Araştırma Makalesi
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Examination of Cognitive Functions and Hippocampal Synaptophysin Levels in an Experimental Schizophrenia Model

Yıl 2023, Cilt: 49 Sayı: 3, 367 - 373, 31.12.2023
https://doi.org/10.32708/uutfd.1381823

Öz

Schizophrenia is a chronic brain disease and is clinically characterized by positive, negative and cognitive symptoms. Cognitive symptoms can be observed starting from the prodromal period of the disease. The aim of this study is to investigate the cognitive functions of rats and hippocampal levels of the presynaptic protein synaptophysin in an experimental schizophrenia model created by prepulse-mediated inhibition (PPI) of the startle reflex. In the study, 30 male Wistar type rats were subjected to basal PPI measurements and were ranked from low to high according to these values. After the first 10 rats were divided into the "low" and the last 10 rats into the "high" inhibition group, they were subjected to the Morris Water Maze (MWM) test for 5 days. At the end of the test, the rats were sacrificed, hippocampus regions were excised, and the presynaptic synaptophysin protein was analyzed by Western Blot method. According to the results, while there was no difference between the learning levels of both groups, the frequency of memory functions frequency to cross the platform area (p <0.05) and time spent in the platform area (p <0.05) parameters were found to be significantly lower in rats in the low PPI group. Synaptophysin levels were similarly found to be significantly (p<0.01) lower in rats in the low PPI group. The results of our study show that some cognitive functions and presynaptic protein synaptophysin levels are significantly lower in rats with low PPI values compared to those with high PPI values. These results also supported the importance of the PPI test, which has been used as a reliable method in schizophrenia research for a long time, by emphasizing its comparable outcomes in human and animal studies of schizophrenia.

Proje Numarası

(Proje No: KUAP(T)-2020/1).

