1. Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Elevates Stimulus-Evoked Release of Dopamine in Freely-Moving Rats
- Author
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Juho-Matti Renko, Merja H. Voutilainen, Susanne Bäck, T. Petteri Piepponen, Raimo K. Tuominen, Ilkka Reenilä, Mart Saarma, Regenerative pharmacology group, Faculty of Pharmacy, Division of Pharmacology and Pharmacotherapy, Doctoral Programme Brain & Mind, Doctoral Programme in Drug Research, Institute of Biotechnology, Timo Petteri Piepponen / Principal Investigator, Drug Research Program, Research Services, Mart Saarma / Principal Investigator, Doctoral Programme in Integrative Life Science, and Regenerative Neuroscience
- Subjects
Male ,0301 basic medicine ,Dopamine ,0302 clinical medicine ,TYROSINE-HYDROXYLASE PHOSPHORYLATION ,ENDOPLASMIC-RETICULUM STRESS ,PARKINSONS-DISEASE ,Neurotrophic factors ,Cerebral dopamine neurotrophic factor (CDNF) ,CDNF/MANF FAMILY ,Glial cell line-derived neurotrophic factor ,SUBSTANTIA-NIGRA ,biology ,Chemistry ,Dopaminergic ,INDUCED CELL-DAMAGE ,3. Good health ,Neurology ,Metabolome ,RHESUS-MONKEYS ,Neurotrophin ,medicine.drug ,medicine.medical_specialty ,Tyrosine 3-Monooxygenase ,Movement ,Neuroscience (miscellaneous) ,Dopamine microdialysis ,Substantia nigra ,Catechol O-Methyltransferase ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Internal medicine ,Catechol-O-methyltransferase (COMT) ,medicine ,Animals ,Humans ,Glial Cell Line-Derived Neurotrophic Factor ,Nerve Growth Factors ,Rats, Wistar ,Monoamine Oxidase ,Cerebral dopamine neurotrophic factor ,Tyrosine hydroxylase ,3112 Neurosciences ,NEURONS IN-VIVO ,Rats ,Tyrosine hydroxylase (TH) ,030104 developmental biology ,Endocrinology ,nervous system ,CATECHOL-O-METHYLTRANSFERASE ,CDNF PROTECTS ,biology.protein ,030217 neurology & neurosurgery ,Glial cell line-derived neurotrophic factor (GDNF) ,Mesencephalic astrocyte-derived neurotrophic factor (MANF) - Abstract
Neurotrophic factors (NTFs) hold potential as disease-modifying therapies for neurodegenerative disorders like Parkinson’s disease. Glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), and mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown neuroprotective and restorative effects on nigral dopaminergic neurons in various animal models of Parkinson’s disease. To date, however, their effects on brain neurochemistry have not been compared using in vivo microdialysis. We measured extracellular concentration of dopamine and activity of dopamine neurochemistry-regulating enzymes in the nigrostriatal system of rat brain. NTFs were unilaterally injected into the striatum of intact Wistar rats. Brain microdialysis experiments were performed 1 and 3 weeks later in freely-moving animals. One week after the treatment, we observed enhanced stimulus-evoked release of dopamine in the striatum of MANF-treated rats, but not in rats treated with GDNF or CDNF. MANF also increased dopamine turnover. Although GDNF did not affect the extracellular level of dopamine, we found significantly elevated tyrosine hydroxylase (TH) and catechol-O-methyltransferase (COMT) activity and decreased monoamine oxidase A (MAO-A) activity in striatal tissue samples 1 week after GDNF injection. The results show that GDNF, CDNF, and MANF have divergent effects on dopaminergic neurotransmission, as well as on dopamine synthetizing and metabolizing enzymes. Although the cellular mechanisms remain to be clarified, knowing the biological effects of exogenously administrated NTFs in intact brain is an important step towards developing novel neurotrophic treatments for degenerative brain diseases. Electronic supplementary material The online version of this article (10.1007/s12035-018-0872-8) contains supplementary material, which is available to authorized users.
- Published
- 2018