аЯрЁБс>ўџ 46ўџџџ3џџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџьЅСo@№ПZ"bjbj p p .$oo џџџџџџˆ’’’’’’’ІЮЮЮЮъ І~ ЖЭЯЯЯЯЯЯ$4 R† (ѓE’)))ѓ’’8 }}})’’Э})Э}(}Ѕ’’Ѕі  ж'TшЮЧЮ)@ЅЭN 0~ ЅЎ i Ў ЅІІ’’’’Ў ’Ѕ(ЎА|},d™ѓѓІІЄJ„s ІІJTIME COURSE OF AMYLOID BETA PATHOLOGY IN STREPTOZOTOCIN-RAT MODEL OF SPORADIC ALZHEIMER'S DISEASE Salkovic-Petrisic M 1, Osmanovic J 1, Hoyer S 2, Riederer P 3 1 Department of Pharmacology and Croatian Institute for Brain Research, Medical School, University of Zagreb, Croatia 2 Department of Pathology, University of Heidelberg, Germany 3 Department of Clinical Neurochemistry, Clinic for Psychiatry and Psychotherapy, University of Wќrzburg Objectives: Modelling of Alzheimer’s disease usually involves transgenic mice models which represent early onset familiar type of Alzheimer s disease (AD) for which pathological assemblies of amyloid beta (AВ) are thought to be the primary cause. Streptozotocin-intracerebroventricularly (STZ-icv) treated rats have been recognized as an experimental model for more frequent sporadic type of AD (sAD) which share with humans similarities of impaired brain insulin receptor (IR) signalling. We aimed to investigate the six month long time course of possible pathological changes of beta amyloid following the brain damage induced by STZ-icv treatment in rats. Methods. Male Wistar rats (3-4 month old) were sacrifice one, three or six months after STZ-icv treatment (1-3 mg/kg). Congo red staining and AВ 1-42 immunohistochemistry analyses were done on fixative-perfused, paraffin-embedded brain sections. Cognitive functions were tested in Morris Water Maze Test. Cruscal-Walles ANOVA and Mann-Whitney U test (P<0.05) were used. Results. One month after STZ-icv treatment no changes of AВ were observed, while congophilic AВ aggregates in meningeal capillaries which gave autoflorescence green light in cross-polarized light, and intracellular AВ1-42 accumulation in hippocampus/cerebral cortex were found after three months. In these regions AВ1-42 signal revealed primitive plaques formation six months following the STZ-icv treatment. Cognitive deficits, observed already after one month, persisted along the experiment. Conclusions. Results demonstrate the sequence buvx…†‘žŸ ЁЂ    R ќылЪлЪлЪлЪЗЂ|jZE1&h™#.CJOJQJ^JmH nHsH tH)h™#.CJH*OJQJ^JmH nHsH tHh™#.CJOJQJ^JmH sH "h™#.0JCJOJQJ^JmH sH %h™#.0J5CJOJQJ^JmH sH %h™#.0J5CJOJQJ^JmH sH (h™#.0J5CJH*OJQJ^JmH sH $hдZ$h™#.CJOJQJ^JmH sH !h™#.CJH*OJQJ^JmH sH h™#.CJOJQJ^JmH sH !h™#.>*CJOJQJ^JmH sH h™#.b  S М Н P ЦЄц!V"X"Z"їыыыыїыыыыїцфgd™#. $ Ц,a$gd™#.