{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:57:10Z","timestamp":1787014630610,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,3,7]],"date-time":"2012-03-07T00:00:00Z","timestamp":1331078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p>\n                    Spinocerebellar ataxia type 6 (SCA6) is an autosomal\u2010dominant neurodegenerative disorder caused by a small expansion of tri\u2010nucleotide (CAG) repeat encoding polyglutamine (polyQ) in the gene for \u03b1\n                    <jats:sub>1A<\/jats:sub>\n                    voltage\u2010dependent calcium channel (Ca\n                    <jats:sub>v<\/jats:sub>\n                    2.1). Thus, this disease is one of the nine neurodegenerative disorders called polyQ diseases. The Purkinje cell predominant neuronal loss is the characteristic neuropathology of SCA6, and a 75\u2010kDa carboxy\u2010terminal fragment (CTF) of Ca\n                    <jats:sub>v<\/jats:sub>\n                    2.1 containing polyQ, which remains soluble in normal brains, becomes insoluble in the cytoplasm of SCA6 Purkinje cells. Because the suppression of the brain\u2010derived neurotrophic factor (BDNF) expression is a potentially momentous phenomenon in many other polyQ diseases, we implemented BDNF expression analysis in SCA6 human cerebellum using quantitative RT\u2010PCR for the\n                    <jats:italic>BDNF<\/jats:italic>\n                    mRNA, and by immunohistochemistry for the BDNF protein. We observed significantly reduced\n                    <jats:italic>BDNF<\/jats:italic>\n                    mRNA levels in SCA6 cerebellum (\n                    <jats:italic>n<\/jats:italic>\n                    \u2003=\u20033) compared to controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2003=\u20036) (Mann\u2013Whitney\n                    <jats:italic>U<\/jats:italic>\n                    \u2010test,\n                    <jats:italic>P<\/jats:italic>\n                    \u2003=\u20030.0201). On immunohistochemistry, BDNF protein was only weakly stained in control cerebellum. On the other hand, we found numerous BDNF\u2010immunoreactive granules in dendrites of SCA6 Purkinje cells. We did not observe similar BDNF\u2010immunoreactive granules in other polyQ diseases, such as Huntington's disease or SCA2. As we often observed that the 1C2\u2010positive Ca\n                    <jats:sub>v<\/jats:sub>\n                    2.1 aggregates existed more proximally than the BDNF\u2010positive granules in the dendrites, we speculated that the BDNF protein trafficking in dendrites may be disturbed by Ca\n                    <jats:sub>v<\/jats:sub>\n                    2.1 aggregates in SCA6 Purkinje cells. We conclude that the SCA6 pathogenic mechanism associates with the\n                    <jats:italic>BDNF<\/jats:italic>\n                    mRNA expression reduction and abnormal localization of BDNF protein.\n                  <\/jats:p>","DOI":"10.1111\/j.1440-1789.2012.01302.x","type":"journal-article","created":{"date-parts":[[2012,3,7]],"date-time":"2012-03-07T02:45:06Z","timestamp":1331088306000},"page":"595-603","source":"Crossref","is-referenced-by-count":32,"title":["Reduced brain\u2010derived neurotrophic factor (BDNF) mRNA expression and presence of BDNF\u2010immunoreactive granules in the spinocerebellar ataxia type 6 (SCA6) cerebellum"],"prefix":"10.1111","volume":"32","author":[{"given":"Makoto","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinya","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomu","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Obayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Niimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Ishiguro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsunori","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Toyoshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Takao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Murayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Eishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehiro","family":"Mizusawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,7]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/514867"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420616"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0197-62"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.7.1185"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.12.1753"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(98)00009-4"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-004-0142-7"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.113042"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.1990"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80943-5"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1080\/08977190410001723308"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02237-X"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2007.01.003"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059581"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05137.x"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.100110097"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1056784"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.14.2197"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0630-0"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10422"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.06.018"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.06.032"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0905-11.2011"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2007.00378.x"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7483"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.67.1.86"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1863-09.2009"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(96)00245-X"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01082-3"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00219-X"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-6-42"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-009-8050-7"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/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