Kaynakça

  • 1. Schultz SH, North SW, Shields CG. Schizophrenia: A review. Am Fam Physician. 2007;75(12).
  • 2. Weickert CS, Weickert TW, Pillai A, Buckley PF. Biomarkers in schizophrenia: A brief conceptual consideration. Dis Markers. 2013;35(1):3-9. doi:10.1155/2013/510402
  • 3. Jones C, Watson D, Fone K. Animal models of schizophrenia. Br J Pharmacol. 2011;164(4):1162-1194. doi:10.1111/j.1476-5381.2011.01386.x
  • 4. Allen AJ, Griss ME, Folley BS, Hawkins KA, Pearlson GD. Endophenotypes in schizophrenia: A selective review. Schizophr Res. 2009;109(1-3):24-37. doi:10.1016/j.schres.2009.01.016
  • 5. Gould TD, Gottesman II. Psychiatric endophenotypes and the development of valid animal models. Genes, Brain Behav. 2006;5(2):113-119. doi:10.1111/j.1601-183X.2005.00186.x
  • 6. Parwani A, Duncan EJ, Bartlett E, et al. Impaired prepulse inhibition of acoustic startle in schizophrenia. Biol Psychiatry. 2000;47(7):662-669. doi:10.1016/S0006-3223(99)00148-1
  • 7. Mena A, Ruiz-Salas JC, Puentes A, Dorado I, Ruiz-Veguilla M, De la Casa LG. Reduced prepulse inhibition as a biomarker of schizophrenia. Front Behav Neurosci. 2016;10(OCT). doi:10.3389/fnbeh.2016.00202
  • 8. Osimo EF, Beck K, Reis Marques T, Howes OD. Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures. Mol Psychiatry. 2019;24(4):549-561. doi:10.1038/s41380-018-0041-5
  • 9. Catts VS, Derminio DS, Hahn CG, Weickert CS. Postsynaptic density levels of the NMDA receptor NR1 subunit and PSD-95 protein in prefrontal cortex from people with schizophrenia. npj Schizophr. 2015;1(1). doi:10.1038/npjschz.2015.37
  • 10. Sampedro-Viana D, Cañete T, Mourelo L, et al. Low prepulse inhibition predicts lower social interaction, impaired spatial working memory, reference memory and cognitive flexibility in genetically heterogeneous rats. Physiol Behav. 2023;271(May):114355. doi:10.1016/j.physbeh.2023.114355
  • 11. Oral S, Göktalay G. Prepulse inhibition based grouping of rats and assessing differences in response to pharmacological agents. Neurosci Lett. 2021;755. doi:10.1016/j.neulet.2021.135913
  • 12. Goren B, Cakir A, Ocalan B, et al. Long-term cognitive effects of uridine treatment in a neonatal rat model of hypoxic-ischemic encephalopathy. Brain Res. 2017;1659:81-87. doi:10.1016/j.brainres.2017.01.026
  • 13. Cansev M, Minbay Z, Goren B, et al. Neuroprotective effects of uridine in a rat model of neonatal hypoxic-ischemic encephalopathy. Neurosci Lett. 2013;542. doi:10.1016/j.neulet.2013.02.035
  • 14.Csomor PA, Yee BK, Feldon J, Theodoridou A, Studerus E, Vollenweider FX. Impaired prepulse inhibition and prepulse-elicited reactivity but intact reflex circuit excitability inunmedicated schizophrenia patients: A comparison with healthy subjects and medicated schizophrenia patients. Schizophr Bull. 2009;35(1):244-255. doi:10.1093/schbul/sbm146
  • 15.Hagan JJ, Jones DNC. Predicting drug efficacy for cognitive deficits in schizophrenia. In: Schizophrenia Bulletin. Vol 31. ; 2005:830-853. doi:10.1093/schbul/sbi058
  • 16.Bitsios P, Giakoumaki SG, Theou K, Frangou S. Increased prepulse inhibition of the acoustic startle response is associated with better strategy formation and execution times in healthy males. Neuropsychologia. 2006;44(12):2494-2499. doi:10.1016/j.neuropsychologia.2006.04.001
  • 17.Oliveras I, Río-Álamos C, Cañete T, et al. Prepulse inhibition predicts spatial working memory performance in the inbredRoman high- and low-avoidance rats and in genetically heterogeneous NIH-HS rats: Relevance for studying pre-attentive and cognitive anomalies in schizophrenia. Front Behav Neurosci. 2015;9(AUGUST).doi:10.3389/fnbeh.2015.00213
