RGD Reference Report - Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson's disease. - Rat Genome Database

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Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson's disease.

Authors: Voutilainen, MH  Back, S  Porsti, E  Toppinen, L  Lindgren, L  Lindholm, P  Peranen, J  Saarma, M  Tuominen, RK 
Citation: Voutilainen MH, etal., J Neurosci. 2009 Jul 29;29(30):9651-9.
RGD ID: 2325813
Pubmed: PMID:19641128   (View Abstract at PubMed)
PMCID: PMC6666534   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.0833-09.2009   (Journal Full-text)

Neurotrophic factors are promising candidates for the treatment of Parkinson's disease (PD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) belongs to a novel evolutionarily conserved family of neurotrophic factors. We examined whether MANF has neuroprotective and neurorestorative effect in an experimental model of PD in rats. We also studied the distribution and transportation of intrastriatally injected MANF in the brain and compared it with glial cell line-derived neurotrophic factor (GDNF). Unilateral lesion of nigrostriatal dopaminergic system was induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). Amphetamine-induced turning behavior was monitored up to 12 weeks after the unilateral lesion. The local diffusion at the injection site and transportation profiles of intrastriatally injected MANF and GDNF were studied by immunohistochemical detection of the unlabeled growth factors as well as by autoradiographic and gamma counting detection of (125)I-labeled trophic factors. Intrastriatally injected MANF protected nigrostriatal dopaminergic nerves from 6-OHDA-induced degeneration as evaluated by counting tyrosine hydroxylase (TH)-positive cell bodies in the substantia nigra (SN) and TH-positive fibers in the striatum. More importantly, MANF also restored the function of the nigrostriatal dopaminergic system when administered either 6 h before or 4 weeks after 6-OHDA administration in the striatum. MANF was distributed throughout the striatum more readily than GDNF. The mechanism of MANF action differs from that of GDNF because intrastriatally injected (125)I-MANF was transported to the frontal cortex, whereas (125)I-GDNF was transported to the SN. Our results suggest that MANF is readily distributed throughout the striatum and has significant therapeutic potential for the treatment of PD.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MANFHumanParkinsonism  IMP  RGD 
ManfRatParkinsonism  ISOMANF (Homo sapiens) RGD 
ManfMouseParkinsonism  ISOMANF (Homo sapiens) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ManfRatextracellular space  IDA  RGD 
ManfRatperinuclear region of cytoplasm  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Manf  (mesencephalic astrocyte-derived neurotrophic factor)

Genes (Mus musculus)
Manf  (mesencephalic astrocyte-derived neurotrophic factor)

Genes (Homo sapiens)
MANF  (mesencephalic astrocyte derived neurotrophic factor)


Additional Information