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Tytuł pozycji:

Nuclear Receptor Nr4a1 Regulates Striatal Striosome Development and Dopamine D 1 Receptor Signaling.

Tytuł:
Nuclear Receptor Nr4a1 Regulates Striatal Striosome Development and Dopamine D 1 Receptor Signaling.
Autorzy:
Cirnaru MD; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
Melis C; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
Fanutza T; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
Naphade S; The Buck Institute for Research on Aging, Novato, California 94945.
Tshilenge KT; The Buck Institute for Research on Aging, Novato, California 94945.
Muntean BS; Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida 33458.
Martemyanov KA; Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida 33458.
Plotkin JL; Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York 11794.
Ellerby LM; The Buck Institute for Research on Aging, Novato, California 94945.
Ehrlich ME; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York 10029 .
Źródło:
ENeuro [eNeuro] 2019 Oct 10; Vol. 6 (5). Date of Electronic Publication: 2019 Oct 10 (Print Publication: 2019).
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: [Washington, DC] : Society for Neuroscience, [2014]-
MeSH Terms:
Corpus Striatum/*metabolism
Neurons/*metabolism
Nuclear Receptor Subfamily 4, Group A, Member 1/*biosynthesis
Receptors, Dopamine D1/*biosynthesis
Signal Transduction/*physiology
Animals ; Animals, Newborn ; Cells, Cultured ; Cocaine/pharmacology ; Corpus Striatum/cytology ; Corpus Striatum/drug effects ; Dopamine Uptake Inhibitors/pharmacology ; Humans ; Locomotion/drug effects ; Locomotion/physiology ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Neurons/drug effects ; Nuclear Receptor Subfamily 4, Group A, Member 1/deficiency ; Signal Transduction/drug effects
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Grant Information:
K02 DA026405 United States DA NIDA NIH HHS; R01 NS100529 United States NS NINDS NIH HHS
Contributed Indexing:
Keywords: ERK; Nr4a1; dopamine receptor D1; signal; striosome; transduction
Substance Nomenclature:
0 (Dopamine Uptake Inhibitors)
0 (Drd1 protein, mouse)
0 (Nr4a1 protein, mouse)
0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
0 (Receptors, Dopamine D1)
I5Y540LHVR (Cocaine)
Entry Date(s):
Date Created: 20190922 Date Completed: 20200330 Latest Revision: 20200714
Update Code:
20240105
PubMed Central ID:
PMC6787343
DOI:
10.1523/ENEURO.0305-19.2019
PMID:
31541002
Czasopismo naukowe
The GABAergic medium-size spiny neuron (MSN), the striatal output neuron, may be classified into striosome, also known as patch, and matrix, based on neurochemical differences between the two compartments. At this time, little is known regarding the regulation of the development of the two compartments. Nr4a1 , primarily described as a nuclear receptor/immediate early gene involved in the homeostasis of the dopaminergic system, is a striosomal marker. Using Nr4a1 -overexpressing and Nr4a1 -null mice, we sought to determine whether Nr4a1 is necessary and/or sufficient for striosome development. We report that in vivo and in vitro , Nr4a1 and Oprm1 mRNA levels are correlated. In the absence of Nr4a, there is a decrease in the percentage of striatal surface area occupied by striosomes. Alterations in Nr4a1 expression leads to dysregulation of multiple mRNAs of members of the dopamine receptor D 1 signal transduction system. Constitutive overexpression of Nr4a1 decreases both the induction of phosphorylation of ERK after a single cocaine exposure and locomotor sensitization following chronic cocaine exposure. Nr4a1 overexpression increases MSN excitability but reduces MSN long-term potentiation. In the resting state, type 5 adenylyl cyclase (AC5) activity is normal, but the ability of AC5 to be activated by Drd1 G-protein-coupled receptor inputs is decreased. Our results support a role for Nr4a1 in determination of striatal patch/matrix structure and in regulation of dopaminoceptive neuronal function.
(Copyright © 2019 Cirnaru et al.)

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