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The function of GABA and its B-receptor in Schwann cell development
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancer och vaskulärbiologi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
Syddansk Universitet, IMM-Neurobiology Reseach, Denmark .
Visa övriga samt affilieringar
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nyckelord [en]
GABA, GABA(B) receptor, GAD, Schwann cell, nonmyelinating Schwann cell, satellite cell, baclofen, CGP55485
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
Neurovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-157967OAI: oai:DiVA.org:uu-157967DiVA, id: diva2:437253
Tillgänglig från: 2011-08-28 Skapad: 2011-08-28 Senast uppdaterad: 2018-01-12
Ingår i avhandling
1. Neuron-glial Interaction in the Developing Peripheral Nervous System
Öppna denna publikation i ny flik eller fönster >>Neuron-glial Interaction in the Developing Peripheral Nervous System
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The nervous system, including the brain, is the most sophisticated organ in the mammalian body. In such a complex network, neuron-glial interaction is essential and controls most developmental processes, such as stem cell fate determination, migration, differentiation, synapse formation, ensheathment and myelination. Many of these events are critical for the developmental process and small errors can lead to growth retardation, malformation or disease. The understanding of the normal progress of nervous system development is fundamental and will help the discovery of new treatments for disease.

This thesis discusses three types of neuron-glia interactions at different developmental stages; neural stem/progenitor cell (NSPC) differentiation, building and maintaining the structure of the sciatic nerve, and myelin formation.

In Paper I we show that NSPCs, based upon their morphology and expression of specific protein markers, have the capacity to differentiate into cells of either the peripheral nervous system (PNS) or enteric nervous system (ENS) when grown with PNS or ENS primary cell cultures, or fed with conditioned medium from these. This indicates that soluble factors secreted from the PNS or ENS cultures are important for stem cell differentiation and fate determination.

The adhesion protein neuronal cadherin (N-cadherin) is implicated in migration, differentiation and nerve outgrowth in the developing PNS. In Paper II N-cadherin was exclusively found in ensheathing glia (nonmyelinating Schwann cells, satellite cells and enteric glia) in contact with each other or with axons. Functional blocking of N-cadherin in dissociated fetal dorsal root ganglia (DRG) cultures led to a decrease in attachment between Schwann cells. N-cadherin-mediated adhesion of nonmyelinating Schwann cells may be important in encapsulating thin calibre axons and provide support to myelinating Schwann cells.

In Paper III the inhibitory gamma aminobutyric acid (GABA) and GABAB receptors were studied in the Schwann cell of the adult sciatic nerve and DRG cultures. GABAB receptors were primarily expressed in nonmyelinating Schwann cells and protein levels decreased during development and myelination. Blocking the GABAB receptor in long-term DRG cultures led to decreased levels of mRNA markers for myelin. These results indicate that the GABA and GABAB receptors may be involved in Schwann cell myelination.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2011. s. 63
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 697
Nyckelord
Schwann cell, nonmyelinating Schwann cell, myelinating Schwann cell, development, proliferation, differentiation, myelin, neural stem cell, central nervous system, peripheral nervous system, enteric nervous system, N-cadherin, GABA, GAD, GABA(B) receptor, baclofen, CGP55485
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
Neurovetenskap
Identifikatorer
urn:nbn:se:uu:diva-157968 (URN)978-91-554-8142-1 (ISBN)
Disputation
2011-10-14, B22, BMC, Husargatan 3, Uppsala, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2011-09-22 Skapad: 2011-08-28 Senast uppdaterad: 2018-01-12Bibliografiskt granskad

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Corell, Mikael

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