The midbrain-hindbrain boundary (MHB) is one of the key organizing centers of the vertebrate central nervous system (CNS). Its patterning is governed by a well-described gene regulatory network (GRN) involving several transcription factors, namely, pax, gbx, en, and otx, together with signaling molecules of the Wnt and Fgf families. Here, we describe the onset of these markers in Oryzias latipes (medaka) early brain development in comparison to previously known zebrafish expression patterns. Moreover, we show for the first time that vox, a member of the vent gene family, is expressed in the developing neural tube similarly to CNS markers. Overexpression of vox leads to profound changes in the gene expression patterns of individual components of MHB-specific GRN, most notably of fgf8, a crucial organizer molecule of MHB. Our data suggest that genes from the vent family, in addition to their crucial role in body axis formation, may play a role in regionalization of vertebrate CNS.

• Klíčová slova
• Gene regulatory network, Heat shock element, Midbrain-hindbrain boundary, fgf8, medaka, vox,
• MeSH
• embryo nesavčí metabolismus   MeSH
• genové regulační sítě MeSH
• homeodoménové proteiny genetika   metabolismus   MeSH
• mezencefalon embryologie   metabolismus   MeSH
• Oryzias embryologie   genetika   MeSH
• rombencefalon embryologie   metabolismus   MeSH
• rybí proteiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• homeodoménové proteiny MeSH
• rybí proteiny MeSH

OBJECTIVES: In our previous studies we found that both acute administration of CB1 receptor agonist methanandamide and repeated methanandamide pre-treatment prior to methamphetamine challenge dose elicited increase in the CB1 receptor mRNA expression in the mouse mesencephalon. As a reciprocal cross-talk is reported between the cannabinoid CB1 and dopamine receptors, that are highly co-localized on brain neurones, we targeted possible changes in relative expression of dopamine D1 and D2 receptor mRNA in mesencephalon in mice sensitized by repeated treatments to methamphetamine stimulatory effects and cross-sensitized to methamphetamine by cannabinoid CB1 receptor agonist methanandamide pre-treatment. METHODS: To confirm development of behavioural sensitization or cross-sensitization, respectively, we observed changes in locomotion using the open field test. Mice were treated repeatedly with either methamphetamine or methamphetamine after repeated pre-treatment with methanandamide. After each measurement of locomotion one third of animals were sacrificed and the brain was stored. RNA was isolated from the midbrain and used for reverse transcription and subsequent real-time PCR. RESULTS AND CONCLUSION: As in many of our earlier studies with the same dosage regimen we found in the behavioural part both development of sensitization to methamphetamine stimulatory effects after repeated treatment and cross-sensitization to them by pre-treatment with cannabinoid receptor CB1 agonist methanandamide. Real-time PCR analyses showed an increase in D1 receptor mRNA expression after the first dose of methamphetamine (that persisted also after the last dose of methamphetamine) and after the first dose of methanandamide (which also persisted after the methamphetamine challenge dose). In opposite a significant decrease in D2 receptor mRNA expression both after the first dose of methamphetamine and methanandamide (that persisted also after the methamphetamine challenge doses) was registered. Thus, our results suggest that both methamphetmine and methanandamide treatment can provoke changes in dopamine receptor density in mouse mesenpcephalon, the increase in D1 and decrease in D2 receptor subtypes.

• MeSH
• chování zvířat účinky léků   MeSH
• dopaminové látky farmakologie   MeSH
• interakce mezi receptory a ligandy účinky léků   MeSH
• kyseliny arachidonové farmakologie   MeSH
• lékové interakce MeSH
• messenger RNA analýza   MeSH
• methamfetamin farmakologie   MeSH
• mezencefalon účinky léků   metabolismus   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• náhodné rozdělení MeSH
• pohybová aktivita účinky léků   MeSH
• receptor kanabinoidní CB1 agonisté   MeSH
• receptory dopaminu D1 účinky léků   genetika   metabolismus   MeSH
• receptory dopaminu D2 účinky léků   genetika   metabolismus   MeSH
• rozvrh dávkování léků MeSH
• senzibilizace centrálního nervového systému účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dopaminové látky MeSH
• kyseliny arachidonové MeSH
• messenger RNA MeSH
• methamfetamin MeSH
• methanandamide MeSH Prohlížeč
• receptor kanabinoidní CB1 MeSH
• receptory dopaminu D1 MeSH
• receptory dopaminu D2 MeSH

OBJECTIVES: Since among others also our previous studies suggested an interaction between the endocannabinoid system and methamphetamine brain mechanisms we focused on possible changes in relative expression of cannabinoid CB1 receptor mRNA in mesencephalon from mice sensitized by repeated treatments to methamphetamine stimulatory effects and cross-sensitized by cannabinoid CB1 receptor agonist methanandamide pre-treatment. METHODS: The Open Field Test was used to measure changes in terms of behavioural sensitization or cross-sensitization to drug effects on locomotion in male mice treated repeatedly with either methamphetamine or methamphetamine after pre-treatment with methanandamide. After each measurement one third of animals were sacrificed and the brain was stored. RNA was isolated from the midbrain and used for reverse transcription and subsequent real-time PCR. RESULTS AND CONCLUSION: The evaluation of behavioural drug effects showed both development of sensitization to methamphetamine stimulatory effects after repeated treatment and cross-sensitization to them by pre-treatment with cannabinoid receptor CB1 agonist methanandamide. Real-time PCR analyses revealed an increase in CB1 receptor mRNA expression after the first dose of methanandamide followed by decrease after the combined treatment with methamphetamine challenge dose. Our findings suggest that particularly repeated pre-treatment with CB1 agonist methanandamide can elicit increase in the mRNA expression level at least in the mouse mesencephalon neurons associated with cross-sensitization to methamphetamine stimulatory effects.

