| 1. |
- Andersson, Daniel, et al.
(author)
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Partial depletion of dopamine in substantia nigra impairs motor performance without altering striatal dopamine neurotransmission
- 2006
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 24:2, s. 617-624
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Journal article (peer-reviewed)abstract
- Previous data indicate that the release of somatodendritic dopamine in substantia nigra influences motor activity and coordination, but the relative importance of somatodendritic dopamine release vs. terminal striatal dopamine release remains to be determined. We utilized simultaneous measurement of dopamine neurotransmission by microdialysis and motor performance assessment by rotarod test to investigate the effects of local dopamine depletion in rats. The vesicular monoamine transporter inhibitor tetrabenazine (100 µm) was administered locally in substantia nigra as well as in striatum. Nigral tetrabenazine administration decreased nigral dopamine dialysate concentrations to 7% of baseline and whole-tissue dopamine content by 60%. Nigral dopamine depletion was associated with a reduction in motor performance to 73 ± 6% of pretreatment value, but did not alter dialysate dopamine concentrations in the ipsilateral striatum. Striatal tetrabenazine administration decreased striatal dopamine dialysate concentrations to 5% of baseline and doubled the somatodendritic dopamine response to motor activity, but it was not associated with changes in motor performance or dopamine content in striatal tissue. Simultaneous treatment of substantia nigra and striatum reduced motor performance to 58 ± 5% of the pretreatment value. The results of this study indicate that partial depletion of nigral dopamine stores can significantly impair motor functions, and that increased nigral dopamine release can counteract minor impairments of striatal dopamine transmission.
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| 2. |
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| 3. |
- Bergquist, Filip, 1970, et al.
(author)
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Neuropeptide release
- 2008
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In: Encyclopedia of Neuroscience. - Oxford : Academic Press. - 9780080450469
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Book chapter (other academic/artistic)abstract
- Neuropeptides are by far the largest class of chemical signals used by the central and peripheral nervous system. They are released from large dense core vesicles and here we compare the mechanisms of neuropeptide release with the mechanisms of classical transmitter release from small synaptic vesicles.
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| 4. |
- Bergquist, Filip, 1970, et al.
(author)
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Role of the commissural inhibitory system in vestibular compensation in the rat.
- 2008
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In: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 586:Pt 18, s. 4441-52
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Journal article (peer-reviewed)abstract
- We investigated the role of the vestibular commissural inhibitory system in vestibular compensation (VC, the behavioural recovery that follows unilateral vestibular loss), using in vivo microdialysis to measure GABA levels in the bilateral medial vestibular nucleus (MVN) at various times after unilateral labyrinthectomy (UL). Immediately after UL, in close correlation with the appearance of the characteristic oculomotor and postural symptoms, there is a marked increase in GABA release in the ipsi-lesional MVN. This is not prevented by bilateral flocculectomy, indicating that it is due to hyperactivity of vestibular commissural inhibitory neurones. Over the following 96 h, as VC occurs and the behavioural symptoms ameliorate, the ipsi-lesional GABA levels return to near-normal. Contra-lesional GABA levels do not change significantly in the initial stages of VC, but decrease at late stages so that when static symptoms have abated there remains a significant difference between the MVNs of the two sides. We also investigated the role of the commissural inhibition in Bechterew's phenomenon, by reversibly inactivating the intact contra-lesional labyrinth in compensating animals through superfusion of local anaesthetic on the round window. Transient inactivation of the intact labyrinth elicited the lateralized behaviour described by Bechterew, but did not alter the GABA levels in either MVN, suggesting the involvement of distinct cellular mechanisms. These findings indicate that an imbalanced commissural inhibitory system is a root cause of the severe oculomotor and postural symptoms of unilateral vestibular loss, and that re-balancing of commissural inhibition occurs in parallel with the subsequent behavioural recovery during VC.
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| 5. |
- Brederlau, Anke, 1968, et al.
(author)
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Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease: effect of in vitro differentiation on graft survival and teratoma formation.
- 2006
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In: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 24:6, s. 1433-40
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Journal article (peer-reviewed)abstract
- Human embryonic stem cells (hESCs) have been proposed as a source of dopamine (DA) neurons for transplantation in Parkinson's disease (PD). We have investigated the effect of in vitro predifferentiation on in vivo survival and differentiation of hESCs implanted into the 6-OHDA (6-hydroxydopamine)-lesion rat model of PD. The hESCs were cocultured with PA6 cells for 16, 20, or 23 days, leading to the in vitro differentiation into DA neurons. Grafted hESC-derived cells survived well and expressed neuronal markers. However, very few exhibited a DA neuron phenotype. Reversal of lesion-induced motor deficits was not observed. Rats grafted with hESCs predifferentiated in vitro for 16 days developed severe teratomas, whereas most rats grafted with hESCs predifferentiated for 20 and 23 days remained healthy until the end of the experiment. This indicates that prolonged in vitro differentiation of hESCs is essential for preventing formation of teratomas.
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| 6. |
- Olabi, Bayanne, et al.
(author)
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Rebalancing the commissural system: mechanisms of vestibular compensation.
- 2009
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In: Journal of vestibular research : equilibrium & orientation. - 1878-6464. ; 19:5-6, s. 201-7
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Research review (peer-reviewed)abstract
- Vestibular compensation after unilateral vestibular loss is a complex, multi-factored process involving synaptic and neuronal plasticity in many areas of the brain, and it is a challenge to identify the key sites of plasticity that determine the rate and extent of behavioural recovery. Experimental evidence strongly implicates the vestibular commissural inhibitory system which links the brainstem vestibular nuclei of the two sides, both in causing the initial severe oculomotor and postural symptoms of vestibular deafferentation, and in the subsequent recovery that takes place in the early stages of compensation. Of particular interest are changes in GABAergic neurotransmission within the commissural system, and the possibility that histaminergic drugs as well as stress steroids and neurosteroids that can modulate compensation, may do so at least in part by their effects on commissural inhibition. A fuller understanding of the role of the commissural system in compensation and the effects of GABAergic neuromodulators is likely to reveal the mechanisms of action of histamine in the vestibular system and the interactions between stress, anxiety and vestibular dysfunction.
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