">Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease.</a> J Neurosci. 22 (5), 1592-1599 (2002).</li><li>Hersch, S. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Creatine+in+Huntington+disease+is+safe,+tolerable,+bioavailable+in+brain+and+reduces+serum+8OH2'dG.">Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2'dG.</a> Neurology. 66 (2), 250-252 (2006).</li><li>Yang, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combination+therapy+with+coenzyme+Q10+and+creatine+produces+additive+neuroprotective+effects+in+models+of+Parkinson's+and+Huntington's+diseases.">Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseases.</a> J Neurochem. 109 (5), 1427-1439 (2009).</li><li>Yang, X., Dai, G., Li, G., Yang, E. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coenzyme+Q10+reduces+beta-amyloid+plaque+in+an+APP/PS1+transgenic+mouse+model+of+Alzheimer's+disease.">Coenzyme Q10 reduces beta-amyloid plaque in an APP/PS1 transgenic mouse model of Alzheimer's disease.</a> J Mol Neurosci. 41 (1), 110-113 (2010).</li><li>Sandhir, R., Mehrotra, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quercetin+supplementation+is+effective+in+improving+mitochondrial+dysfunctions+induced+by+3-nitropropionic+acid,+implications+in+Huntington's+disease.">Quercetin supplementation is effective in improving mitochondrial dysfunctions induced by 3-nitropropionic acid, implications in Huntington's disease.</a> Biochim Biophys Acta. 1832 (3), 421-430 (2013).</li><li>Ergonul, P. G., Nergiz, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determination+of+organic+acids+in+olive+fruit+by+HPLC.">Determination of organic acids in olive fruit by HPLC.</a> 'Czech Food Sci. 28 (3), 202-205 (2010).</li><li>Jones, B. J., Roberts, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+quantiative+measurement+of+motor+inco-ordination+in+naive+mice+using+an+acelerating+rotarod.">The quantiative measurement of motor inco-ordination in naive mice using an acelerating rotarod.</a> J Pharm Pharmacol. 20 (4), 302-304 (1968).</li><li>Luong, T. N., Carlisle, H. J., Southwell, A., Patterson, P. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+motor+balance+and+coordination+in+mice+using+the+balance+beam.">Assessment of motor balance and coordination in mice using the balance beam.</a> J Vis Exp. (49), (2011).</li><li>Servadio, A., Koshy, B., Armstrong, D., Antalffy, B., Orr, H. T., Zoghbi, H. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expression+analysis+of+the+ataxin-1+protein+in+tissues+from+normal+and+spinocerebellar+ataxia+type+1+individuals.">Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals.</a> Nat Genet. 10 (1), 94-98 (1995).</li><li>Klement, I. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ataxin-1+nuclear+localization+and+aggregation,+role+in+polyglutamine-induced+disease+in+SCA1+transgenic+mice.">Ataxin-1 nuclear localization and aggregation, role in polyglutamine-induced disease in SCA1 transgenic mice.</a> Cell. 95 (1), 41-53 (1998).</li><li>Serra, H. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gene+profiling+links+SCA1+pathophysiology+to+glutamate+signaling+in+Purkinje+cells+of+transgenic+mice.">Gene profiling links SCA1 pathophysiology to glutamate signaling in Purkinje cells of transgenic mice.</a> Hum Mol Genet. 13 (20), 2535-2543 (2004).</li><li>Carter, R. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+progressive+motor+deficits+in+mice+transgenic+for+the+human+Huntington's+disease+mutation.">Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation.</a> J Neurosci. 19 (8), 3248-3257 (1999).</li><li>Anjomani Virmouni, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+GAA-repeat-expansion-based+mouse+model+of+Friedreich's+ataxia.">A novel GAA-repeat-expansion-based mouse model of Friedreich's ataxia.</a> Dis Model Mech. 8 (3), 225-235 (2015).</li></ol>

저자는 공개 아무것도 없어.

