Trimethyltin (TMT) destroys specific subfields of the hippocampus in the rat. TMT also increases choline acetyltransferase (ChAT) activity in CA1 of Ammon's horn and the outer molecular layer of the dentate gyrus. This observation suggests that axonal sprouting occurs in the cholinergic septohippocampal system in response to TMT. However, neither does-response nor time course data are available for the effects of TMT on this enzyme. The effects of three dose levels of TMT on ChAT activity in CA1 and the dentate gyrus were determined in Experiment 1 and ChAT activity in these two areas was measured at six time points following exposure to TMT in Experiment 2. Only the highest dose of TMT (6 mg/kg) significantly increased ChAT activity. ChAT activity in the dentate gyrus increased significantly by 3 d after administration and continued to increase until 21 d after exposure. A significant increase was not observed in CA1 until 7 d after exposure to TMT. Asymptotic levels were still reached at d 21. These results indicate a steep dose-response curve for TMT-induced changes in ChAT activity in the hippocampal formation and that this marker of cholinergic activity is more sensitive to perturbation by TMT in the dentate gyrus than Ammon's horn.

No description available.

Final publication is available at http://dx.doi.org/10.1111/ejn.12882 / 京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13040号 / 論医博第2115号 / 新制||医||1017(附属図書館) / 33032 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 影山 龍一郎, 教授 髙橋 良輔 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

No description available.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24797号 / 医博第4989号 / 新制||医||1066(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 花川 隆, 教授 髙橋 良輔, 教授 高橋 淳 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24512号 / 医博第4954号 / 新制||医||1064(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 花川 隆, 教授 古川 壽亮, 教授 中本 裕士 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

In an average year more than 1.7 million people will experience a traumatic brain injury (TBI) in the United States. It is known that atrophy occurs across a spectrum for TBI patients, ranging from mild to severe. Current conventional magnetic resonance imaging (MRI) methods are inconsistent in detecting this atrophy on the milder end of the spectrum. Also more contemporary imaging tools, although efficient, are too time consuming for clinical applicability. It is for these reasons that a quick and efficient measurement for detecting this atrophy is needed by clinicians. The measuring of third ventricle width had the potential to be this measurement, since it is known that ventricular dilation is an indirect measure of brain atrophy. This study used two different data sets acquired at multiple sites. A total of 152 TBI patients' MRI scans were analyzed with diagnosis ranging from mild to severe. They have been age matched with 97 orthopedic injury controls. All scans were analyzed using Freesurfer® auto-segmentation software to acquire cortical, subcortical, and ventricular volumes. These metrics were then used as a standard of efficacy which we tested the new third ventricle width protocol against. There was no statistically significant difference between the overall TBI group and OI group (Welch's F(1,238.435) = 1.091, p= .267). The complicated mild injury subgroup was significantly increased from the mild subgroup (p= .001, d= .87). The grand average third ventricle width measurement was the best prognosticator of all measures analyzed despite only predicting 35.1% of cases correctly. The findings suggest that the third ventricle width measurement is insensitive to atrophy between all groups as hypothesized.

Karpaltunnelsyndrom är den vanligaste formen av nervkompression. Vid förträngning av kanalen kan nervus medianus komprimeras vilket ger symptom i handen som domningar, känselbortfall, smärtor och atrofier pga. demyelinisering och axonal förlust i nerven. En vanlig behandlingsform är kirurgisk dekompression. Elektrofysiologisk mätning (neurografi) används för att bekräfta diagnosen karpaltunnelsyndrom och för att gradera svårighetsgraden av nervskadan. Syftet med studien är att med neurografi över karpaltunneln, följa läkningsförloppet av nervus medianus efter karpaltunneloperation och att utvärdera den kliniska användbarheten av en neurografisk metod, 7-14 metoden. Vid uppföljning två månader efter karpaltunneloperation har patienternas neurografiresultat, latenser, hastigheter och amplituder, förbättrats signifikant på gruppnivå. På individnivå visar resultaten att de patienter som hade en kraftig påverkan av n medianus pre-operativt förbättrades i högre grad i förhållande till dem som hade en lindrigare påverkan. Flera fördelar ses med 7-14 metoden vilket gör den till en kliniskt användbar neurofysiologisk metod som bör användas vid utredning av karpaltunnelsyndrom.

Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by progressive loss of striatal and cortical neurons. HD is caused by an abnormal polyglutamine (polyQ) expansion in Huntingtin protein (HTT). HTT controls vesicular trafficking along axons in neurons through interaction with components of the molecular motor machinery. Arginine methylation is one of the most abundant post-translational modifications (PTMs) and is catalyzed by protein arginine methyltransferases (PRMTs). Recent evidence supports a key role for arginine methylation in neurodegeneration and particularly in polyglutamine diseases. However, whether HTT is methylated at arginine residues has not been investigated yet and the role of arginine methylation in HD pathogenesis remains to be fully elucidated. In this thesis, I show that vesicle-associated HTT is methylated in vivo at two evolutionarily conserved arginine residues, namely R101 and R118. Methylation of HTT at R118 is catalyzed by Protein Arginine Methyltransferase 6 (PRMT6), which localizes on vesicles together with HTT, whereas further analyses are required to identify the enzyme(s) responsible for R101 methylation. Interestingly, loss of PRMT6-mediated R118 methylation reduces the association of HTT with vesicles, impairs anterograde axonal transport and exacerbates polyQ-expanded HTT toxicity. Conversely, PRMT6 overexpression improves the global efficiency of anterograde axonal transport and rescues cell death in neurons expressing polyQ-expanded HTT. These findings establish a crucial role of arginine methylation as a modulator of both normal HTT function and polyQ-expanded HTT toxicity and identify PRMT6 as a novel modifier of HD pathogenesis. Importantly, defects in HTT methylation may contribute to neurodegeneration in HD and promoting arginine methylation of HTT might represent a new therapeutic strategy for HD.