{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:33:01Z","timestamp":1778617981116,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,6,9]],"date-time":"2005-06-09T00:00:00Z","timestamp":1118275200000},"content-version":"vor","delay-in-days":3657,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1995,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The pathogenesis of brain dysfunction in a canine model of juvenile Batten disease was studied with techniques designed to determine sequential changes in mitochondrial morphology and cytochrome oxidase (CO) activity, and in neurons and synapses using gamma\u2010aminobutyric acid (GABA) as a neurotransmitter. Histochemical and immunocytochemical methods were employed. Mitochondrial alterations were found in a select population of nonpyramidal neurons in neocortex and claustrum, and in cerebellar basket cells. Proportions of affected neurons at any one time remained constant over the disease course, with morphologically\u2010abnormal mitochondria first being recognized at age 6 months. Enlarged mitochondria were readily identifiable at the light microscope (LM) level as large CO\u2010positive or mitochondrial antibody\u2010positive granular structures. Colabelling with antibodies to GABA or to parvalbumin (PV) indicated that most of these cells were GABAergic. Ultrastructurally, atypical mitochondria were characterized by globular enlargement, intramitochondrial membranous inclusions, and disorganized internal structure. CO activity in all other cell somata and in neuropil was diminished compared with normal, age\u2010matched tissue. Glutamic acid decarboxylase (GAD), PV, and GABA studies demonstrated loss of GABAergic neurons and synapses in cortex and cerebellum of affected dogs. These results indicate that abnormal mitochondria are present in neurons in Batten disease, and suggest that suboptimal mitochondrial function may play a role in the pathogenic mechanisms of brain dysfunction in this disorder. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.1320570219","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T18:01:48Z","timestamp":1118512908000},"page":"204-212","source":"Crossref","is-referenced-by-count":31,"title":["Morphological alterations in neocortical and cerebellar GABAergic neurons in a canine model of juvenile Batten disease"],"prefix":"10.1002","volume":"57","author":[{"given":"Philip A.","family":"March","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Wurzelmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven U.","family":"Walkley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,6,9]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01273267"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00684808"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3945815"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/3.4.273"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320570229"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2680751"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-6610-6_3"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(72)90621-X"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420427"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0047-6374(73)90034-1"},{"key":"e_1_2_1_12_1","first-page":"132","volume-title":"Mitochondria Biogenesis and Breakdown.","author":"Luzikov VN"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199305000-00086"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/3.5.387"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(88)90765-2"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-5339-1_15"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420428"},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1523\/JNEUROSCI.02-12-01725.1982","article-title":"A preferential loss of GABAergic, symmetrical synapses in epileptic foci: a quantitative ultrastructural analysis of monkey neocortex","volume":"2","author":"Ribak CE","year":"1982","journal-title":"J Neurosci"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.38.1.1"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(08)60087-2"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320570218"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1977.00500170052010"},{"key":"e_1_2_1_23_1","first-page":"279","volume-title":"Cytochemical Methods in Neuroanatomy.","author":"Wu J\u2010Y","year":"1982"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687063"},{"key":"e_1_2_1_25_1","first-page":"519","volume-title":"Lysosomes and Storage Diseases.","author":"Zeman W","year":"1973"}],"container-title":["American Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.1320570219","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.1320570219","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T15:18:41Z","timestamp":1698333521000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.1320570219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,6,5]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1995,6,5]]}},"alternative-id":["10.1002\/ajmg.1320570219"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.1320570219","archive":["Portico"],"relation":{},"ISSN":["0148-7299","1096-8628"],"issn-type":[{"value":"0148-7299","type":"print"},{"value":"1096-8628","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,6,5]]}}}