The identification, enrichment and subsequent isolation of spermatogonial stem cells (SSCs) are integral to the success of SCC transplants between fertile donor and sterilized recipient males. In birds generally and particularly in chicken, SSC-specific has yet to be identified. The receptor for glial cell-derived neurotrophic factor (GDNF), i.e. GDNF family receptor alpha-1 (GFRα1), has been identified as a potential marker for different mouse spermatogonial subtypes. In the present study, we characterized the chicken cGFRα1 receptor and compared its predicted amino-acid sequence with mouse, rat and human GFRα1 proteins. Using specific polyclonal mouse anti-cGFRα1 serum, a total of 2.8% cells were recognized as cGFRα1-positive among isolated testicular cells recovered from sexually mature cockerels. The percentages of cGFRα1-positive testicular cells with haploid, diploid, tetraploid and SP DNA content were 1.6%, 2.5%, 39.3% and 76.8%, respectively. The presence of cGFRα1 protein on the surfaces of all cells of the seminiferous epithelium was confirmed by immunocytochemical and immunohistochemical analyses. Tissue specificity of cGFRα1 mRNA expression was significantly higher in adult testes compared to brain tissue which itself was several times higher than tissues prepared from the spleen, liver and heart. No expression was observed in muscular tissue. At last, we demonstrated the successful repopulation of sterilized recipient's testes with transplanted cGFRα1-positive donor testicular cells. Recipient males subsequently produced functional heterologous spermatozoa capable of fertilizing an ovum and obtaining chicks with donor cell genotypes.

• MeSH
• biologické markery MeSH
• dospělé kmenové buňky fyziologie   MeSH
• genotyp MeSH
• klonování DNA MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• molekulární sekvence - údaje MeSH
• protilátky krev   MeSH
• receptory GDNF genetika   metabolismus   MeSH
• regulace genové exprese fyziologie   MeSH
• sekvence aminokyselin MeSH
• testis cytologie   MeSH
• transplantace kmenových buněk veterinární   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hereditary cerebellar degenerations are severe and complex diseases for which there is currently no effective causal treatment. A hopeful method could be the support of plasticity or neurotransplantation. However, there are still many unknown aspects which could influence the outcome of treatment. As neurotrophic factors are essential in neuroplasticity and neuronal integration, potential abnormalities in their levels could be involved in the pathogenesis of the disease and would possibly explain the unsuitability of diseased cerebellum for the graft integration. The aim of this study was to identify and compare basal levels of trophic factors BDNF and GDNF in the cerebellum in two mouse models of cerebellar degeneration - Lurcher and pcd. Basal levels of BDNF in the cerebellum have been shown to be lower in both mutant models than in healthy controls. However, the GDNF levels were surprisingly increased in the cerebella of Lurcher mutant mice compared to both wild type and pcd mice. In addition, a different distribution of GFAP-positive cells in the cerebellum was revealed in Lurcher mice. These differences suggest that the niche of the Lurcher mutant cerebellum is changed. The question, however, remains how these changes are related to the neurodegenerative process and how they could influence potential compensatory mechanisms, plasticity and response to therapeutic interventions.

• MeSH
• biologické markery metabolismus   MeSH
• mozeček chemie   metabolismus   MeSH
• mozkový neurotrofický faktor genetika   metabolismus   MeSH
• mutace fyziologie   MeSH
• myši - mutanty neurologické MeSH
• myši inbrední CBA MeSH
• myši transgenní MeSH
• myši MeSH
• neurodegenerativní nemoci genetika   metabolismus   MeSH
• růstový faktor GDNF genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Neurotrophins, especially brain-derived neurotrophic factor (BDNF) have gained significant therapeutic interest particularly in neurologic and psychiatric disorders and they have been found in human breast milk of mothers who suffered from adverse outcomes in pregnancy. This study tested the hypothesis that oral administration of BDNF/GDNF (glial cell line-derived neurotrophic factor) can exert a biological effect in a rat model of severe neuropathology induced by olfactory bulbectomy (OBX), which exhibits dysregulation of BDNF signaling and impaired blood-brain barrier. METHODS: Adult male albino Sprague-Dawley rats underwent the OBX surgery and separate groups of OBX and sham-operated controls received one oral dose of vehicle, BDNF (0.005 mg/kg), GDNF (0.03 mg/kg) or their combination. One week after neurotrophin dosing the rats were sacrificed and BDNF level was assessed by ELISA in the blood serum and cerebrospinal fluid. RESULTS: A significant decrease of serum BDNF level was found in the OBX model. This alteration was normalized by all types of treatment BDNF, GDNF, or their combination. No influence of sham surgery or treatment was observed in the control rats. BDNF levels in cerebrospinal fluid were below detection limit. CONCLUSION: This study indicates that oral administration of neurotrophins is able to exert a biological effect in the OBX model. There is a number of potential mechanisms, which remain to be elucidated.

