Bipolar I bozukluğunda bakteriyel translokasyon belirteç düzeylerinin değerlendirilmesi
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Dosyalar
Tarih
2019
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/embargoedAccess
Özet
Bipolar bozukluk genel popülasyonda sık gözlenmekte olup en fazla işgücü kaybına yol açan 10 hastalıktan biridir. Bipolar bozukluğun etiyolojisi henüz aydınlatılamamış olup son zamanlarda bipolar bozuklukta sistemik ve nöroinflamasyonun üzerinde durulmaktadır. Yapılan araştırmalarda santral sinir sistemi hastalıklarında özellikle inflamasyonun kaynağı olarak bakteriyel translokasyonun üzerinde durulmaktadır. Araştırmamızda bipolar bozuklukta gözlenen inflamasyonun kaynağının bakteriyel translokasyon olabileceği hipotezi ile bipolar bozukluk ötimik hastalarla sağlıklı kontrolleri bakteriyel translokasyon belirteçleri olan lipoprotein bağlayıcı protein, çözünebilen küme farklanma molekülü 14, Toll benzeri reseptör-4 gen ekspresyon düzeylerini karşılaştırdık. Ayrıca sistemik inflamatuvar belirteçler olan tümör nekroz faktör-? ve interlökin-1ß gen ekspresyon düzeylerini de gruplar arasında karşılaştırdık. Bakteriyel translokayonun stresle ilişkisi nedeniyle kortikotropin salgılatıcı faktör gen ekspresyon düzeylerini, Toll benzeri reseptör-4’ün uyarılması sonucu aktive olan nükleer faktör-?B gen ekspresyonlarını ve bipolar bozuklukda nöroprogresyonda rolü olan beyin kaynaklı nörotrofik faktör gen ekspresyon düzeylerini de bipolar bozukluk ötimik hastalarla sağlıklı kontrol grubu arasında karşılaştırdık. Araştırmaya Mental Bozuklukların Tanısal ve Sayımsal El Kitabı -5’e göre bipolar I bozukluk tanısı olan atak dönemi sonrasında en az 8 hafta süreyle hastalık belirtileri olmayan (remisyon) 56 hasta ile 53 sağlıklı gönüllü dahil edilmiştir. Tüm katılımcılardan kan alınarak bakteriyel translokasyon belirteçleri olan lipoprotein bağlayıcı protein, çözünebilen küme farklanma molekülü 14 ve Toll benzeri reseptör-4 düzeyleri ile inflamasyon kaskadında rol alan nükleer faktör-?B, tümör nekroz faktör-?, interlökin-1ß, beyindeki etkilerini saptayabilmek amacıyla beyin kaynaklı nörotrofik faktör ve stres ile ilişki hormon olan kortikotropin salgılatıcı hormonun mesajcı ribonükleik asit ekspreyon düzeyleri kantitatif eş zamanlı polimeraz zincir reaksiyonu ile ölçülmüştür. Sonuç olarak bipolar bozukluk ötimik hastalarda bakteriyel translokasyon belirteçleri olan lipoprotein bağlayıcı protein, çözünebilen küme farklanma molekülü 14, Toll benzeri reseptör-4 gen ekspresyon düzeylerinin sağlıklı kontrollerden anlamlı yüksek olduğunu saptadık. Bu bulgu bize BB’da gözlenen inflamasyonun kaynağının bakteriyel translokasyon olabileceğini düşündürmektedir. Toll benzeri reseptör-4’ün bipolar bozuklukta gözlenen nöroinflamasyonu mikroglia ve astrositleri aktive ederek tetiklediği bilinmektedir. BB ötimik hastalarda Toll benzeri reseptör-4 gen ekspresyonunun yüksek saptanması bipolar bozuklukta gözlenen nöroinflamasyonun kaynağının bakteriyel translokasyon olabileceği fikrini desteklemektedir. Araştırmamızda Toll benzeri reseptör-4 ile aktive olan nükleer faktör-?B gen ekspresyon düzeyleri de BB ötimik grupta yüksek bulunmuş olup inflamatuvar yolağın aktive olduğunu göstermektedir. Sistemik inflamatuvar belirteçler olan tümör nekroz faktörve interlökin-1ß gen ekspresyon düzeyleri gruplar arasında anlamlı farklılık göstermemiştir. Bu bulgu bipolar bozukluk ötimik hastaların kullandığı psikotrop ilaçlar sebebiyle düzeylerinin baskılanmasından kaynaklanıyor olabilir. Bütün bu bulgular bipolar bozuklukta gözlenen sistemik ve nöroinflamatuvar süreçlerde bakteriyel translokasyonun katkısı olduğunu düşündürmektedir.
