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Neurotoxicity Research

, Volume 34, Issue 1, pp 16–31 | Cite as

Temporal-Spatial Profiling of Pedunculopontine Galanin-Cholinergic Neurons in the Lactacystin Rat Model of Parkinson’s Disease

  • Joanna L. Elson
  • Rafael Kochaj
  • Richard Reynolds
  • Ilse S. Pienaar
ORIGINAL ARTICLE

Abstract

Parkinson’s disease (PD) is conventionally seen as resulting from single-system neurodegeneration affecting nigrostriatal dopaminergic neurons. However, accumulating evidence indicates multi-system degeneration and neurotransmitter deficiencies, including cholinergic neurons which degenerate in a brainstem nucleus, the pedunculopontine nucleus (PPN), resulting in motor and cognitive impairments. The neuropeptide galanin can inhibit cholinergic transmission, while being upregulated in degenerating brain regions associated with cognitive decline. Here we determined the temporal-spatial profile of progressive expression of endogenous galanin within degenerating cholinergic neurons, across the rostro-caudal axis of the PPN, by utilizing the lactacystin-induced rat model of PD. First, we show progressive neuronal death affecting nigral dopaminergic and PPN cholinergic neurons, reflecting that seen in PD patients, to facilitate use of this model for assessing the therapeutic potential of bioactive peptides. Next, stereological analyses of the lesioned brain hemisphere found that the number of PPN cholinergic neurons expressing galanin increased by 11%, compared to sham-lesioned controls, and increasing by a further 5% as the neurodegenerative process evolved. Galanin upregulation within cholinergic PPN neurons was most prevalent closest to the intra-nigral lesion site, suggesting that galanin upregulation in such neurons adapt intrinsically to neurodegeneration, to possibly neuroprotect. This is the first report on the extent and pattern of galanin expression in cholinergic neurons across distinct PPN subregions in both the intact rat CNS and lactacystin-lesioned rats. The findings pave the way for future work to target galanin signaling in the PPN, to determine the extent to which upregulated galanin expression could offer a viable treatment strategy for ameliorating PD symptoms associated with cholinergic degeneration.

Keywords

Cholinergic co-expression Galanin Lactacystin Parkinson’s disease Pedunculopontine nucleus 

Abbreviations

ACh

acetylcholine

AD

Alzheimer’s disease

Aa

amino acid

amyloid-β

AOI

area of interest

Bcl-2

B-cell lymphoma 2

Bax

Bcl-2-associated X

ChAT

choline acetyltransferase

CFV

Cresyl fast violet

DAB

33’-diaminobenzidine

DAPI

4′,6-diamidino-2-phenylindole

DBS

deep brain stimulation

DLB

dementia with Lewy bodies

DA

dopamine

EtOH

ethanol

GAL

galanin [gene]

GAL2

galanin receptor 2

GABA

gamma-aminobutyric acid

GPCRs

G-protein coupled receptors

Ir

immunoreactive

i.p.

intraperitoneal

LDTg

laterodorsal tegmental nucleus

LBD

Lewy body disorders

NbM

nucleus basalis of Meynert

PFA

paraformaldehyde

PD

Parkinson’s disease

PDD

PD with dementia

PPN

pedunculopontine nucleus

PBS

phosphate-buffered saline

RT

room temperature

SNpc

substantia nigra pars compacta

SNr

substantia nigra pars reticulata

T

time

TBS

tris-buffered saline

TH

tyrosine hydroxylase

VTA

ventral tegmental area

Notes

Acknowledgements

This study received grant support from the British Pharmacological Society and the Rosetrees Trust, awarded to ISP.

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Joanna L. Elson
    • 1
    • 2
  • Rafael Kochaj
    • 3
  • Richard Reynolds
    • 4
  • Ilse S. Pienaar
    • 4
    • 5
  1. 1.Institute of Genetic MedicineNewcastle UniversityNewcastle upon TyneUK
  2. 2.Centre for Human MetabolomicsNorth-West UniversityPotchefstroomSouth Africa
  3. 3.Wolfson Centre for Age-Related Diseases, King’s College London, Guys CampusLondonUK
  4. 4.Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Faculty of Medicine, Imperial College LondonLondonUK
  5. 5.School of Life SciencesUniversity of SussexBrightonUK

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