Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson's disease
| Autor: | Lauri Lindgren, Liisa Toppinen, Mart Saarma, Johan Peränen, Raimo K. Tuominen, Susanne Bäck, Eeva Pörsti, Päivi Lindholm, Merja H. Voutilainen |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Time Factors Dopamine Substantia nigra Nerve Tissue Proteins Striatum Pharmacology Motor Activity 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neurotrophic factors Glial cell line-derived neurotrophic factor Animals Humans Glial Cell Line-Derived Neurotrophic Factor Nerve Growth Factors Parkinson Disease Secondary Rats Wistar Oxidopamine Cerebral dopamine neurotrophic factor 030304 developmental biology Neurons 0303 health sciences Tyrosine hydroxylase biology General Neuroscience Articles Corpus Striatum Recombinant Proteins Rats Substantia Nigra Disease Models Animal Nerve growth factor Neuroprotective Agents chemistry nervous system Nerve Degeneration biology.protein Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience; Vol 29 |
| ISSN: | 1529-2401 |
| Popis: | 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 of125I-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 injected125I-MANF was transported to the frontal cortex, whereas125I-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. |
| Databáze: | OpenAIRE |
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