설명 된 바와 같이 이러한 방법을 사용하는 경우, 이들은 검출 및 소뇌 신경 퇴행성 질환의 마우스 모델에서 산화 적 인산화 매개 미토콘드리아 기능 부전을 경감 할 수있다. 결합 된 생화학 적 및 행동 분석은 소뇌 신경 퇴행성 질환의 병리에 미토콘드리아 기여의 정도를 결정하기위한 다각적 인 방법입니다. 신진 대사를 자극하고 미토콘드리아 기능을 강화하기 위해 숙신산과 쥐를 치료함으로?...

미토콘드리아의 전자 전달계를 이용하여 산화 적 인산화 (OXPHOS)를 통해 생성 된 미토콘드리아 ATP의 대부분과, 아데노신 삼인산 (ATP), 세포 에너지의 필수 조효소의 주요 생산자이다. 뇌는 높은 신진 대사 요구와 신경 활동에 전력을 공급하기위한 산화 적 인산화에 대한 의존도를 부여, 미토콘드리아 기능 장애에 매우 민감하다. 그 결과, 미토콘드리아 장애는 노화 과정 트리거 (1) 및 다수의 신경 퇴행성 질환은 2, 3, 4의 병인에 연루되어있다. 따라서 미토콘드리아는 신경 퇴행에 대한 매력적인 치료 대상이되는 것을 다음과 같습니다. 이 프로토콜에서, 우리는 미토콘드리아의 연구를위한 모델 신경 퇴행성 질환과 같은 척수 소 뇌성 실조증 유형 1 (SCA1)의 사용을 채택리터 부전과 미토콘드리아 - 표적으로 한 치료의 개발. SCA1 다른 뇌 영역의 조롱박 소뇌의 뉴런과 뉴런의 진보적 인 변성을 트리거 ataxin-1 유전자 산물의 폴리 글루타민 (polyQ) 반복 확장 돌연변이에 의해 발생합니다. 조롱박 세포 특이 적 프로모터의 제어하에 polyQ 돌연변이 ataxin-1 유전자를 발현합니다 (SCA1 마우스로 지정) 여기서 사용 된 트랜스 제닉 마우스 선은 SCA1 5 조롱박 세포 성분의 표적 분석을 허용한다. SCA1 마우스는 점진적 조롱박 세포의 퇴화를 받아야하고 운동 실조증 보행 (6)을 개발한다. 미토콘드리아 복잡한 기능 장애 및 미토콘드리아 타겟 치료 효능은 분자 및 행동 분석의 배터리로 평가 될 수있다. 복잡한 미토콘드리아 장애는 소뇌 조직 안에서 변화된 산소 소비량을 검출 호흡 분석하여 생체 측정전자 전달계 기판 및 억제제 (7)의 존재. 호흡 분석은 이전에 투과성이 조직, 미토콘드리아 분리하고, 전체 조직 7, 8, 9로 사용되어왔다. 이들은 예컨대 투과 전자 현미경 또는 면역 형광 염색법과 같은 형태 학적 데이터 수집 방법과 달리 미토콘드리아 기능의 직접적인 평가를 허용한다. 전체 조직보다는 격리 미토콘드리아의 사용은 분리 과정 중에 발생할 수 7 건강한 미토콘드리아 바이어스 선택을 방지한다. 도시 된 바와 같이 프로토콜에 적응되면, 호흡 분석은 소뇌 신경 퇴행성 질환 상태에서 미토콘드리아 기능 장애를 검출하기위한 유용한 방법이다. 대사 비특이적 활성제 퇴행성 diseas의 형질 전환 마우스 모델에서 미토콘드리아 기능 부전을 추론하는데 사용될 수있다전자 및 새로운 치료법의 개발에 도움. 퀘르세틴 보효소 Q10과 크레아틴 모든 환자 및 신경 퇴행성 질환 10, 11, 12, 13, 14, 15, 16의 동물 모델에서 신경 퇴행성 질환의 병리를 개선하는 것으로 나타났다. 여기에서 우리는 신진 대사를 자극하고 신경 퇴행성 질환에서 미토콘드리아의 기능을 높일 수있는 새로운 신진 대사 활성화, 숙신산을 제시한다. 활성제가 혈액 뇌 장벽을 가로 지르는 것을 보장하기 위해, HPLC 처리 된 마우스는 17 신경 조직에 배달을 검출하도록 사용 하였다. 숙신산과 같은 대사 표적 수용성 화합물의 치료 효과를 평가하기 위해, 행동 패러다임과 immunopathological 연구 전지가 사용될 수있다. 뒤소뇌 신경 퇴행성 질환, 풋 프린트 활주로 분석, 빔 분석 및 가속 회전로드 분석에서 발견 된 모터 조정 적자에 전자는 행동 병리학 6, 18, 19의 구조를 검색하는 데 사용됩니다. 이러한 조치는 소뇌 조직 6, 20, 21의 정의 소엽 내에서 분자 (조롱박 세포 돌기의 아버 길이로 정의) 층의 두께 및 조롱박 세포 소마 수를 평가하여 소뇌 cytoarchitecture의 immunopathological 평가로 보충된다. 여기에서 우리는 대사 대상으로 수용성 화합물 검출 및 미토콘드리아 기능 장애의 치료를위한 여러 신경 병리학 및 행동 방법을 제시한다. 우리는 SCA1의 트란에 미토콘드리아 기능 장애를 분석하는 미토콘드리아 호흡의 생체 분석을 사용sgenic 마우스입니다. 더욱이, 우리는 질병 증상과 병리 더 SCA1 질병 진행에서 미토콘드리아 기능 부전을 연루 수용성 미토콘드리아 부스터 숙신산 향상되어 있음을 보여준다.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Adenosine diphosphate</td>
			<td>Sigma Aldrich</td>
			<td>A2754</td>
