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Neurotoxicity Research

, Volume 34, Issue 1, pp 47–61 | Cite as

Peripheral Administration of Tetanus Toxin Hc Fragment Prevents MPP+ Toxicity In Vivo

  • Natalia Moreno-Galarza
  • Liliana Mendieta
  • Victoria Palafox-Sánchez
  • Mireia Herrando-Grabulosa
  • Carles Gil
  • Daniel I. Limón
  • José Aguilera
ORIGINAL ARTICLE
  • 80 Downloads

Abstract

Several studies have shown that intrastriatal application of 1-methyl-4-phenylpyridinium (MPP+) produces similar biochemical changes in rat to those seen in Parkinson’s disease (PD), such as dopaminergic terminal degeneration and consequent appearance of motor deficits, making the MPP+ lesion a widely used model of parkinsonism in rodents. Previous results from our group have shown a neuroprotective effect of the carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) under different types of stress. In the present study, pretreatment with the intraperitoneal injection of Hc-TeTx in rats prevents the decrease of tyrosine hydroxylase immunoreactivity in the striatum due to injury with MPP+, when applied stereotaxically in the striatum. Similarly, striatal catecholamine contents are restored, as well as the levels of two other dopaminergic markers, the dopamine transporter (DAT) and the vesicular monoamine transporter-2 (VMAT-2). Additionally, uptake studies of [3H]-dopamine and [3H]-MPP+ reveal that DAT action is not affected by Hc-TeTx, discarding a protective effect due to a reduced entry of MPP+ into nerve terminals. Behavioral assessments show that Hc-TeTx pretreatment improves the motor skills (amphetamine-induced rotation, forelimb use, and adjusting steps) of MPP+-treated rats. Our results lead us to consider Hc-TeTx as a potential therapeutic tool in pathologies caused by impairment of dopaminergic innervation in the striatum, as is the case of PD.

Keywords

Carboxyl-terminal domain of tetanus toxin Parkinson’s disease Tyrosine hydroxylase Dopamine Neuroprotection 1-Methyl-4-phenylpyridinium 

Abbreviations

DA

dopamine

DAT

dopamine transporter

DOPAC

3,4-dihydroxyphenylacetic acid

Hc-TeTx or Hc

carboxyl-terminal domain of the heavy-chain of tetanus toxin

HVA

homovanillic acid

MPP+

1-methyl-4-phenylpyridinium

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

3 MT

3-methoxytyramine

PD

Parkinson’s disease

SNpc

substantia nigra pars compacta

TH

tyrosine hydroxylase

VMAT-2

vesicular monoamine transporter-2

Notes

Acknowledgements

We thank Chuck Simmons for his help in the English preparation of this manuscript.

Funding Information

This work was supported by Grants SAF2013-43900-R and SAF2016-80027-R from the Ministerio de Ciencia e Innovación (Dirección General de Investigación) of the Spanish Government. L. Mendieta received a grant from PRODEP-SEP (PTC-472) and V. Palafox-Sánchez received a scholarship from CONACYT-Mexico (244867).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Natalia Moreno-Galarza
    • 1
  • Liliana Mendieta
    • 2
  • Victoria Palafox-Sánchez
    • 2
  • Mireia Herrando-Grabulosa
    • 1
  • Carles Gil
    • 1
  • Daniel I. Limón
    • 2
  • José Aguilera
    • 1
    • 3
  1. 1.Institut de Neurociències and Departament de Bioquímica i de Biologia Molecular, Facultat de MedicinaUniversitat Autònoma de BarcelonaBarcelonaSpain
  2. 2.Laboratorio de NeurofarmacologíaFCQ-Benemérita Universidad Autónoma de PueblaPueblaMexico
  3. 3.Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)BarcelonaSpain

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