• MeSH
• adrenergní látky farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• kyseliny arachidonové farmakologie   MeSH
• lokomoce účinky léků   MeSH
• messenger RNA metabolismus   MeSH
• methamfetamin farmakologie   MeSH
• mezencefalon cytologie   účinky léků   metabolismus   MeSH
• myši MeSH
• náhodné rozdělení MeSH
• neurony účinky léků   metabolismus   MeSH
• receptor kanabinoidní CB1 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adrenergní látky MeSH
• kyseliny arachidonové MeSH
• messenger RNA MeSH
• methamfetamin MeSH
• methanandamide MeSH Prohlížeč
• receptor kanabinoidní CB1 MeSH

The aim of the present study was to determine hypoxia-induced changes in the long-term expression of tyrosine hydroxylase (TH) mRNA and the steady-state dopamine (DA) levels in rat mesencephalic cell cultures. The cultures were exposed to hypoxia during the early developmental period, and DA content and TH mRNA expression were determined on day in vitro (DIV) 14. Hypoxic exposure of 5-day-old cultures resulted in increased DA (control 89.9+/-8.9, hypoxia 135.8+/-23.7 pg/microg protein) and TH mRNA (control 37.3+/-4.7, hypoxia 143.1+/-49.4 pg/microg RNA) levels. To analyze the involvement of hypoxia-inducible factor-1 (HIF-1) in these changes, we studied its activation using reporter gene. Hypoxia caused a 3-fold increase in HIF-1 activity. Our data suggest that hypoxia/ischemia during the putative critical developmental period of neurons may determine the tyrosine hydroxylase gene expression and, consequently, the development of the dopaminergic system.

• MeSH
• DNA vazebné proteiny metabolismus   MeSH
• dopamin genetika   metabolismus   MeSH
• exprese genu MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• faktor 1 indukovatelný hypoxií MeSH
• hypoxie metabolismus   MeSH
• jaderné proteiny metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• messenger RNA metabolismus   MeSH
• mezencefalon metabolismus   MeSH
• potkani Wistar MeSH
• transkripční faktory metabolismus   MeSH
• tyrosin-3-monooxygenasa genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• dopamin MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• faktor 1 indukovatelný hypoxií MeSH
• Hif1a protein, rat MeSH Prohlížeč
• jaderné proteiny MeSH
• messenger RNA MeSH
• transkripční faktory MeSH
• tyrosin-3-monooxygenasa MeSH

A great variety of alterations have been described in the nervous system of diabetic animals. They are named as diabetic neuropathy and affect the brain, spinal cord and peripheral nerves. In diabetic animals, plasma and tissue catecholamine levels have been reported to be increased, decreased or unchanged, and these disparities have been explained by differences in the tissues selected, severity or duration of diabetes. Dopamine, norepinephrine and epinephrine from different tissues were extracted by absorption onto alumina, and measured by high performance liquid chromatography with electrochemical detection. We found that diabetes alters catecholaminergic systems in a highly specific manner. The dopamine content is reduced in the dopaminergic nigrostriatal system only. Norepinephrine is differently altered in several areas of the sympathetic nervous system. It is increased in cardiac ventricles, and decreased in stellate ganglia and the blood serum. However, it is not altered in the central nervous system. Finally, epinephrine is only altered in the adrenal gland where it is increased, and in the serum where it is reduced. Our results suggest that diabetes reduces the activity of the nigrostriatal dopaminergic system. Changes found at the sympathoadrenal level could be explained by reduced norepinephrine and epinephrine synthesis, with increased storage due to a reduced release from synaptic vesicles.

• MeSH
• adrenalin krev   metabolismus   MeSH
• bazální ganglia chemie   metabolismus   MeSH
• centrální nervový systém metabolismus   MeSH
• diabetické neuropatie komplikace   metabolismus   MeSH
• dopamin krev   metabolismus   MeSH
• experimentální diabetes mellitus komplikace   metabolismus   patofyziologie   MeSH
• ganglion stellatum chemie   metabolismus   MeSH
• katecholaminy krev   metabolismus   MeSH
• krevní glukóza analýza   MeSH
• krysa rodu Rattus MeSH
• medulla oblongata chemie   metabolismus   MeSH
• mezencefalon chemie   metabolismus   MeSH
• nadledviny chemie   metabolismus   MeSH
• noradrenalin krev   metabolismus   MeSH
• periferní nervový systém metabolismus   MeSH
• pons chemie   metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• srdeční komory chemie   metabolismus   MeSH
• sympatický nervový systém metabolismus   MeSH
• tělesná hmotnost MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adrenalin MeSH
• dopamin MeSH
• katecholaminy MeSH
• krevní glukóza MeSH
• noradrenalin MeSH

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• atropin farmakologie   MeSH
• diencefalon metabolismus   MeSH
• mezencefalon metabolismus   MeSH
• mozek účinky léků   enzymologie   metabolismus   MeSH
• myši MeSH
• pyridinové sloučeniny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• atropin MeSH
• pyridinové sloučeniny MeSH

• MeSH
• bazální ganglia metabolismus   MeSH
• krysa rodu Rattus MeSH
• mezencefalon metabolismus   MeSH
• mozková kůra metabolismus   MeSH
• růst MeSH
• spotřeba kyslíku * MeSH
• štítná žláza fyziologie   MeSH
• terapeutická hypotermie MeSH
• tyreoidektomie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH