Modulation of the glial response via the platelet-derived growth factor receptors (PDGFR) on the diencephalic dopaminergic neurons in zebrafish larvae

Abstract

s / Parkinsonism and Related Disorders 22 (2016) e149ee192 e180 P 6.017. MODULATION OF THE GLIAL RESPONSE VIA THE PLATELET-DERIVED GROWTH FACTOR RECEPTORS (PDGFR) ON THE DIENCEPHALIC DOPAMINERGIC NEURONS IN ZEBRAFISH LARVAE Anwar Norazit, David Wong, Nadia Abdul Halim, Suzita Mohd Noor. Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Objectives: Activated astrocytes express PDGF receptors on their surface. PDGF may have a role in modulating the expression of astrocytes to act as neuroprotectors on the dopaminergic neurons. Methods: Zebrafish larvae were treated with either 0.1% DMSO (vehicle control), Imatinib (PDGFR inhibitor), 0.1 mg/ml MPTP (dopaminergic neurotoxin), or a combination of Imatinib and MPTP at 4 dpf. Solutions were refreshed daily and larvae were maintained till 7 dpf. Behavioural analyses was conducted to measure response to tail touch and posture before and after tail touch. The presence of spinal curvature was also observed. RT-PCR was done to determine the expression levels of th (dopaminergic neurons) and gfap (astrocytes). Results: Behaviour analyses revealed marked slow responses in larvae treated with MPTP, Imatinib and Imatinib in combination with MPTP. Furthermore, a significant (p<0.05) number of Imatinib-treated larvae and larvae treated in combination with Imatinib and MPTP exhibited spinal curvatures compared to other treatment groups. Despite the behavioural changes, gene expression analysis did not show any qualitative change for all treated groups. Conclusion: These findings suggest PDGF may have a role in modulating astrocytes' neuroprotective response via the PDGF receptors. The changes in behavioural indices needs to be confirmed by qRT-PCR and wholemount in situ immunofluorescence. P 6.018. INTEGRATION OF CORTICAL AND BASAL GANGLIA INPUTS IN MOTOR THALAMUS OF PARKINSONIAN ANIMAL MODELS Gerg Orban, Wei Song, Alain Kaelin-Lang, Salvatore Galati. Neurocenter of Southern Switzerland, Lugano, Switzerland Objectives: Pathological erratic motor thalamus (MTh) activity has been considered to contribute to the generation of Parkinson's disease (PD) symptoms. Basal ganglia (BG) structures afferent to MTh shown synchronized oscillatory activity in dopamine (DA) -depleted BG reflecting underlying pathophysiological mechanisms of Parkinsonism. Acute or chronic DA depletion, drives pathological cortical-substantia nigra pars reticulata (SNr) coherences in urethane-anesthetized rats. Since SNr exerts direct control on the BG-receiving MTh relaying information to the cortex, its disorganized patterns of activity may have a strong influence on the activity of the downstream thalamocortical relay. We aim to characterized the impact of these changes on MTh. Methods: We investigate the firing properties of MTh cells following i) chronic DA depletion in 6-hydroxydopamine (6-OHDA) animal models of PD and ii) in acute DA depleted animals after tetrodotoxin (TTX)-mediated blockade of the nigro-striatal pathway. Results: MTh neurons showed a firing reduction in 6-OHDA animals. In TTX group we observed a time-looked inhibition of MTh cells (Figure1). Conclusions: The MTh is a structure strategically situated between BG and cortex whose activity was conjectured to play a crucial role in PD. Our preliminary data are in agreement with the classical basal ganglia scheme. P 6.019. SPREADING DEPRESSION SUSCEPTIBILITY IS REDUCED IN PARKINSON RAT MODEL Mahmoud Lotfinia. Shefa Neuroscience Research Center, Tehran, Islamic Republic of Iran Objectives: To evaluate whether administration of 6-hydroxydopamine in the medial forebrain bundle and creating a Parkinson rat model, can have an effect on Spreading depression Susceptibility or not? Parkinson disease (PD) is known by amajor loss of dopaminergic nigrostriatal neurons and by an increased turnover of neurotransmitter by surviving neurons of the nigrostriatal tract. The clinical diagnosis of PD is based on the identification of some combination of the cardinal motor signs of bradykinesia, rigidity, tremor, and postural instability. Spreading depression (SD) known as an evoked neuronal activity and changes in ionic, metabolic and hemodynamic characteristics of the brain. Pronounced release of dopamine during SD and the probable role of dopamine in SD process suggests that disruption of dopaminergic pathway in PD may cause SD to behave differently. Methods: To test this possibility, we induced dopaminergic lesion by bilateral intracerebral stereotactic injection of 6 mL of 6-hydroxydopamine in the medial forebrain bundle (MFB). After 4 days, SD was induced by the injection of 3M KCl and SD propagation was followed using two ion-sensitive microelectrodes placed in the parietal and occipital cortex. Results: Eliciting SD in ratmodel was associatedwith a significant increase in the threshold of SD and a decrease in the propagation velocity and duration of accompanying extracellular DC changes. Conclusions: The present data show that rat model of Parkinson's disease are less prone to SD.