			<td>ADP</td>
		</tr>
		<tr>
			<td>Ascorbate</td>
			<td>Sigma Aldrich</td>
			<td>A7631</td>
			<td></td>
		</tr>
		<tr>
			<td>Bovine serum albumin</td>
			<td>Sigma Aldrich</td>
			<td>A2153</td>
			<td>BSA</td>
		</tr>
		<tr>
			<td>4&#39;,6-Diamidino-2-phenylindole</td>
			<td>Sigma Aldrich</td>
			<td>D9542</td>
			<td>DAPI</td>
		</tr>
		<tr>
			<td>Digitonin</td>
			<td>Sigma Aldrich</td>
			<td>D141</td>
			<td></td>
		</tr>
		<tr>
			<td>Dithiothreitol</td>
			<td>Sigma Aldrich</td>
			<td>D0632</td>
			<td>DTT</td>
		</tr>
		<tr>
			<td>Donkey serum</td>
			<td>Sigma Aldrich</td>
			<td>D9663</td>
			<td></td>
		</tr>
		<tr>
			<td>Glutamate</td>
			<td>Sigma Aldrich</td>
			<td>1446600</td>
			<td></td>
		</tr>
		<tr>
			<td>Malate</td>
			<td>Sigma Aldrich</td>
			<td>6994</td>
			<td></td>
		</tr>
		<tr>
			<td>Mannitol</td>
			<td>Sigma Aldrich</td>
			<td>M4125</td>
			<td></td>
		</tr>
		<tr>
			<td>Paraformaldehyde</td>
			<td>Sigma Aldrich</td>
			<td>P6148</td>
			<td></td>
		</tr>
		<tr>
			<td>Potassium-lactobionate</td>
			<td>Bio-Sugars</td>
			<td>69313-67-3</td>
			<td></td>
		</tr>
		<tr>
			<td>Rotenone</td>
			<td>Sigma Aldrich</td>
			<td>R8875</td>
			<td></td>
		</tr>
		<tr>
			<td>Saponin</td>
			<td>Sigma Aldrich</td>
			<td>47036</td>
			<td></td>
		</tr>
		<tr>
			<td>Succinic Acid</td>
			<td>Sigma Aldrich</td>
			<td>S3674</td>
			<td></td>
		</tr>
		<tr>
			<td>N,N,N&#8242;,N&#8242;-Tetramethyl-p-phenylenediamine</td>
			<td>Sigma Aldrich</td>
			<td>T7394</td>
			<td>TMPD</td>
		</tr>
		<tr>
			<td>Triton X-100</td>
			<td>Sigma Aldrich</td>
			<td>T9284</td>
			<td></td>
		</tr>
		<tr>
			<td>Urea</td>
			<td>Sigma Aldrich</td>
			<td>U0631</td>
			<td></td>
		</tr>
		<tr>
			<td>Vectashield mounting medium</td>
			<td>Vector Labs</td>
			<td>H-1000</td>
			<td></td>
		</tr>
		<tr>
			<td>Antibodies</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>11NQ antibody (anti-ataxin-1 )</td>
			<td></td>
			<td></td>
			<td>Servadio, et al. 1995, PMID: 7647801</td>
		</tr>
		<tr>
			<td>Alexa Fluor 488 anti-mouse secondary antibody</td>
			<td>Life Technologies</td>
			<td>A-11015</td>
			<td></td>
		</tr>
		<tr>
			<td>Alexa Fluor 594 anti-rabbit secondary antibody</td>
			<td>Life Technologies</td>
			<td>A-11012</td>
			<td></td>
		</tr>
		<tr>
			<td>Calbindin antibody (goat)</td>