  • 18.Varty GB, Marsden CA, Higgins GA. Reduced synaptophysinimmunoreactivity in the dentate gyrus of prepulse inhibition-impaired isolation-reared rats. Brain Res. 1999;824(2):197-203. doi:10.1016/S0006-8993(99)01173-7
  • 19.Eastwood SL, Burnet PWJ, Harrison PJ. Altered synaptophysinexpression as a marker of synaptic pathology in schizophrenia. Neuroscience. 1995;66(2):309-319. doi:10.1016/0306-4522(94)00586-T
  • 20.Glantz LA, Lewis DA. Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia regional and diagnostic specificity. Arch Gen Psychiatry. 1997;54(10):943-952. doi:10.1001/archpsyc.1997.01830220065010
  • 21.Eastwood SL, Cairns NJ, Harrison PJ. Synaptophysin gene expression in schizophrenia: Investigation of synaptic pathology in the cerebral cortex. Br J Psychiatry. 2000;176(MAR.):236-242. doi:10.1192/bjp.176.3.236
  • 22.Hill JJ, Hashimoto T, Lewis DA. Molecular mechanisms contributing to dendritic spine alterations in the prefrontal cortex of subjects with schizophrenia. Mol Psychiatry. 2006;11(6):557-566. doi:10.1038/sj.mp.4001792
  • 23.Ide M, Lewis DA. Altered Cortical CDC42 Signaling Pathwaysin Schizophrenia: Implications for Dendritic Spine Deficits. Biol Psychiatry. 2010;68(1):25-32. doi:10.1016/j.biopsych.2010.02.016
  • 24.Karson CN, Mrak RE, Schluterman KO, Sturner WQ, ShengJG, Griffin WST. Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: A possible neurochemical basis for “hypofrontality.” Mol Psychiatry. 1999;4(1):39-45. doi:10.1038/sj.mp.4000459
  • 25.Sawada K, Young CE, Barr AM, et al. Alteredimmunoreactivity of complexin protein in prefrontal cortex in severe mental illness. Mol Psychiatry. 2002;7(5):484-492. doi:10.1038/sj.mp.4000978
  • 26.Tan ML, Dyck BA, Gabriele J, et al. Synapsin II geneexpression in the dorsolateral prefrontal cortex of brain specimens from patients with schizophrenia and bipolar disorder: Effect of lifetime intake of antipsychotic drugs. Pharmacogenomics J. 2014;14(1):63-69. doi:10.1038/tpj.2013.6
  • 27.Thompson PM, Sower AC, Perrone-Bizzozero NI. Altered levels of the synaptosomal associated protein SNAP-25 inschizophrenia. Biol Psychiatry. 1998;43(4):239-243. doi:10.1016/S0006-3223(97)00204-7
  • 28.Varea E, Guirado R, Gilabert-Juan J, et al. Expression of PSA-NCAM and synaptic proteins in the amygdala of psychiatric disorder patients. J Psychiatr Res. 2012;46(2):189-197. doi:10.1016/j.jpsychires.2011.10.011
  • 29.Webster MJ, Shannon Weickert C, Herman MM, Hyde TM, Kleinman JE. Synaptophysin and GAP-43 mRNA levels in the hippocampus of subjects with schizophrenia. Schizophr Res. 2001;49(1-2):89-98. doi:10.1016/S0920-9964(00)00052-9
  • 30.Egbujo CN, Sinclair D, Hahn CG. Dysregulations of Synaptic Vesicle Trafficking in Schizophrenia. Curr Psychiatry Rep. 2016;18(8). doi:10.1007/s11920-016-0710-5
  • 31.Anzalone A, Lizardi-Ortiz JE, Ramos M, et al. Dual control ofdopamine synthesis and release by presynaptic and postsynaptic dopamine D2 receptors. J Neurosci. 2012;32(26):9023-9024. doi:10.1523/JNEUROSCI.0918-12.2012
  • 32.Antonucci F, Corradini I, Morini R, et al. Reduced SNAP-25 alters short-term plasticity at developing glutamatergic synapses. EMBO Rep. 2013;14(7):645-651. doi:10.1038/embor.2013.75
  • 33.Brunelin J, Fecteau S, Suaud-Chagny M-F. Abnormal Striatal Dopamine Transmission in Schizophrenia. Curr Med Chem. 2013;20(3):397-404. doi:10.2174/0929867311320030011

