{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:24:06Z","timestamp":1791206646925,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2008,2,8]],"date-time":"2008-02-08T00:00:00Z","timestamp":1202428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The neuronal ceroidlipofuscinoses (NCL) are a group of neurodegenerative disorders and are the most common lysosomal storage diseases of infancy and childhood. Juvenile NCL is caused by <jats:italic>CLN3<\/jats:italic> mutation, producing retinal degeneration, uncontrollable seizures, cognitive and motor decline, and early death before the age of 30 years. To study the pathogenetic mechanisms of the disease, <jats:italic>Cln3<\/jats:italic> knock\u2010in mice (<jats:italic>Cln3<jats:sup>\u0394ex7\/8<\/jats:sup><\/jats:italic>) have been generated, which reproduce the 1.02\u2010kb deletion in the <jats:italic>CLN3<\/jats:italic> gene observed in more than 85% of juvenile NCL patients. To characterize the impact of the common <jats:italic>Cln3<\/jats:italic> mutation on development of autofluorescent storage material, gliosis, glucose metabolism, oxidative stress, and transmitter receptors during postnatal brain maturation, brain tissue of <jats:italic>Cln3<jats:sup>\u0394ex7\/8<\/jats:sup><\/jats:italic> mice at the ages of 3, 4, 5, 6, 9, and 19 months was subjected to immunocytochemistry to label gliotic markers and nitric oxide synthases; photometric assays to assess enzyme activities of glycolysis and antioxidative defense systems; and level of reactive nitrogen species as well as quantitative receptor autoradiography to detect select cholinergic, glutamatergic, and GABAergic receptor subtypes. The developmental increase in cerebral cortical autofluorescent lipofuscin\u2010like deposition is accompanied by a significant astro\u2010 and microgliosis, increased activities of lactate dehydrogenase and phosphofructokinase, decreased level of glutathione peroxidase, enhanced amount of reactive nitrogen species, and lowered binding levels of N\u2010methyl\u2010D\u2010aspartate\u2010 and M1\u2010muscarinic acetylcholine receptors in select brain regions but hardly in GABA<jats:sub>A<\/jats:sub> receptor sites compared with wild\u2010type mice. Detailed elucidation of the sequence of pathological events during postnatal development highlights new potential strategies for symptomatic treatment of the disease. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21630","type":"journal-article","created":{"date-parts":[[2008,2,9]],"date-time":"2008-02-09T00:46:21Z","timestamp":1202517981000},"page":"1857-1870","source":"Crossref","is-referenced-by-count":24,"title":["Developmental impairments of select neurotransmitter systems in brains of <i>Cln3<\/i><sup>\u0394<i>ex7\/8<\/i><\/sup> knock\u2010in mice, an animal model of juvenile neuronal ceroid lipofuscinosis"],"prefix":"10.1002","volume":"86","author":[{"given":"Philipp","family":"Herrmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Druckrey\u2010Fiskaaen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Kouznetsova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Heinitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Bigl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Cotman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Schliebs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,2,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1986.tb04604.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21416"},{"key":"e_1_2_7_4_1","series-title":"Methods of enzymatic analysis","author":"Bergmeyer HU","year":"1983"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67031164.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007020050174"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01273267"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00684808"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-006-9203-y"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602180200"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.12.1421"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.22.2709"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.14.6368"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02132.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-5-57"},{"key":"e_1_2_7_16_1","volume-title":"The mouse brain in stereotaxic coordinates","author":"Franklin KBJ","year":"1977"},{"key":"e_1_2_7_17_1","first-page":"211","article-title":"Clinical features and molecular genetic basis of the neuronal ceroid lipofuscinoses","volume":"89","author":"Gardiner RM","year":"2002","journal-title":"Adv Neurol"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2004.tb00499.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2000.3006"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/eipn.2000.0464"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19990801)57:3<388::AID-JNR11>3.0.CO;2-2"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.04.064"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0014-2956.2001.02530.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90274-0"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19990815)57:4<551::AID-JNR15>3.0.CO;2-R"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2136651100"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.3.10.2546848"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2002.16002.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-5748(01)00010-7"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.07.023"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E03-02-0120"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.05.007"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00901.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.19.2123"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh321"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02758-5"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03280-8"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00284-9"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1999.0267"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1998.0209"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1086\/514846"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20975"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36006-4"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320310618"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)83610-9"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420428"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(20000101)59:1<19::AID-JNR3>3.0.CO;2-Y"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/8861"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507380200"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.07.030"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.05.018"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(99)00007-7"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi406"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2000.4583"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.929"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02513-0"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)60012-6"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.12.006"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(97)00010-7"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-1166(1998120)13:12<840::AID-GPS877>3.0.CO;2-R"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1177\/019262330002800104"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.9.4350"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)80908-D"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2004.tb00077.x"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01127.x"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.21630","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.21630","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:34:13Z","timestamp":1697157253000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.21630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,8]]},"references-count":64,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2008,6]]}},"alternative-id":["10.1002\/jnr.21630"],"URL":"https:\/\/doi.org\/10.1002\/jnr.21630","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2,8]]}}}