			<td>Santa Cruz</td>
			<td>C-20</td>
			<td></td>
		</tr>
		<tr>
			<td>Animals</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Control transgenic mice</td>
			<td>Harry Orr, Ph.D.</td>
			<td>A02</td>
			<td>Burright, et al. 1997, PMID: 9217978</td>
		</tr>
		<tr>
			<td>SCA1 mice</td>
			<td>Harry Orr, Ph.D.</td>
			<td>B05</td>
			<td>Burright, et al. 1997, PMID: 9217978</td>
		</tr>
		<tr>
			<td>Wildtype mice</td>
			<td>The Jackson Laboratory</td>
			<td>001800</td>
			<td></td>
		</tr>
		<tr>
			<td>Equipment</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>ESM-100L microtome</td>
			<td>ERMA</td>
			<td></td>
			<td>Sledge microtome</td>
		</tr>
		<tr>
			<td>Fluoview FV1200 Confocal Microscope</td>
			<td>Olympus</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Glycerol-gelatin slides</td>
			<td>FD Neuro Technologies</td>
			<td>PO101</td>
			<td></td>
		</tr>
		<tr>
			<td>Hamilton syringe</td>
			<td>Sigma Aldrich</td>
			<td>VCAT 80465</td>
			<td></td>
		</tr>
		<tr>
			<td>OXYT1 Oxytherm Electrode Control Unit</td>
			<td>Hansatech Instruments</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>P.T.F.E. paper</td>
			<td>Cole-Parmer</td>
			<td>UX-08277-15</td>
			<td></td>
		</tr>
		<tr>
			<td>Rotallion Rotarod</td>
			<td>PPP&#38;G</td>
			<td></td>
			<td>contact corresponding author for information</td>
		</tr>
		<tr>
			<td>Ultimate 3000 HPLC</td>
			<td>Dionex</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Software</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>ImageJ</td>
			<td>National Institute of Health</td>
			<td></td>
			<td><a href="http://imagej.nih.gov/ij/">http://imagej.nih.gov/ij/</a></td>
		</tr>
		<tr>
			<td>Cell counter plugin (for ImageJ)</td>
			<td>National Institute of Health</td>
			<td></td>
			<td><a href="http://rsb.info.nih.gov/ij/plugins/cell-counter.html">http://rsb.info.nih.gov/ij/plugins/cell-counter.html</a></td>
		</tr>
		<tr>
			<td>3P&#38;G Rota-Rod v3.3.3 (rotarod software)</td>
			<td>PPP&#38;G</td>
			<td></td>
			<td>contact corresponding author for information</td>
		</tr>
		<tr>
			<td>Phidget21.dll (required for rotarod software)</td>
			<td>DLL-Files.com</td>
			<td></td>
			<td><a href="https://www.dll-files.com/phidget21.dll.html">https://www.dll-files.com/phidget21.dll.html</a></td>
		</tr>
	</tbody>
</table>