Deneysel Şizofreni Modelinde Bilişsel Fonksiyonlar ve Hipokampal Sinaptofizin Düzeylerinin İncelenmesi

Yıl 2023, Cilt: 49 Sayı: 3, 367 - 373, 31.12.2023
https://doi.org/10.32708/uutfd.1381823

Öz

Şizofreni pozitif, negatif ve bilişsel belirtiler ile seyreden kronik bir beyin hastalığıdır. Bilişsel belirtiler hastalığın prodromal döneminden itibaren gözlenebilmektedir. Bu çalışmanın amacı irkilme refleksininin ön uyaran aracılı inhibisyonu (ÖUAİ) ile oluşturulan deneysel şizofreni modelinde sıçanların bilişsel fonksiyonlarını ve hipokampal presinaptik proteinlerden sinaptofizin düzeylerini araştırmaktır. Çalışmada 30 adet erkek Wistar türü sıçanlar bazal ÖUAİ ölçümüne tabi tutulmuş ve bu değerlere göre düşükten yükseğe sıralanmıştır. İlk 10 sıçan “düşük” ve son 10 sıçan “yüksek” inhibisyonlu grup olarak ayrıldıktan sonra 5 gün boyunca Morris Su Tankı (MST) testine tabi tutulmuştur. Testin bitiminde sıçanlar sakrifiye edilerek hipokampus bölgeleri eksize edilmiş ve hipokampal presinaptik proteinlerden sinaptofizin Western Blot yöntemiyle analiz edilmiştir. Sonuçlara göre her iki grubun öğrenme düzeyleri arasında fark bulunmaz iken ve hafıza fonksiyonlarının platform alanından geçme sıklığı (p<0,05) ve platform alanında geçirilen süre parametreleri (p<0,05) düşük ÖUAİ gruptaki sıçanlarda anlamlı olarak daha düşük bulunmuştur. Sinaptofizin düzeyleri de benzer şekilde düşük ÖUAİ grubundaki sıçanlarda anlamlı olarak (p<0,01) düşük tespit edilmiştir. Çalışmamızın sonuçları yüksek ÖUAİ değerine sahip sıçanlarla kıyaslandığında ÖUAİ değerleri düşük olan sıçanların bazı bilişsel fonksiyonlarının ve hipokampal presinaptik proteinlerden sinaptofizin düzeylerinin anlamlı olarak daha düşük olduğunu göstermektedir. Bu sonuçlar aynı zamanda uzun zamandır şizofreni çalışmalarında güvenilir bir yöntem olarak kullanılan ÖUAİ testinin insan ve hayvan çalışmalarındaki benzer sonuçlarına vurgu yaparak şizofreni araştırmalarındaki önemini desteklemiştir.

Etik Beyan

Deneysel çalışmalar için Bursa Uludağ Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu’ndan onay alınmıştır (Onay No: 2019 - 04 / 04).

Destekleyen Kurum

Bu çalışma Bursa Uludağ Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından desteklenmiştir

Proje Numarası

(Proje No: KUAP(T)-2020/1).

Teşekkür

Bu çalışmada verdikleri destek için Bursa Uludağ Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimine teşekkür ederiz

