Phase validation of neurotoxic animal models of Parkinson's disease

Telkes, İlknur
Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic nigral neurons and striatal dopamine resulting in serious motor deficits but also some non-motor anomalies. Animal models of human neurodegenerative diseases are essential for better understanding their pathogenesis and developing efficient therapeutic tools. There are many different PD models, however, none of them is fully reproducing all the symptoms of the disease. In addition, different investigators use different behavioral measures which makes even more difficult to compare and evaluate the results. The aim of the present study was to compare motor and cognitive deficits in two most common models of PD: the Rotenone and 6-OHDA model, using a large battery of neurological tests and a probabilistic learning task. To the best of our knowledge, this is the first study to examine the effects of bilaterally induced Rotenone and 6-OHDA through behavioral test batteries assessing the cardinal motor symptoms and the cognitive abnormality of Parkinson’s Disease in the same rat population. Also, the present study is unique on the basis of providing both longitudinal observations of behaviour in the same treatment group and the cross-sectional comparisons of the behavioural responses between different groups. In the current study, the neurotoxins were applied at relatively low doses of 3-4 μg, bilaterally to the substantia nigra pars compacta (SNpc). Experiments were conducted on 50 young-adult male Sprague–Dawley rats randomly assigned to five experimental groups: Rotenone, 6-OHDA, vehicle (DMSO/Saline), and the intact control. The neurological tests included locomotor activity,catalepsy, rearing, stepping, and rotarod/accelerod tests. They were applied prior to, and on days 4-7-10-20-40-150 while the learning task was applied 49 days after drug infusion.During the first 2 postoperational months, both neurotoxins produced progressive deterioration in motor performance but showing no effect on cognitive functions. Five months after the surgery, regression of bradykinesia but persistence of sensorimotor deficits was noted. The tests’ results suggest different susceptibility of different motor functions to the degeneration of nigro-striatal (N-S) pathway. So, different tests were demonstrated to have different power in detecting similar motor deficits.


Epileptic seizures induce structural and functional alterations on brain tissue membranes
Turker, Sevgi; Severcan, Mete; İLBAY, GÜL; Severcan, Feride (2014-12-01)
Epilepsy is characterized by disruption of balance between cerebral excitation and inhibition, leading to recurrent and unprovoked convulsions. Studies are still underway to understand mechanisms lying epileptic seizures with the aim of improving treatment strategies. In this context, the research on brain tissue membranes gains importance for generation of epileptic activities. In order to provide additional information for this field, we have investigated the effects of pentylenetetrazol-induced and audio...
Neuroprotective Efficacy of the Peroxisome Proliferator-Activated Receptor-gamma Ligand in Chronic Cerebral Hypoperfusion
SAYAN ÖZAÇMAK, HALE; SAYAN, Hale; BARUT, FİGEN; Jakubowska-Dogru, Ewa (Bentham Science Publishers Ltd., 2011-08-01)
Chronic cerebral hypoperfusion can cause learning and memory impairment and neuronal damage resembling the effects observed in vascular dementia. PPAR-gamma agonists were shown to modulate inflammatory response and neuronal death following cerebral ischemia. The present study was designed to evaluate possible neuroprotective effects of rosiglitazone, a PPAR-gamma agonist, in rat model of chronic cerebral hypoperfusion. Cerebral hypoperfusion was induced by permanent bilateral occlusion of the common carotid...
Association analysis of GSTT1, GSTM1 genotype polymorphisms and serum total GST activity with ischemic stroke risk
Turkanoglu, Aysun; Demirdogen, Birsen Can; Demirkaya, Seref; Bek, Semai; Adalı, Orhan (Springer Science and Business Media LLC, 2010-12-01)
Oxidative stress plays a major role in pathogenesis of atherosclerosis which is responsible for stroke. Glutathione S-transferases (GSTs) detoxify metabolites produced by oxidative stress within the cell and protect the cells against injury. This study aimed to investigate the association of polymorphisms in GSTT1, GSTM1 genes and GST activity with ischemic stroke risk. Patients had almost the same GST activity as that of controls. No significant differences were found between patients and controls in terms...
Aromatase and C/EBP expression after global ischemia/reperfusion injury in rat hippocampus
Kelicen, P.; Burul-Bozkurt, N.; Cincioglu, M.; Dagdeviren, M.; Pekiner, C. (2009-08-15)
Background and aims: Global ischemia after cardiac arrest, intraoperative hypoxia/hypotension, or hemorrhagic shock is one of the causes of brain injury, resulting in severe neurological and neurobehavioral deficit. Since neurodegeneration can be protected from by local aromatase expression and estrogen synthesis can be neuroprotective in the ischemia/reperfusion process, aromatase may be a potential target to study reperfusion injury after brain ischemia. We investigated the expression of aromatase and C/E...
Thalamic GABA levels and occupational manganese neurotoxicity: Association with exposure levels and brain MRI
Ma, Ruoyun E.; Ward, Eric J.; Yeh, Chien-Lin; Snyder, Sandy; Long, Zaiyang; Gökalp Yavuz, Fulya; Zauber, S. Elizabeth; Dydak, Ulrike (Elsevier BV, 2018-1)
Excessive occupational exposure to Manganese (Mn) has been associated with clinical symptoms resembling idiopathic Parkinson's disease (IPD), impairing cognitive and motor functions. Several studies point towards an involvement of the brain neurotransmitter system in Mn intoxication, which is hypothesized to be disturbed prior to onset of symptoms. Edited Magnetic Resonance Spectroscopy (MRS) offers the unique possibility to measure gamma-amminobutyric acid (GABA) and other neuro-metabolites in vivo non-inv...
Citation Formats
İ. Telkes, “Phase validation of neurotoxic animal models of Parkinson’s disease,” M.S. - Master of Science, Middle East Technical University, 2012.