treating sca1 mice with water-soluble compounds to non-specifically boost mitochondrial function

미토콘드리아 기능 장애는 노화 과정에서 여러 유전 척수 소 뇌성 운동 실조증과 소뇌의 진보적 인 변성에 의해 표시 다른 운동 장애를 포함한 신경 퇴행성 질환에 중요한 역할을한다. 이 프로토콜의 목적은 척수 소 뇌성 실조증 유형 1 (SCA1)에서 미토콘드리아 기능 부전을 평가하고, 병의 진행을 느리게하는 수용성 화합물 숙신산 통해 호흡 대사 약물 표적의 효능을 평가하는 것이다. 이 접근은 다른 소뇌 질환에 적용 할 수있다 수용성 요법 숙주에 적응 될 수있다. 미토콘드리아 호흡의 생체 분석을 감지하고 미토콘드리아 기능에서 질병 관련 변경 사항을 정량화하는 데 사용됩니다. 유전 적 증거 (게시되지 않은 데이터)와 SCA1 마우스 모델에서 미토콘드리아 기능 장애의 단백체 증거, 우리는 수용성 대사 부스터의 치료의 효능을 평가홈 케이지 마시는 물에 직접 화합물을 용해하여 uccinic 산. 혈액 뇌 장벽을 통과하는 약물의 능력은 고성능 액체 크로마토 그래피 (HPLC)를 사용하여 추론 될 수있다. 이들 화합물의 효능은 다음 가속 로타로드 (rotarod), 밸런스 빔 테스트 및 공간 분석 등 다양한 행동 패러다임을 사용하여 테스트 할 수있다. 소뇌 Cytoarchitectural 무결성 조롱박 세포핵 및 조롱박 수지상 세포 및 소마 검출 면역 분석법을 이용하여 평가할 수있다. 이러한 방법은 미토콘드리아 장애와 소뇌 신경 퇴행성 질환의 수용성 화합물 치료의 효능을 결정하기위한 견고한 기술이다.

숙신산과 소뇌 미토콘드리아의 약물 학적 타겟팅을 통해 우리는 소뇌 신경 퇴행성 질환 SCA1의 마우스 모델에서 미토콘드리아 기능 장애를 방지 할 수 있습니다. 숙신산 탈수소 효소, 숙신산,의 표준 전자 공여체 치료 (그림 1A) 다음과 같은 치료 및 신경 병리학 적 평가의 두 번째 주 동안 행동 평가의 시작과 함께, 한 달 동안 SCA1 마우스의 홈 케이?...

Watch this Scientific Journal Video about Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function at JoVE.com

Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function

We present a biochemical and behavioral protocol to evaluate the efficacy of mitochondria-targeted water-soluble compounds for the treatment of Spinocerebellar ataxia type 1 (SCA1) and other cerebellar neurodegenerative diseases.

에 수용성 화합물로 SCA1 마우스 치료가 아닌 것은 - 특히 미토콘드리아 기능 향상

Mitochondrial dysfunction plays a significant role in the aging process and in neurodegenerative diseases including several hereditary spinocerebellar ...

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10.5K 조회수.  Skidmore College. We present a biochemical and behavioral protocol to evaluate the efficacy of mitochondria-targeted water-soluble compounds for the treatment of Spinocerebellar ataxia type 1 (SCA1) and other cerebellar neurodegenerative diseases. 

