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An animal model mimicking pedunculopontine nucleus cholinergic degeneration in Parkinson’s disease


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 5 weeks 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.

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Area of interest


Area sampling fraction




Autophagy-specific gene


Avidin–biotin peroxidise complex


Central nervous system


Choline acetyl transferase


Coefficient of error


Cresyl fast violet


Deep-brain stimulation








Height sampling fraction


Laser-capture microdissection


Laterodorsal tegmental nucleus


Magnetic resonance


Magnetic resonance imaging


Major histocompatibility complex


Medial forebrain bundle




Multi-echo multi-slice spin-echo pulse sequence


Neuronal-specific nuclear


Nicotinamide adenine dinucleotide phosphate


Normal goat serum


Normal horse serum


Parkinson’s disease


Phosphate buffer saline


Phosphate buffer solution with 0.1 % Triton X-100


Pedunculopontine nucleus




Progressive supranuclear palsy


Rapid eye movement sleep


Reactive oxygen species


Region of interest


Room temperature




Section sampling fraction


Substantia nigra pars compacta


Substantia Nigra pars reticulata






Tyrosine hydroxylase


Ubiquitin C-terminal hydrolase L1


Ubiquitin–proteasome system


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ISP holds an Imperial College London Jnr. Research Fellowship. This study received grant support from the Rosetrees Trust, awarded to ISP. IFH is supported by a UK Medical Research Council (MRC) Ph.D. studentship. AKS is supported by the National Institute for Health Research (NIHR) and the Oxford Biomedical Research Centre. All the authors commented on the paper and agreed on the final version of the manuscript.

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Correspondence to Ilse S. Pienaar.

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Pienaar, I.S., Harrison, I.F., Elson, J.L. et al. An animal model mimicking pedunculopontine nucleus cholinergic degeneration in Parkinson’s disease. Brain Struct Funct 220, 479–500 (2015).

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  • Neurodegeneration
  • Cholinergic neurons
  • Parkinson’s disease
  • Pedunculopontine nucleus
  • Proteasomal inhibitor