• MeSH
• aplikace orální MeSH
• biologický transport MeSH
• bulbus olfactorius chirurgie   MeSH
• hematoencefalická bariéra účinky léků   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• mozkový neurotrofický faktor aplikace a dávkování   krev   mozkomíšní mok   MeSH
• nemoci mozku krev   MeSH
• neurotrofní faktory aplikace a dávkování   krev   mozkomíšní mok   MeSH
• ověření koncepční studie MeSH
• potkani Sprague-Dawley MeSH
• rekombinantní proteiny MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• neurony fyziologie   MeSH
• rodina proteinů GDNF fyziologie   MeSH

• MeSH
• B-lymfocyty MeSH
• buněčná imunita MeSH
• imunologické techniky MeSH
• neurotrofní faktory MeSH
• receptory faktorů růstu nervů MeSH
• T-lymfocyty MeSH
• Publikační typ
• vysokoškolské kvalifikační práce MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biologie
• neurovědy
• biochemie

Mr. Beal is an activist and writer who cofounded and directs the harm reduction organization Cures-Not-Wars. He has long been an advocate of ibogaine, a naturally occurring plant alkaloid that is used to treat substance dependence. Mr. Beal has present- ed on ibogaine in numerous conferences and his published work has appeared in the peer reviewed scientific literature and includes the book the Ibogaine Story, which is cited by Alexander Shulgin as one of four definitive source works on ibogaine. Mr. Beal’s activism was a critical influence in the decision of the National Institute on Drug Abuse to study ibogaine in the early 1990s, and has produced numerous articles on ibogaine in the mainstream media, as well as major support for the International Conference on Ibogaine held at New York University in 1999. He was the first to lend organized support for the development of ibogaine in 1980.

• Publikační typ
• abstrakty MeSH

BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0). INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.

• MeSH
• bipolární porucha farmakoterapie   genetika   MeSH
• celogenomová asociační studie MeSH
• fenotyp MeSH
• genetická variace MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• receptory GDNF genetika   MeSH
• sloučeniny lithia terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

• MeSH
• biochemie MeSH
• exony MeSH
• genetika MeSH
• molekulární biologie MeSH
• molekulární sekvence - údaje MeSH
• Publikační typ
• vysokoškolské kvalifikační práce MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• genetika, lékařská genetika
• biologie
• biochemie

Úvod a cíl: Nový typ koronaviru (COVID-19) způsobuje vysokou horečku, únavu, kašel, dechové potíže, průjmy, u některých pacientů bolesti hlavy, cerebrovaskulární onemocnění, bezvědomí, encefalopatii, encefalitidu, poškození periferního nervového systému atd. Jedná se o virové respirační onemocnění, které se projevuje neurologickými nálezy. V naší studii byly zkoumány hladiny neurotrofického faktoru odvozeného od glií (glial-derived neurotrophic factor; GDNF) a nervového růstového faktoru (nerve growth factor; NGF) neurotrofických faktorů (NF), které zajišťují přežití, růst, zrání a diferenciaci neuronů u pacientů s COVID-19 a jejich vztah se závažností onemocnění. Materiál a metody: Z celkového počtu 70 účastníků je 20 účastníků ve zdravé kontrolní skupině (CG) a 50 účastníků je ve skupině pacientů s COVID-19 dle PCR testu (nekomplikovaná skupina [NCG], středně těžká skupina [MG], těžká skupina [SG]). Hladiny NGF a GDNF v séru ve všech skupinách byly hodnoceny spektrofotometricky pomocí metody ELISA. Výsledky byly porovnány jak mezi skupinami pacientů, tak mezi pacienty a kontrolní (zdravou) skupinou. Výsledky: Koncentrace NGF v séru byla signifikantně vyšší ve skupině MG než ve skupinách NCG a SG (p = 0,042). U sérových hladin GDNF u pacientů s COVID-19 a CG nebyly zjištěny statisticky významné rozdíly. Závěr: Nebyl zjištěn žádný rozdíl v sérových hladinách NGF a sérových hladinách GDNF u pacientů s onemocněním COVID-19 ve srovnání se zdravou kontrolní skupinou.