비디오: Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function

Assessing Endothelial Vasodilator Function with the Endo-PAT 2000

The endothelium is a delicate monolayer of cells that lines all blood vessels, and which comprises the systemic and lymphatic capillaries. By virtue of the panoply of paracrine factors that it secretes, the endothelium regulates the contractile and proliferative state of the underlying vascular smooth muscle, as well as the interaction of the vessel wall with circulating blood elements. Because of its central role in mediating vessel tone and growth, its position as gateway to circulating immune cells, and its local regulation of hemostasis and coagulation, the the properly functioning endothelium is the key to cardiovascular health. Conversely, the earliest disorder in most vascular diseases is endothelial dysfunction.
In the arterial circulation, the healthy endothelium generally exerts a vasodilator influence on the vascular smooth muscle. There are a number of methods to assess endothelial vasodilator function. The Endo-PAT 2000 is a new device that is used to assess endothelial vasodilator function in a rapid and non-invasive fashion. Unlike the commonly used technique of duplex ultra-sonography to assess flow-mediated vasodilation, it is totally non-operator-dependent, and the equipment is an order of magnitude less expensive. The device records endothelium-mediated changes in the digital pulse waveform known as the PAT ( peripheral Arterial Tone) signal, measured with a pair of novel modified plethysmographic probes situated on the finger index of each hand. Endothelium-mediated changes in the PAT signal are elicited by creating a downstream hyperemic response. Hyperemia is induced by occluding blood flow through the brachial artery for 5 minutes using an inflatable cuff on one hand. The response to reactive hyperemia is calculated automatically by the system. A PAT ratio is created using the post and pre occlusion values. These values are normalized to measurements from the contra-lateral arm, which serves as control for non-endothelial dependent systemic effects. Most notably, this normalization controls for fluctuations in sympathetic nerve outflow that may induce changes in peripheral arterial tone that are superimposed on the hyperemic response.
In this video we demonstrate how to use the Endo-PAT 2000 to perform a clinically relevant assessment of endothelial vasodilator function.

A noninvasive procedure to assess endothelial function is demonstrated using the Endo-PAT 2000.

엔도 - PAT 2000 내피 Vasodilator 기능을 평가

The endothelium is a delicate monolayer of cells that lines all blood vessels, and which comprises the systemic and lymphatic capillaries. By virtue of ...

연구

의학

Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma

A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA approved in April 2011 for the treatment of patients 22 years or older with rGBM. The device delivers alternating electric fields and is programmed to ensure maximal tumor cell kill1.
Glioblastoma is the most common type of glioma and has an estimated incidence of approximately 10,000 new cases per year in the United States alone2. This tumor is particularly resistant to treatment and is uniformly fatal especially in the recurrent setting3-5. Prior to the approval of the TTF System, the only FDA approved treatment for rGBM was bevacizumab6. Bevacizumab is a humanized monoclonal antibody targeted against the vascular endothelial growth factor (VEGF) protein that drives tumor angiogenesis7. By blocking the VEGF pathway, bevacizumab can result in a significant radiographic response (pseudoresponse), improve progression free survival and reduce corticosteroid requirements in rGBM patients8,9. Bevacizumab however failed to prolong overall survival in a recent phase III trial26. A pivotal phase III trial (EF-11) demonstrated comparable overall survival between physicians&#8217; choice chemotherapy and TTF Therapy but better quality of life were observed in the TTF arm10.
There is currently an unmet need to develop novel approaches designed to prolong overall survival and/or improve quality of life in this unfortunate patient population. One appealing approach would be to combine the two currently approved treatment modalities namely bevacizumab and TTF Therapy. These two treatments are currently approved as monotherapy11,12, but their combination has never been evaluated in a clinical trial. We have developed an approach for combining those two treatment modalities and treated 2 rGBM patients. Here we describe a detailed methodology outlining this novel treatment protocol and present representative data from one of the treated patients.

A novel methodology that is employed for the treatment of recurrent glioblastomas is described. This treatment approach employs the application of alternating electric tumor treating fields (TTFields), known as TTF Therapy in combination with bevacizumab, a targeted agent that is currently FDA approved as monotherapy.

재발 성 아교 모세포종의 치료를 위해 베바 시주 맙과 조합하여 필드 요법 치료 종양

A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA ...

Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology.

This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

깊은 뇌 자극과 Saccadometry를 사용하여 정상 및 병적 뇌 기능을 연구하는

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including ...

