caa a22 4500 606201351 CHVBK 20210128100947.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00429-013-0669-5 doi (NATIONALLICENCE)springer-10.1007/s00429-013-0669-5 An animal model mimicking pedunculopontine nucleus cholinergic degeneration in Parkinson's disease [Elektronische Daten] [Ilse Pienaar, Ian Harrison, Joanna Elson, Alexander Bury, Petter Woll, Anna Simon, David Dexter] A rostral brainstem structure, the pedunculopontine nucleus (PPN), is severely affected by Parkinson's disease (PD) pathology and is regarded a promising target for therapeutic deep-brain stimulation (DBS). However, understanding the PPN's role in PD and assessing the potential of DBS are hampered by the lack of a suitable model of PPN degeneration. Rats were rendered Parkinsonian through a unilateral substantia nigra pars compacta (SNpc) stereotaxic injection of the proteasome inhibitor Lactacystin, to investigate whether the lesion's pathological effects spread to impact the integrity of PPN cholinergic neurons which are affected in PD. At 5weeks post-surgery, stereological analysis revealed that the lesion caused a 48% loss of dopaminergic SNpc neurons and a 61% loss of PPN cholinergic neurons, accompanied by substantial somatic hypotrophy in the remaining cholinergic neurons. Magnetic resonance imaging revealed T2 signal hyper-/hypointensity in the PPN of the injected hemisphere, respectively at weeks 3 and 5 post-lesion. Moreover, isolated PPN cholinergic neurons revealed no significant alterations in key autophagy mRNA levels, suggesting that autophagy-related mechanisms fail to protect the PPN against Lactacystin-induced cellular changes. Hence, the current results suggest that the Lactacystin PD model offers a suitable model for investigating the role of the PPN in PD. Springer-Verlag Berlin Heidelberg, 2013 Neurodegeneration nationallicence Cholinergic neurons nationallicence Parkinson's disease nationallicence Pedunculopontine nucleus nationallicence Proteasomal inhibitor nationallicence ACh : Acetylcholine nationallicence AOI : Area of interest nationallicence asf : Area sampling fraction nationallicence αSYN : α-synuclein nationallicence ATG : Autophagy-specific gene nationallicence ABC : Avidin-biotin peroxidise complex nationallicence CNS : Central nervous system nationallicence ChAT : Choline acetyl transferase nationallicence CE : Coefficient of error nationallicence CFV : Cresyl fast violet nationallicence DBS : Deep-brain stimulation nationallicence i.p : Intraperitoneally nationallicence DAB : 3,3′-Diaminobenzidine nationallicence EtOH : Ethanol nationallicence hsf : Height sampling fraction nationallicence LCM : Laser-capture microdissection nationallicence LDTg : Laterodorsal tegmental nucleus nationallicence MR : Magnetic resonance nationallicence MRI : Magnetic resonance imaging nationallicence MHC : Major histocompatibility complex nationallicence MFB : Medial forebrain bundle nationallicence MPTP : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine nationallicence MEMS : Multi-echo multi-slice spin-echo pulse sequence nationallicence NeuN : Neuronal-specific nuclear nationallicence NADPH : Nicotinamide adenine dinucleotide phosphate nationallicence NGS : Normal goat serum nationallicence NHS : Normal horse serum nationallicence PD : Parkinson's disease nationallicence PBS : Phosphate buffer saline nationallicence PBST : Phosphate buffer solution with 0.1% Triton X-100 nationallicence PPN : Pedunculopontine nucleus nationallicence PTFE : Polytetrafluroethylane nationallicence PSP : Progressive supranuclear palsy nationallicence REM : Rapid eye movement sleep nationallicence ROS : Reactive oxygen species nationallicence ROI : Region of interest nationallicence RT : Room temperature nationallicence 6-OHDA : 6-Hydroxydopamine nationallicence ssf : Section sampling fraction nationallicence SNpc : Substantia nigra pars compacta nationallicence SNr : Substantia Nigra pars reticulata nationallicence TE : Tris-EDTA nationallicence T2W : T2-weighted nationallicence TH : Tyrosine hydroxylase nationallicence UCH-L1 : Ubiquitin C-terminal hydrolase L1 nationallicence UPS : Ubiquitin-proteasome system nationallicence Pienaar Ilse Division of Brain Sciences, Department of Medicine, Centre for Neuroinflammation and Neurodegeneration, Imperial College London, W12 ONN, London, UK aut Harrison Ian Division of Brain Sciences, Department of Medicine, Centre for Neuroinflammation and Neurodegeneration, Imperial College London, W12 ONN, London, UK aut Elson Joanna Institute of Genetic Medicine, Newcastle University, NE1 3BZ, Newcastle-upon-Tyne, UK aut Bury Alexander Division of Brain Sciences, Department of Medicine, Centre for Neuroinflammation and Neurodegeneration, Imperial College London, W12 ONN, London, UK aut Woll Petter The Weatherall Institute of Molecular Medicine, University of Oxford Headington, OX3 9DS, Oxford, UK aut Simon Anna The Weatherall Institute of Molecular Medicine, University of Oxford Headington, OX3 9DS, Oxford, UK aut Dexter David Division of Brain Sciences, Department of Medicine, Centre for Neuroinflammation and Neurodegeneration, Imperial College London, W12 ONN, London, UK aut Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 479-500 1863-2653 220:1<479 2015 220 429 https://doi.org/10.1007/s00429-013-0669-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-013-0669-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pienaar Ilse Division of Brain Sciences, Department of Medicine, Centre for Neuroinflammation and Neurodegeneration, Imperial College London, W12 ONN, London, UK aut NATIONALLICENCE 700 1- Harrison Ian Division of Brain Sciences, Department of Medicine, Centre for Neuroinflammation and Neurodegeneration, Imperial College London, W12 ONN, London, UK aut NATIONALLICENCE 700 1- Elson Joanna Institute of Genetic Medicine, Newcastle University, NE1 3BZ, Newcastle-upon-Tyne, UK aut NATIONALLICENCE 700 1- Bury Alexander Division of Brain Sciences, Department of Medicine, Centre for Neuroinflammation and Neurodegeneration, Imperial College London, W12 ONN, London, UK aut NATIONALLICENCE 700 1- Woll Petter The Weatherall Institute of Molecular Medicine, University of Oxford Headington, OX3 9DS, Oxford, UK aut NATIONALLICENCE 700 1- Simon Anna The Weatherall Institute of Molecular Medicine, University of Oxford Headington, OX3 9DS, Oxford, UK aut NATIONALLICENCE 700 1- Dexter David Division of Brain Sciences, Department of Medicine, Centre for Neuroinflammation and Neurodegeneration, Imperial College London, W12 ONN, London, UK aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 479-500 1863-2653 220:1<479 2015 220 429