Introduction and objective: The new type of coronavirus (COVID-19) causes high fever, fatigue, cough, respiratory distress, diarrhea, headache in some patients, cerebrovascular diseases, unconsciousness, encephalopathy, encephalitis, peripheral nervous system damage, etc. It is a viral respiratory disease that manifests itself with neurological findings. In our study, glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) levels of neurotrophic factors (NF), which ensure the survival, growth, maturation and differentiation of neurons were investigated in COVID-19 patients, including their relationship with the severity of the disease. Materials and methods: Out of a total of 70 participants, 20 participants are in the healthy control group (CG) and 50 participants are in the group of patients with COVID-19 according to PCR test (uncomplicated group [NCG], moderately severe group [MG], severe group [SG]). Serum NGF and GDNF levels in all groups were evaluated spectrophotometrically using ELISA kits. The results were compared both between the patient groups and between the patient and healthy control groups. Results: Serum NGF concentration was significantly higher in the MG group than in the NCG and the SG group (P = 0.042). No statistically significant difference was found in serum GDNF levels in COVID-19 patients and CG. Conclusion: There was no difference in serum NGF and serum GDNF levels in COVID-19 patients compared to the healthy control group.

• Klíčová slova
• neurotrofický faktor odvozený od gliových buněk,
• MeSH
• COVID-19 * patofyziologie   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• nervový růstový faktor analýza   MeSH
• Check Tag
• lidé MeSH

Hirschsprungova choroba (HSCR) je vrozené vývojové onemocnění enterického nervového systému. Příčinou je chybějící intramurální inervace určitého úseku střeva. Postižený střevní úsek je trvale stažen a zdravé střevo nad ním se postupně dilatuje a vytváří megakolon. Rozlišuje se několik variant HSCR podle délky postiženého úseku střeva. HSCR se vyskytuje izolovaně nebo syndromicky, sporadicky (80 %) nebo familiárně (20 %). Genetická podstata HSCR je komplexní, je známo 12 příčinných genů zapojených v různých signalizačních kaskádách. Majoritním genem je RET proto-onkogen, kde se nalézají příčinné inaktivující mutace nebo predispoziční varianty v kódující i nekódující části genu. Dalšími geny jsou geny zapojené do RET/GDNF kaskády nebo EDNRB/ENT3 kaskády a s nimi spojené transkripční faktory modulující aktivitu těchto drah. Tyto dráhy a faktory spolu souvisejí a vzájemně se ovlivňují. Kromě příčinných genů je známa řada modifikujících genů, které mohou ovlivňovat fenotyp HSCR. Poznáním genetické podstaty HSCR je možné odhalit příčinu vzniku HSCR, zjistit dědičnost a penetranci jednotlivých mutací. Protože RET proto-onkogen je také příčinou vzniku medulárního karcinomu štítné žlázy (MTC), jsou pacienti s HSCR ve zvýšeném riziku MTC a všichni pacienti by měli být doporučeni ke genetickému screeningu.

Hirschsprung´s disease (HSCR) is a congenital developmental disease of enteric nervous system. The cause is the congenital primary loss of intramural innervation of certain bowel segment. The affected part of bowel is permanently contracted and the healthy bowel above is dilatated and it leads to the development of megacolon. Several variants of HSCR are distinguished by different length of affected colon. It is occurred alone or syndromic, sporadic (80%) or familial form (20%) of HSCR. Genetic cause of HSCR is complex, 12 causative genes are known to be involved in different signal cascades. The major gene is the RET proto-oncogene, where causative inactivating mutations or predisposing variants in coding or non-coding part of gene are found. The other genes are involved in RET/GDNF or EDNRB/ENT3 cascades and transcription factors modulating activities of these cascades. These cascades and factors are in connection and influence themselves. Beside causative genes several modifying genes are known that can influence phenotype of HSCR. Due to the recognition of genetic cause of HSCR it is possible to find the cause of development of HSCR, distinguish the inheritance and the penetrance of each mutation. Because mutations in the RET proto-oncogene are known to be the cause of development of medullary thyroid carcinoma (MTC), patients with HSCR are in higher risk of MTC and all patients should be recommended to genetic screening.

• MeSH
• chromozomální aberace MeSH
• endotelin-3 genetika   MeSH
• fenotyp MeSH
• fyziologie buňky MeSH
• genetické nemoci vrozené MeSH
• genetické testování MeSH
• haplotypy MeSH
• Hirschsprungova nemoc * genetika   MeSH
• lidé MeSH
• medulární karcinom MeSH
• mutace MeSH
• nádory štítné žlázy MeSH
• protoonkogeny MeSH
• signální transdukce MeSH
• transkripční faktory SOXE MeSH
• transkripční faktory MeSH
• zinkové prsty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH