+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Elevates Stimulus-Evoked Release of Dopamine in Freely-Moving Rats

Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Elevates Stimulus-Evoked Release of Dopamine in Freely-Moving Rats

Molecular Neurobiology 55(8): 6755-6768

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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 065310046

Download citation: RISBibTeXText

PMID: 29349573

DOI: 10.1007/s12035-018-0872-8

Related references

Photoreceptor Protection by Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF). Eneuro 5(2):, 2018

Neuronal phenotype selectivity of manf a new mesencephalic astrocyte derived neurotrophic factor. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 292 1, 2002

MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons. Journal of Molecular Neuroscience 20(2): 173-188, 2003

Mesencephalic astrocyte-derived neurotrophic factor (MANF) has a unique mechanism to rescue apoptotic neurons. Journal of Biological Chemistry 286(4): 2675-2680, 2011

Emerging Roles for Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Pancreatic Beta Cells and Diabetes. Frontiers in Physiology 9: 1457, 2018

Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects against Aβ toxicity via attenuating Aβ-induced endoplasmic reticulum stress. Journal of Neuroinflammation 16(1): 35, 2019

Mesencephalic astrocyte-derived neurotrophic factor (MANF) secretion and cell surface binding are modulated by KDEL receptors. Journal of Biological Chemistry 288(6): 4209-4225, 2013

Mesencephalic astrocyte-derived neurotrophic factor (MANF), a new player in endoplasmic reticulum diseases: structure, biology, and therapeutic roles. Translational Research 188: 1-9, 2017

An evolutionary perspective on the role of mesencephalic astrocyte-derived neurotrophic factor (MANF): At the crossroads of poriferan innate immune and apoptotic pathways. Biochemistry and Biophysics Reports 11: 161-173, 2017

Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Protects Against Neuronal Apoptosis via Activation of Akt/MDM2/p53 Signaling Pathway in a Rat Model of Intracerebral Hemorrhage. Frontiers in Molecular Neuroscience 11: 176, 2018

Mesencephalic astrocyte-derived neurotrophic factor and cerebral dopamine neurotrophic factor: New endoplasmic reticulum stress response proteins. European Journal of Pharmacology 750: 118-122, 2015

Neuroprotective and reparative effects of endoplasmic reticulum luminal proteins - mesencephalic astrocyte-derived neurotrophic factor and cerebral dopamine neurotrophic factor. Croatian Medical Journal 60(2): 99, 2019

Glial cell line-derived neurotrophic factor increases stimulus-evoked dopamine release and motor speed in aged rhesus monkeys. Journal of Neuroscience 23(5): 1974-1980, 2003

Mesencephalic astrocyte-derived neurotrophic factor enhances nigral gamma-aminobutyric acid release. Neuroreport 17(3): 293-297, 2006

Intranigral ventral mesencephalic grafts and nigrostriatal injections of glial cell line-derived neurotrophic factor restore dopamine release in the striatum of 6-hydroxydopamine-lesioned rats. Experimental Brain Research. 119(3): 287-296, Il, 1998