Assessment of Respiratory Function in Conscious Mice by Double-chamber Plethysmography

Air volume changes created by a conscious subject breathing spontaneously within a body box are at the basis of plethysmography, a technique used to non-invasively assess some features of the respiratory function in humans as well as in laboratory animals. The present article focuses on the application of the double-chamber plethysmography (DCP) in small animals. It provides background information on the methodology as well as a detailed step-by-step procedure to successfully assess respiratory function in conscious, spontaneously breathing animals in a non-invasive manner. The DCP can be used to monitor the respiratory function of multiple animals in parallel, as well as to identify changes induced by aerosolized substances over a chosen time period and in a repeated manner. Experiments on control and allergic mice are used herein to demonstrate the utility of the technique, explain the associated outcome parameters, as well as to discuss the related advantages and shortcomings. Overall, the DCP provides valid and theoretically sound readouts that can be trusted to evaluate the respiratory function of conscious small animals both at baseline and after challenges with aerosolized substances.

The objective of the present article is to provide a detailed description of the recommended procedures to evaluate respiratory function in conscious mice by double-chamber plethysmography.

더블 챔버 Plethysmography 여 의식 생쥐에 호흡기 기능의 평가

Air volume changes created by a conscious subject breathing spontaneously within a body box are at the basis of plethysmography, a technique used to ...

Non-invasive Assessment of Dorsiflexor Muscle Function in Mice

Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively affect skeletal muscle. This can result in a loss of muscle mass (atrophy) and/or loss of muscle quality (reduced force per unit of muscle mass), both of which are prevalent in chronic disease, muscle-specific disease, immobilization, and aging (sarcopenia). Skeletal muscle function in animals can be evaluated by a range of different tests. All tests have limitations related to the physiological testing environment, and the selection of a specific test often depends on the nature of the experiments. Here, we describe an in vivo, non-invasive technique involving a helpful and easy assessment of force frequency-curve (FFC) in mice that can be performed on the same animal over time. This permits monitoring of disease progression and/or efficacy&#160;of a potential therapeutic treatment.

Measurement of rodent skeletal muscle contractile function is a useful tool that can be used to track disease progression as well as efficacy of therapeutic intervention. We describe here the non-invasive, in vivo assessment of the dorsiflexor muscles that can be repeated over time in the same mouse.

비-침략 적 쥐에서 Dorsiflexor 근육 기능 평가

Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively ...

A Non-Invasive Method for Generating the Cyclic Loading-Induced Intra-Articular Cartilage Lesion Model of the Rat Knee

The pathophysiology of primary osteoarthritis (OA) remains unclear. However, a specific subclassification of OA in relatively younger age groups is likely correlated with a history of articular cartilage damage and ligament avulsion. Surgical animal models of OA of the knee play an important role in understanding the onset and progression of post-traumatic OA and aid in the development of novel therapies for this disease. However, non-surgical models have been recently considered to avoid traumatic inflammation that could affect the evaluation of the intervention. 
In this study, an intra-articular cartilage lesion rat model induced by in vivo cyclic compressive loading was developed, which allowed researchers to (1) determine the optimal magnitude, speed, and duration of load that could cause focal cartilage damage; (2) assess post-traumatic spatiotemporal pathological changes in chondrocyte vitality; and (3) evaluate the histological expression of destructive or protective molecules that are involved in the adaptation and repair mechanisms against joint compressive loads. This report describes the experimental protocol for this novel cartilage lesion in a rat model.

Here, we present the cyclic loading-induced intra-articular cartilage lesion model of the rat knee, generated by 60 cyclic compressions over 20 N, resulting in damage to the femoral condylar cartilage in rats.

래트 무릎의 순환 로딩 유도 관절내 연골 병변 모델을 생성하기 위한 비침습적 방법

The pathophysiology of primary osteoarthritis (OA) remains unclear. However, a specific subclassification of OA in relatively younger age groups is likely ...

