目的探讨帕金森病(PD)患者皮肤小神经纤维的病理特点。方法收集16例临床确诊并符合纳入和排除标准的PD患者和性别年龄匹配的16例健康对照者的临床资料和神经电生理结果,对PD症状及周围神经病变进行评估。所有受试者行小腿皮肤活组织检查...目的探讨帕金森病(PD)患者皮肤小神经纤维的病理特点。方法收集16例临床确诊并符合纳入和排除标准的PD患者和性别年龄匹配的16例健康对照者的临床资料和神经电生理结果,对PD症状及周围神经病变进行评估。所有受试者行小腿皮肤活组织检查,通过标准化泛轴突标记蛋白基因产物9.5(PGP9.5)和生长相关蛋白43(GAP-43)两种免疫组织化学染色定量表皮内神经纤维密度(Intraepidermal nerve fiber density,IENFD),并进行统计学分析。结果16例PD患者,男7例,女9例,年龄(66.000±9.675)岁,Hoehn and Yahr(H-Y)分期(1.906±0.612)。PD组尺神经、正中神经、腓肠神经远端感觉潜伏期较对照组延长(P<0.05),余2组间神经电生理结果未见统计学差异(P>0.05)。PD组PGP9.5和GAP-43染色下IENFD值均低于健康对照组(8.618±3.984根/mm vs18.198±5.387根/mm,4.543±3.363根/mm vs 14.174±5.485根/mm;P<0.05)。两种染色下IENFD值与PD的临床症状有相关性。GAP-43/PGP9.5染色下IENFD比值在2组之间无统计学差异(0.575±0.380 vs 0.787±0.218;P>0.05)。结论PD患者存在周围神经损害,以小神经纤维受累为主,大直径神经纤维受累不明显,皮肤活检是诊断PD小纤维神经病较为可靠的方法。展开更多
Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using re...Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.展开更多
文摘目的探讨帕金森病(PD)患者皮肤小神经纤维的病理特点。方法收集16例临床确诊并符合纳入和排除标准的PD患者和性别年龄匹配的16例健康对照者的临床资料和神经电生理结果,对PD症状及周围神经病变进行评估。所有受试者行小腿皮肤活组织检查,通过标准化泛轴突标记蛋白基因产物9.5(PGP9.5)和生长相关蛋白43(GAP-43)两种免疫组织化学染色定量表皮内神经纤维密度(Intraepidermal nerve fiber density,IENFD),并进行统计学分析。结果16例PD患者,男7例,女9例,年龄(66.000±9.675)岁,Hoehn and Yahr(H-Y)分期(1.906±0.612)。PD组尺神经、正中神经、腓肠神经远端感觉潜伏期较对照组延长(P<0.05),余2组间神经电生理结果未见统计学差异(P>0.05)。PD组PGP9.5和GAP-43染色下IENFD值均低于健康对照组(8.618±3.984根/mm vs18.198±5.387根/mm,4.543±3.363根/mm vs 14.174±5.485根/mm;P<0.05)。两种染色下IENFD值与PD的临床症状有相关性。GAP-43/PGP9.5染色下IENFD比值在2组之间无统计学差异(0.575±0.380 vs 0.787±0.218;P>0.05)。结论PD患者存在周围神经损害,以小神经纤维受累为主,大直径神经纤维受累不明显,皮肤活检是诊断PD小纤维神经病较为可靠的方法。
基金supported by the Spanish Ministry of Economy and Competitiveness(PID2019-106498GB-I0)Instituto de Salud Carlos III,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”(PI19/00071)+2 种基金Fundación Séneca,Agencia de Ciencia y Tecnología Región de Murcia(19881/GERM/15)Spanish Ministry of Science and Innovation(PID 2019-106498 GB-I00)Intramural Research Program of the National Eye Institute,National Institutes of Health(NIH/NEI RO1 EY029087)。
文摘Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.
