Mesencephalic astrocyte-derived neurotrophic factor enhances nigral gamma-aminobutyric acid release.
Mesencephalic astrocyte-derived neurotrophic factor (MANF) - one of a new class of astrocyte-derived human proteins--selectively promotes the survival of dopamine neurons of the ventral midbrain. Using the whole-cell clamp technique, we looked for acute effects of MANF on gamma-aminobutyric acid type A (GABAA) receptor-mediated inhibitory postsynaptic currents (IPSCs) in dopamine neurons of the substantia nigra pars compacta of 6 to 15-day-old rats. In slices, MANF increased the amplitude of evoked IPSCs and decreased the paired pulse ratio. In mechanically dissociated cells, MANF increased the frequency of spontaneous and miniature IPSCs, without changing their mean amplitudes; and in enzymatically dissociated neurons, MANF had no effect on currents induced by exogenous GABA. The presynaptic enhancement of GABAergic inhibition may contribute to MANF's protective action on dopamine cells.
Zhou
Chunyi
C
Department of Anesthesiology, New Jersey Medical School, Newark, New Jersey, USA.
Xiao
Cheng
C
Commissiong
John W
JW
Krnjević
Kresimir
K
Ye
Jiang Hong
JH
D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008636:Mesencephalon / Q000166:cytology*; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018491:Dopamine Agonists; D018756:GABA Antagonists; D051100:Glial Cell Line-Derived Neurotrophic Factor; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019257:Quinpirole; D005680:gamma-Aminobutyric Acid; D004298:Dopamine; D001640:Bicuculline