고분해능 호흡 측정법을 통한 인간 정자 세포의 호흡 측정

High-Resolution Respirometry to Assess Mitochondrial Function in Human Spermatozoa

Semen quality is often studied by routine semen analysis, which is descriptive and often inconclusive. Male infertility is associated with altered sperm mitochondrial activity, so the measurement of sperm mitochondrial function is an indicator of sperm quality. High-resolution respirometry is a method of measuring the oxygen consumption of cells or tissues in a closed-chamber system. This technique can be implemented to measure respiration in human sperm and provides information about the quality and integrity of the sperm mitochondria. High-resolution respirometry allows the cells to move freely, which is an a priori advantage in the case of sperm. This technique can be applied with intact or permeabilized spermatozoa and allows for the study of intact sperm mitochondrial function and the activity of individual respiratory chain complexes. The high-resolution oxygraph instrument uses sensors to measure the oxygen concentration coupled with sensitive software to calculate the oxygen consumption. The data are used to calculate respiratory indices based on the oxygen consumption ratios. Consequently, the indices are the proportions of two oxygen consumption rates and are internally normalized to the cell number or protein mass. The respiratory indices are an indicator of sperm mitochondrial function and dysfunction.

저자 스포트라이트: 정자 대사와 미토콘드리아 기능을 밝히는 남성 불임 연구 발전 

The analysis of sperm mitochondrial function by high-resolution respirometry permits the measurement of the oxygen consumption of freely moving spermatozoa in a closed-chamber system. The technique can be applied to measure respiration in human spermatozoa, which provides information on sperm mitochondrial characteristics and integrity.

인간 정자의 미토콘드리아 기능을 평가하기 위한 고분해능 호흡 측정법

Semen quality is often studied by routine semen analysis, which is descriptive and often inconclusive. Male infertility is associated with altered sperm ...

Rat DRG 압축 모델을 위한 표준화된 Tuina 프로토콜

Analgesic Effect of Tuina on Rat Models with Compression of the Dorsal Root Ganglion Pain

Neuropathic pain is a prevalent condition that affects 6.9%-10% of the population and results from nerve damage due to various etiologies, such as lumbar disc herniation, spinal canal stenosis, and intervertebral foramen stenosis. Although Tuina, a traditional Chinese manual therapy, has shown analgesic effects in clinical practice for the treatment of neuropathic pain, its underlying neurobiological mechanisms remain unclear. Animal models are essential for elucidating the basic principles of Tuina. In this study, we propose a standardized Tuina protocol for rats with compression of the dorsal root ganglion (DRG), which involves inducing DRG compression by inserting a stainless steel rod into the intervertebral foramen, performing Tuina manipulation with specific parameters of location, intensity, and frequency in a controlled environment, and assessing the behavioral and histopathological outcomes of Tuina treatment. This article also discusses the potential clinical implications and limitations of the study and suggests directions for future research on Tuina.

저자 스포트라이트: 등뿌리 신경절 통증을 압박하는 쥐 모델에 대한 Tuina의 진통 효과  

This article presents a manipulation for treating chronic compression of the dorsal root ganglion in rats using Tuina therapy, along with a method for evaluating its effectiveness based on pain behavior and histopathological results.

등쪽 뿌리 신경절 통증의 압축이 있는 쥐 모델에 대한 Tuina의 진통 효과

Neuropathic pain is a prevalent condition that affects 6.9%-10% of the population and results from nerve damage due to various etiologies, such as lumbar ...

에 수용성 화합물로 SCA1 마우스 치료가 아닌 것은 - 특히 미토콘드리아 기능 향상

요약

더 많은 비디오 탐색

이 비디오의 챕터

엔도 - PAT 2000 내피 Vasodilator 기능을 평가

재발 성 아교 모세포종의 치료를 위해 베바 시주 맙과 조합하여 필드 요법 치료 종양

깊은 뇌 자극과 Saccadometry를 사용하여 정상 및 병적 뇌 기능을 연구하는

더블 챔버 Plethysmography 여 의식 생쥐에 호흡기 기능의 평가

비-침략 적 쥐에서 Dorsiflexor 근육 기능 평가

래트 무릎의 순환 로딩 유도 관절내 연골 병변 모델을 생성하기 위한 비침습적 방법

인간 정자의 미토콘드리아 기능을 평가하기 위한 고분해능 호흡 측정법

인간 정자의 미토콘드리아 기능을 평가하기 위한 고분해능 호흡 측정법

인간 정자의 미토콘드리아 기능을 평가하기 위한 고분해능 호흡 측정법

등쪽 뿌리 신경절 통증의 압축이 있는 쥐 모델에 대한 Tuina의 진통 효과