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Die autokrine Wachstumsregulation sensorischer Neuronen von Gallus gallus
Die autokrine Wachstumsregulation sensorischer Neuronen von Gallus gallus
The tip of a growing axon is known as growth cone. This dynamic structure controls the elongation and steering of neuronal processes. Guidance molecules, which include extracellular purines like adenosine, affect a wide range of neuronal signaling pathways, which often take place in the growth cone. This study is aimed to investigate the effects of stimulation and inhibition of adenosine receptors on the growth of neuronal processes of neurites from sensory neurons. To this end dorsal root ganglia were explanted from chicken embryos and neuronal elongation was further investigated. Here I demonstrate a connection between stimulation and inhibition of the adenosine A2a receptor and the regulation of neurite elongation. Different experiments, with specific agonists and antagonists for all known adenosine receptors (A1, A2a, A2b, A3), show that overall elongation is significantly affected only by A2a selective compounds. Further immune-histochemical data show that A2a receptors are present on the investigated growth cones. Apparently the activation of A2a receptors stimulates neurite elongation whereas the inhibition of this receptor type impedes neurite growth. This finding is supported by experiments with adenosine deaminase, an enzyme which irreversibly deaminates adenosine and acts on neurite elongation like a pharmacological block of A2a receptors. Data of this thesis strongly indicate that adenosine provided by the cells themselves affect neurite elongation. This leads to the question if adenosine or adenine nucleotides are released by sensory neurons from chicken dorsal root ganglia. The release of adenine nucleotides like ATP is more likely than the release of adenosine itself. This hypothesis is firstly based on the presence of quinacrine positive vesicular structures of sensory neurons. Quinacrine is a marker for releasable ATP vesicles. Secondly, the inhibition of ectonucleotidases with ARL 67156 slowed the neurite elongation of sensory neurons. Ectonucleotidases are a family of nucleotide metabolizing enzymes, which break down nucleotides to nucleosides. A recent publication of another group showed that the activation state of the A2a receptor affects neurite growth in primary cortical neurons. This independent study together with the findings of this thesis shows that the A2a receptor activation takes part in the regulation of neuronal elongation. The growth of neuronal processes is the basis of all neuronal connections. There is still a long way to go to fully understand this process. This thesis contributes a small piece of information to a better understanding of the development and regeneration of neuronal systems.
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Werner, Anja Diana
2016
German
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Werner, Anja Diana (2016): Die autokrine Wachstumsregulation sensorischer Neuronen von Gallus gallus. Dissertation, LMU München: Faculty of Biology
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Abstract

The tip of a growing axon is known as growth cone. This dynamic structure controls the elongation and steering of neuronal processes. Guidance molecules, which include extracellular purines like adenosine, affect a wide range of neuronal signaling pathways, which often take place in the growth cone. This study is aimed to investigate the effects of stimulation and inhibition of adenosine receptors on the growth of neuronal processes of neurites from sensory neurons. To this end dorsal root ganglia were explanted from chicken embryos and neuronal elongation was further investigated. Here I demonstrate a connection between stimulation and inhibition of the adenosine A2a receptor and the regulation of neurite elongation. Different experiments, with specific agonists and antagonists for all known adenosine receptors (A1, A2a, A2b, A3), show that overall elongation is significantly affected only by A2a selective compounds. Further immune-histochemical data show that A2a receptors are present on the investigated growth cones. Apparently the activation of A2a receptors stimulates neurite elongation whereas the inhibition of this receptor type impedes neurite growth. This finding is supported by experiments with adenosine deaminase, an enzyme which irreversibly deaminates adenosine and acts on neurite elongation like a pharmacological block of A2a receptors. Data of this thesis strongly indicate that adenosine provided by the cells themselves affect neurite elongation. This leads to the question if adenosine or adenine nucleotides are released by sensory neurons from chicken dorsal root ganglia. The release of adenine nucleotides like ATP is more likely than the release of adenosine itself. This hypothesis is firstly based on the presence of quinacrine positive vesicular structures of sensory neurons. Quinacrine is a marker for releasable ATP vesicles. Secondly, the inhibition of ectonucleotidases with ARL 67156 slowed the neurite elongation of sensory neurons. Ectonucleotidases are a family of nucleotide metabolizing enzymes, which break down nucleotides to nucleosides. A recent publication of another group showed that the activation state of the A2a receptor affects neurite growth in primary cortical neurons. This independent study together with the findings of this thesis shows that the A2a receptor activation takes part in the regulation of neuronal elongation. The growth of neuronal processes is the basis of all neuronal connections. There is still a long way to go to fully understand this process. This thesis contributes a small piece of information to a better understanding of the development and regeneration of neuronal systems.