Kaynakça

  • 1. Schultz SH, North SW, Shields CG. Schizophrenia: A review. Am Fam Physician. 2007;75(12).
  • 2. Weickert CS, Weickert TW, Pillai A, Buckley PF. Biomarkers in schizophrenia: A brief conceptual consideration. Dis Markers. 2013;35(1):3-9. doi:10.1155/2013/510402
  • 3. Jones C, Watson D, Fone K. Animal models of schizophrenia. Br J Pharmacol. 2011;164(4):1162-1194. doi:10.1111/j.1476-5381.2011.01386.x
  • 4. Allen AJ, Griss ME, Folley BS, Hawkins KA, Pearlson GD. Endophenotypes in schizophrenia: A selective review. Schizophr Res. 2009;109(1-3):24-37. doi:10.1016/j.schres.2009.01.016
  • 5. Gould TD, Gottesman II. Psychiatric endophenotypes and the development of valid animal models. Genes, Brain Behav. 2006;5(2):113-119. doi:10.1111/j.1601-183X.2005.00186.x
  • 6. Parwani A, Duncan EJ, Bartlett E, et al. Impaired prepulse inhibition of acoustic startle in schizophrenia. Biol Psychiatry. 2000;47(7):662-669. doi:10.1016/S0006-3223(99)00148-1
  • 7. Mena A, Ruiz-Salas JC, Puentes A, Dorado I, Ruiz-Veguilla M, De la Casa LG. Reduced prepulse inhibition as a biomarker of schizophrenia. Front Behav Neurosci. 2016;10(OCT). doi:10.3389/fnbeh.2016.00202
  • 8. Osimo EF, Beck K, Reis Marques T, Howes OD. Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures. Mol Psychiatry. 2019;24(4):549-561. doi:10.1038/s41380-018-0041-5
  • 9. Catts VS, Derminio DS, Hahn CG, Weickert CS. Postsynaptic density levels of the NMDA receptor NR1 subunit and PSD-95 protein in prefrontal cortex from people with schizophrenia. npj Schizophr. 2015;1(1). doi:10.1038/npjschz.2015.37
  • 10. Sampedro-Viana D, Cañete T, Mourelo L, et al. Low prepulse inhibition predicts lower social interaction, impaired spatial working memory, reference memory and cognitive flexibility in genetically heterogeneous rats. Physiol Behav. 2023;271(May):114355. doi:10.1016/j.physbeh.2023.114355
  • 11. Oral S, Göktalay G. Prepulse inhibition based grouping of rats and assessing differences in response to pharmacological agents. Neurosci Lett. 2021;755. doi:10.1016/j.neulet.2021.135913
  • 12. Goren B, Cakir A, Ocalan B, et al. Long-term cognitive effects of uridine treatment in a neonatal rat model of hypoxic-ischemic encephalopathy. Brain Res. 2017;1659:81-87. doi:10.1016/j.brainres.2017.01.026
  • 13. Cansev M, Minbay Z, Goren B, et al. Neuroprotective effects of uridine in a rat model of neonatal hypoxic-ischemic encephalopathy. Neurosci Lett. 2013;542. doi:10.1016/j.neulet.2013.02.035
  • 14.Csomor PA, Yee BK, Feldon J, Theodoridou A, Studerus E, Vollenweider FX. Impaired prepulse inhibition and prepulse-elicited reactivity but intact reflex circuit excitability inunmedicated schizophrenia patients: A comparison with healthy subjects and medicated schizophrenia patients. Schizophr Bull. 2009;35(1):244-255. doi:10.1093/schbul/sbm146
  • 15.Hagan JJ, Jones DNC. Predicting drug efficacy for cognitive deficits in schizophrenia. In: Schizophrenia Bulletin. Vol 31. ; 2005:830-853. doi:10.1093/schbul/sbi058
  • 16.Bitsios P, Giakoumaki SG, Theou K, Frangou S. Increased prepulse inhibition of the acoustic startle response is associated with better strategy formation and execution times in healthy males. Neuropsychologia. 2006;44(12):2494-2499. doi:10.1016/j.neuropsychologia.2006.04.001
  • 17.Oliveras I, Río-Álamos C, Cañete T, et al. Prepulse inhibition predicts spatial working memory performance in the inbredRoman high- and low-avoidance rats and in genetically heterogeneous NIH-HS rats: Relevance for studying pre-attentive and cognitive anomalies in schizophrenia. Front Behav Neurosci. 2015;9(AUGUST).doi:10.3389/fnbeh.2015.00213
  • 18.Varty GB, Marsden CA, Higgins GA. Reduced synaptophysinimmunoreactivity in the dentate gyrus of prepulse inhibition-impaired isolation-reared rats. Brain Res. 1999;824(2):197-203. doi:10.1016/S0006-8993(99)01173-7
  • 19.Eastwood SL, Burnet PWJ, Harrison PJ. Altered synaptophysinexpression as a marker of synaptic pathology in schizophrenia. Neuroscience. 1995;66(2):309-319. doi:10.1016/0306-4522(94)00586-T
  • 20.Glantz LA, Lewis DA. Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia regional and diagnostic specificity. Arch Gen Psychiatry. 1997;54(10):943-952. doi:10.1001/archpsyc.1997.01830220065010
  • 21.Eastwood SL, Cairns NJ, Harrison PJ. Synaptophysin gene expression in schizophrenia: Investigation of synaptic pathology in the cerebral cortex. Br J Psychiatry. 2000;176(MAR.):236-242. doi:10.1192/bjp.176.3.236
  • 22.Hill JJ, Hashimoto T, Lewis DA. Molecular mechanisms contributing to dendritic spine alterations in the prefrontal cortex of subjects with schizophrenia. Mol Psychiatry. 2006;11(6):557-566. doi:10.1038/sj.mp.4001792
  • 23.Ide M, Lewis DA. Altered Cortical CDC42 Signaling Pathwaysin Schizophrenia: Implications for Dendritic Spine Deficits. Biol Psychiatry. 2010;68(1):25-32. doi:10.1016/j.biopsych.2010.02.016
  • 24.Karson CN, Mrak RE, Schluterman KO, Sturner WQ, ShengJG, Griffin WST. Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: A possible neurochemical basis for “hypofrontality.” Mol Psychiatry. 1999;4(1):39-45. doi:10.1038/sj.mp.4000459
  • 25.Sawada K, Young CE, Barr AM, et al. Alteredimmunoreactivity of complexin protein in prefrontal cortex in severe mental illness. Mol Psychiatry. 2002;7(5):484-492. doi:10.1038/sj.mp.4000978
  • 26.Tan ML, Dyck BA, Gabriele J, et al. Synapsin II geneexpression in the dorsolateral prefrontal cortex of brain specimens from patients with schizophrenia and bipolar disorder: Effect of lifetime intake of antipsychotic drugs. Pharmacogenomics J. 2014;14(1):63-69. doi:10.1038/tpj.2013.6
  • 27.Thompson PM, Sower AC, Perrone-Bizzozero NI. Altered levels of the synaptosomal associated protein SNAP-25 inschizophrenia. Biol Psychiatry. 1998;43(4):239-243. doi:10.1016/S0006-3223(97)00204-7
  • 28.Varea E, Guirado R, Gilabert-Juan J, et al. Expression of PSA-NCAM and synaptic proteins in the amygdala of psychiatric disorder patients. J Psychiatr Res. 2012;46(2):189-197. doi:10.1016/j.jpsychires.2011.10.011
  • 29.Webster MJ, Shannon Weickert C, Herman MM, Hyde TM, Kleinman JE. Synaptophysin and GAP-43 mRNA levels in the hippocampus of subjects with schizophrenia. Schizophr Res. 2001;49(1-2):89-98. doi:10.1016/S0920-9964(00)00052-9
  • 30.Egbujo CN, Sinclair D, Hahn CG. Dysregulations of Synaptic Vesicle Trafficking in Schizophrenia. Curr Psychiatry Rep. 2016;18(8). doi:10.1007/s11920-016-0710-5
  • 31.Anzalone A, Lizardi-Ortiz JE, Ramos M, et al. Dual control ofdopamine synthesis and release by presynaptic and postsynaptic dopamine D2 receptors. J Neurosci. 2012;32(26):9023-9024. doi:10.1523/JNEUROSCI.0918-12.2012
  • 32.Antonucci F, Corradini I, Morini R, et al. Reduced SNAP-25 alters short-term plasticity at developing glutamatergic synapses. EMBO Rep. 2013;14(7):645-651. doi:10.1038/embor.2013.75
  • 33.Brunelin J, Fecteau S, Suaud-Chagny M-F. Abnormal Striatal Dopamine Transmission in Schizophrenia. Curr Med Chem. 2013;20(3):397-404. doi:10.2174/0929867311320030011
Toplam 33 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sinirbilim (Diğer)
Bölüm Özgün Araştırma Makaleleri
Yazarlar

