PMID- 10377350 OWN - NLM STAT- MEDLINE DCOM- 19990715 LR - 20231104 IS - 0270-6474 (Print) IS - 1529-2401 (Electronic) IS - 0270-6474 (Linking) VI - 19 IP - 13 DP - 1999 Jul 1 TI - Expression of the striatal DARPP-32/ARPP-21 phenotype in GABAergic neurons requires neurotrophins in vivo and in vitro. PG - 5409-19 AB - The medium spiny neuron (MSN) is the major output neuron of the caudate nucleus and uses GABA as its primary neurotransmitter. A majority of MSNs coexpress DARPP-32 and ARPP-21, two dopamine and cyclic AMP-regulated phosphoproteins, and most of the matrix neurons express calbindin. DARPP-32 is the most commonly used MSN marker, but previous attempts to express this gene in vitro have failed. In this study we found that DARPP-32 is expressed in <12% of E13- or E17-derived striatal neurons when they are grown in defined media at high or low density in serum, dopamine, or Neurobasal/N2 (Life Technologies), and ARPP-21 is expressed in <1%. The percentage increases to 25% for DARPP-32 and 10% for ARPP-21 when the same cells are grown in Neurobasal/B27 (Life Technologies) for 7 d. After growth in Neurobasal/B27 plus brain-derived neurotrophic factor (BDNF) for 7 d, E13-derived MSNs are 53.7% DARPP-32-positive and 29. 0% ARPP-21-positive; E17-derived MSNs are 66.8% DARPP-32-positive and 51.5% ARPP-21-positive. The percentage of calbindin-positive neurons also is increased under these conditions. Finally, ARPP-21 expression is reduced in mice with a targeted deletion of the BDNF gene. We conclude that BDNF is required for the maturation of a large subset of patch and matrix MSNs in vivo and in vitro. In addition, we introduce a culture system in which highly differentiated MSNs may be generated, maintained, and studied. FAU - Ivkovic, S AU - Ivkovic S AD - The Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA. FAU - Ehrlich, M E AU - Ehrlich ME LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calbindins) RN - 0 (Culture Media) RN - 0 (Dopamine and cAMP-Regulated Phosphoprotein 32) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Phosphoproteins) RN - 0 (S100 Calcium Binding Protein G) RN - 125004-22-0 (cyclic AMP-regulated phosphoprotein ARPP-21) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*pharmacology/physiology MH - Calbindins MH - Caudate Nucleus/*cytology MH - Cell Count/drug effects MH - Cell Culture Techniques/methods MH - Cell Differentiation/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Culture Media MH - Dopamine/pharmacology MH - Dopamine and cAMP-Regulated Phosphoprotein 32 MH - Female MH - Gene Deletion MH - Gene Expression Regulation/*drug effects MH - Mice MH - Nerve Growth Factors/pharmacology MH - Nerve Tissue Proteins/*metabolism MH - Neurons/cytology/drug effects/*metabolism MH - Phosphoproteins/*metabolism MH - S100 Calcium Binding Protein G/metabolism MH - gamma-Aminobutyric Acid/*physiology PMC - PMC6782303 EDAT- 1999/06/23 00:00 MHDA- 1999/06/23 00:01 PMCR- 2000/01/01 CRDT- 1999/06/23 00:00 PHST- 1999/06/23 00:00 [pubmed] PHST- 1999/06/23 00:01 [medline] PHST- 1999/06/23 00:00 [entrez] PHST- 2000/01/01 00:00 [pmc-release] AID - 3170 [pii] AID - 10.1523/JNEUROSCI.19-13-05409.1999 [doi] PST - ppublish SO - J Neurosci. 1999 Jul 1;19(13):5409-19. doi: 10.1523/JNEUROSCI.19-13-05409.1999.