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Mesencephalic astrocyte-derived neurotrophic factor enhances nigral γ-aminobutyric acid release

Zhou, Chunyia b; Xiao, Chenga b; Commissiong, John W.c; Krnjević, Krešimird; Ye, Jiang Honga b

doi: 10.1097/01.wnr.0000201504.23255.bc
Glial Cells

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 γ-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.

aDepartments of Anesthesiology

bPharmacology and Physiology, New Jersey Medical School, Newark, New Jersey, USA

cNeurotrophics Inc., Mississauge, Ontario

dPhysiology Department, McGill University, Montreal, Quebec, Canada

Correspondence and requests for reprints to Jiang Hong Ye, Department of Anesthesiology, New Jersey Medical School (UMDNJ), 185 South Orange Avenue, Newark, NJ 07103-2714, USA

Tel: +1 973 972 1866; fax: + 1 973 972 4172; e-mail: ye@umdnj.edu

Sponsorship: This publication was made possible by Grants AA-11989 from the National Institute of Alcohol Abuse and Alcoholism (NIAAA), AT-001182 from the National Center for Complementary and Alternative Medicine (NCCAM), and UMDNJ Foundation.

Received 18 November 2005; accepted 19 December 2005

© 2006 Lippincott Williams & Wilkins, Inc.