Erkan Ermiş 0000-0001-5359-3477

Cansu Koç 0000-0002-6097-5585

Hilmiye Şule Mergen 0000-0001-7589-2013

İbrahim Makinecioğlu 0000-0002-7637-0994

Ayşe Pınar Vural 0000-0002-3358-0019

Mehmet Cansev 0000-0003-2918-5064

Gökhan Göktalay 0000-0001-6261-4233

Şafak Eray Çamlı 0000-0002-4847-7751

Proje Numarası (Proje No: KUAP(T)-2020/1).
Yayımlanma Tarihi 31 Aralık 2023
Gönderilme Tarihi 30 Ekim 2023
Kabul Tarihi 1 Aralık 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 49 Sayı: 3

Kaynak Göster

APA Ermiş, E., Koç, C., Mergen, H. Ş., Makinecioğlu, İ., vd. (2023). Deneysel Şizofreni Modelinde Bilişsel Fonksiyonlar ve Hipokampal Sinaptofizin Düzeylerinin İncelenmesi. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 49(3), 367-373. https://doi.org/10.32708/uutfd.1381823
AMA Ermiş E, Koç C, Mergen HŞ, Makinecioğlu İ, Vural AP, Cansev M, Göktalay G, Eray Çamlı Ş. Deneysel Şizofreni Modelinde Bilişsel Fonksiyonlar ve Hipokampal Sinaptofizin Düzeylerinin İncelenmesi. Uludağ Tıp Derg. Aralık 2023;49(3):367-373. doi:10.32708/uutfd.1381823
Chicago Ermiş, Erkan, Cansu Koç, Hilmiye Şule Mergen, İbrahim Makinecioğlu, Ayşe Pınar Vural, Mehmet Cansev, Gökhan Göktalay, ve Şafak Eray Çamlı. “Deneysel Şizofreni Modelinde Bilişsel Fonksiyonlar Ve Hipokampal Sinaptofizin Düzeylerinin İncelenmesi”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 49, sy. 3 (Aralık 2023): 367-73. https://doi.org/10.32708/uutfd.1381823.
EndNote Ermiş E, Koç C, Mergen HŞ, Makinecioğlu İ, Vural AP, Cansev M, Göktalay G, Eray Çamlı Ş (01 Aralık 2023) Deneysel Şizofreni Modelinde Bilişsel Fonksiyonlar ve Hipokampal Sinaptofizin Düzeylerinin İncelenmesi. Uludağ Üniversitesi Tıp Fakültesi Dergisi 49 3 367–373.
IEEE E. Ermiş, C. Koç, H. Ş. Mergen, İ. Makinecioğlu, A. P. Vural, M. Cansev, G. Göktalay, ve Ş. Eray Çamlı, “Deneysel Şizofreni Modelinde Bilişsel Fonksiyonlar ve Hipokampal Sinaptofizin Düzeylerinin İncelenmesi”, Uludağ Tıp Derg, c. 49, sy. 3, ss. 367–373, 2023, doi: 10.32708/uutfd.1381823.
ISNAD Ermiş, Erkan vd. “Deneysel Şizofreni Modelinde Bilişsel Fonksiyonlar Ve Hipokampal Sinaptofizin Düzeylerinin İncelenmesi”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 49/3 (Aralık 2023), 367-373. https://doi.org/10.32708/uutfd.1381823.
JAMA Ermiş E, Koç C, Mergen HŞ, Makinecioğlu İ, Vural AP, Cansev M, Göktalay G, Eray Çamlı Ş. Deneysel Şizofreni Modelinde Bilişsel Fonksiyonlar ve Hipokampal Sinaptofizin Düzeylerinin İncelenmesi. Uludağ Tıp Derg. 2023;49:367–373.
MLA Ermiş, Erkan vd. “Deneysel Şizofreni Modelinde Bilişsel Fonksiyonlar Ve Hipokampal Sinaptofizin Düzeylerinin İncelenmesi”. Uludağ Üniversitesi Tıp Fakültesi Dergisi, c. 49, sy. 3, 2023, ss. 367-73, doi:10.32708/uutfd.1381823.
Vancouver Ermiş E, Koç C, Mergen HŞ, Makinecioğlu İ, Vural AP, Cansev M, Göktalay G, Eray Çamlı Ş. Deneysel Şizofreni Modelinde Bilişsel Fonksiyonlar ve Hipokampal Sinaptofizin Düzeylerinin İncelenmesi. Uludağ Tıp Derg. 2023;49(3):367-73.

ISSN: 1300-414X, e-ISSN: 2645-9027

Uludağ Üniversitesi Tıp Fakültesi Dergisi "Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License" ile lisanslanmaktadır.


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2023