Bipolar disorder is a common disease in the general population and is one of the top 10 diseases that causes disability. Although the etiology of bipolar disorder has not yet been elucidated, systemic and neuroinflammation could take place in the neuroprogression of the bipolar disorder. Most recently researches points out that bacterial translocation could be the source of systemic and neuroinflammation. In our study; we compared the levels of lipopolysaccharide binding protein, soluble cluster of differentitation 14 and Toll-like reseptör-4 gene expressions, which are markers of bacterial translocation, in bipolar disorder euthymic patients with healthy controls, according to the hypothesis that suggests bacterial translocation could be the source of systemic and neuroinflammation that observed in bipolar disorder patients. We also compared tumor necrosis factor and interleukin-1ß gene expression levels, which are systemic inflammatory markers, between the groups. Because of the relationship between bacterial translocation and stress, we compared corticotropin-releasing hormone gene expression levels between the groups. Moreover, we compared brain-derived neurotrophic factor gene expression levels, which has role in the neuroprogression of bipolar disorder and nuclear factor-kappa B gene expression levels, that is activated by Toll-like reseptör-4, between the groups. In this research we included 53 healthy volunteers and 56 patients with no disease symptoms (remission) for at least 8 weeks after the episode of bipolar I disorder according to Diagnostic and Statistical Manual of Mental Disorders-5 criterias. To compare the gene expression levels of lipopolysaccharide binding protein, soluble cluster of differentitation 14, Toll-like reseptör-4 (bacterial translocation markers), nuclear factor-kappa B, tumor necrosis factor-?, interleukin-1ß (systemic inflammatory markers), brain-derived neurotrophic factor (neurotrophic factor) and corticotropin-releasing hormone (stress- related gene), we used the quantitative real time polymerase chain reaction method. In conclusion, we found that gene expression levels of bacterial translocation markers (lipopolysaccharide binding protein, soluble cluster of differentitation 14 and Toll-like reseptör-4) were significantly higher in bipolar disorder group than the healthy volunteers. This finding suggests that bacterial translocation could be the reason of systemic inflammation which observed in bipolar disorder patients. It is also known that Toll-like reseptör-4 triggers neuroinflammation in bipolar disorder patients by activating microglia and astrocytes. High levels of Toll-like reseptör-4 gene expression in bipolar disorder patients in our research supports that the source of neuroinflammation in bipolar disorder patients might be bacterial translocation. In our research, nuclear factor-kappa B gene expression levels, activated by Toll-like reseptör-4, were higher in bipolar disorder euthymic group, indicated that the inflammatory pathway was active in this group. Tumor necrosis factor-? and interleukin-1ß gene expression levels did not differ significantly between the groups. This finding could be accompanied by the psychotropic drugs which was used to treat bipolar disorder euthymic group. In general, all these findings support that bacterial translocation pathway contributes to the systemic and neuroinflammation in bipolar disorder pathophysiology.
Bipolar disorder is a common disease in the general population and is one of the top 10 diseases that causes disability. Although the etiology of bipolar disorder has not yet been elucidated, systemic and neuroinflammation could take place in the neuroprogression of the bipolar disorder. Most recently researches points out that bacterial translocation could be the source of systemic and neuroinflammation. In our study; we compared the levels of lipopolysaccharide binding protein, soluble cluster of differentitation 14 and Toll-like reseptör-4 gene expressions, which are markers of bacterial translocation, in bipolar disorder euthymic patients with healthy controls, according to the hypothesis that suggests bacterial translocation could be the source of systemic and neuroinflammation that observed in bipolar disorder patients. We also compared tumor necrosis factor and interleukin-1ß gene expression levels, which are systemic inflammatory markers, between the groups. Because of the relationship between bacterial translocation and stress, we compared corticotropin-releasing hormone gene expression levels between the groups. Moreover, we compared brain-derived neurotrophic factor gene expression levels, which has role in the neuroprogression of bipolar disorder and nuclear factor-kappa B gene expression levels, that is activated by Toll-like reseptör-4, between the groups. In this research we included 53 healthy volunteers and 56 patients with no disease symptoms (remission) for at least 8 weeks after the episode of bipolar I disorder according to Diagnostic and Statistical Manual of Mental Disorders-5 criterias. To compare the gene expression levels of lipopolysaccharide binding protein, soluble cluster of differentitation 14, Toll-like reseptör-4 (bacterial translocation markers), nuclear factor-kappa B, tumor necrosis factor-?, interleukin-1ß (systemic inflammatory markers), brain-derived neurotrophic factor (neurotrophic factor) and corticotropin-releasing hormone (stress- related gene), we used the quantitative real time polymerase chain reaction method. In conclusion, we found that gene expression levels of bacterial translocation markers (lipopolysaccharide binding protein, soluble cluster of differentitation 14 and Toll-like reseptör-4) were significantly higher in bipolar disorder group than the healthy volunteers. This finding suggests that bacterial translocation could be the reason of systemic inflammation which observed in bipolar disorder patients. It is also known that Toll-like reseptör-4 triggers neuroinflammation in bipolar disorder patients by activating microglia and astrocytes. High levels of Toll-like reseptör-4 gene expression in bipolar disorder patients in our research supports that the source of neuroinflammation in bipolar disorder patients might be bacterial translocation. In our research, nuclear factor-kappa B gene expression levels, activated by Toll-like reseptör-4, were higher in bipolar disorder euthymic group, indicated that the inflammatory pathway was active in this group. Tumor necrosis factor-? and interleukin-1ß gene expression levels did not differ significantly between the groups. This finding could be accompanied by the psychotropic drugs which was used to treat bipolar disorder euthymic group. In general, all these findings support that bacterial translocation pathway contributes to the systemic and neuroinflammation in bipolar disorder pathophysiology.
Açıklama
Anahtar Kelimeler
Bipolar Bozukluk, Bakteriyel Translokasyon, Nöroinflamasyon, Stres, Gen Ekspresyonu, Bipolar Disorder, Bacterial Translocation, Neuroinflammation, Stress, Gene Expression