$a$gd™#. Z"ўR S U Ѕ Л М Н Ш x P X Ё К Цжx€œК>HЄИК№пЫЛЫЅ‘~g‘~Л~S~‘~S~Л~S~‘B!h™#.5CJOJQJ^JmH sH 'h™aЮh™#.CJH*OJQJ^JmH sH -h™aЮh™#.B*CJOJQJ^JmH phsH $h™aЮh™#.CJOJQJ^JmH sH 'h™aЮh™#.5CJOJQJ^JmH sH *h™#.CJOJQJ^JaJmH nHsH tHh™#.CJOJQJ^JmH sH &h™#.CJOJQJ^JmH nH sH tH !h™#.CJH*OJQJ^JmH sH h™#.CJOJQJ^JmH sH КМОР N$ & ц!T"X"Z"ыиШиЦиШиШиГЏЋhЂ2h™#.%h™#.6CJOJQJ^JaJmH sH Uh™#.CJOJQJ^JmH sH $h™aЮh™#.CJOJQJ^JmH sH 'h™aЮh™#.5CJOJQJ^JmH sH  of AВ pathology development starting in capillaries, moving to intracellular and finally extracellular accumulation and primitive plaque formation with the duration of period after the brain damage induced by betycytotoxic drug streptozotocin. Since STZ-icv treatment induces insulin resistant brain state (IRBS) in rats, these results provide evidence that IRBS could be a pathological core in generation of sAD preceding and triggering AВ plaque development and tau protein hyperphosphorylation. Supported by Croatian MZOS (108-1080003-0020) and DAAD. ,1hА‚. АЦA!А‰"А‰#‰$‰%ААФАФ Фœ@`ёџ@ ™#.NormalCJ_HaJmHsHtHDA@ђџЁD Default Paragraph FontRi@ѓџГR  Table Normalі4ж l4жaі (k@єџС(No List2B`ђ2 ™#. Body TextaJ*W`Ђ* ™#.Strong5\ $џџџџb SМНPТБв  ˜0€€˜0€€˜0€€˜0€€˜0€€˜0€€˜0€€˜0€€˜0€€˜0€€˜0€€˜0€€˜0€€b SНPТБв  |00€|00€|00€|00€|00€|00€|00€}|00€}|00€}|00€@0X 0ы$g8 R КZ" Z" Z" џџ "п„„ф!#п„ќ3$п„tћ%п„L^&п„мФ"'п„t@"(п„)п„Д="*п„+п„д8,п„ФN-п„Дћшш№јј11KЅЅГ    яіі IRRЏЛЛ   8*€urn:schemas-microsoft-com:office:smarttags€City€= *€urn:schemas-microsoft-com:office:smarttags €PlaceType€= *€urn:schemas-microsoft-com:office:smarttags €PlaceName€B*€urn:schemas-microsoft-com:office:smarttags€country-region€9 *€urn:schemas-microsoft-com:office:smarttags€place€    aPXТЪБНв  3333  џџMelita SalkovicхЂ2™#.=Pœѓџ@€ •- @пп P@P P@PPџџUnknownџџџџџџџџџџџџGю‡z €џTimes New Roman5€Symbol3&ю ‡z €џArial"1ˆ№ФЉЭЗfЭЗfС№‰‰ДД24   3ƒq№H)№џ?тџџџџџџџџџџџџџџџџџџџџџ=PџџaTIME COURSE OF AMYLOID BETA PATHOLOGY IN STREPTOZOTOCIN-RAT MODEL OF SPORADIC ALZHEIMER'S DISEASEMelita SalkovicMelita Salkovicўџр…ŸђљOhЋ‘+'Гй0д˜(4@P ht  œ ЈДМФЬтbTIME COURSE OF AMYLOID BETA PATHOLOGY IN STREPTOZOTOCIN-RAT MODEL OF SPORADIC ALZHEIMER'S DISEASEIIMEMelita SalkovicelieliNormalSMelita Salkovic2liMicrosoft Word 10.0@FУ#@ќш!шЮЧ@BЌEшЮЧўџеЭеœ.“—+,љЎ0X hpŒ”œЄ ЌДМФ Ь :тMedicinski fakultet { bTIME COURSE OF AMYLOID BETA PATHOLOGY IN STREPTOZOTOCIN-RAT MODEL OF SPORADIC ALZHEIMER'S DISEASE Title ўџџџўџџџ !"ўџџџ$%&'()*ўџџџ,-./012ўџџџ§џџџ5ўџџџўџџџўџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџRoot Entryџџџџџџџџ РF [FTшЮЧ7€Data џџџџџџџџџџџџ1TableџџџџWordDocumentџџџџ.$SummaryInformation(џџџџџџџџџџџџ#DocumentSummaryInformation8џџџџџџџџ+CompObjџџџџџџџџџџџџjџџџџџџџџџџџџўџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџўџ џџџџ РFMicrosoft Word Document MSWordDocWord.Document.8є9Вq