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Neuroscience. 2013 Oct 22;251:2-20. doi: 10.1016/j.neuroscience.2013.07.011. Epub 2013 Jul 16.

Differential striatal spine pathology in Parkinson's disease and cocaine addiction: a key role of dopamine?

Author information

1
Yerkes National Primate Research Center, Emory University, 954, Gatewood Road NE, Atlanta, GA 30329, USA; UDALL Center of Excellence for Parkinson's Disease, Emory University, 954, Gatewood Road NE, Atlanta, GA 30329, USA. Electronic address: rvillal@emory.edu.

Erratum in

  • Neuroscience. 2014 Feb 14;259:12.

Abstract

In the striatum, the dendritic tree of the two main populations of projection neurons, called "medium spiny neurons (MSNs)", are covered with spines that receive glutamatergic inputs from the cerebral cortex and thalamus. In Parkinson's disease (PD), striatal MSNs undergo an important loss of dendritic spines, whereas aberrant overgrowth of striatal spines occurs following chronic cocaine exposure. This review examines the possibility that opposite dopamine dysregulation is one of the key factors that underlies these structural changes. In PD, nigrostriatal dopamine degeneration results in a significant loss of dendritic spines in the dorsal striatum, while rodents chronically exposed to cocaine and other psychostimulants, display an increase in the density of "thin and immature" spines in the nucleus accumbens (NAc). In rodent models of PD, there is evidence that D2 dopamine receptor-containing MSNs are preferentially affected, while D1-positive cells are the main targets of increased spine density in models of addiction. However, such specificity remains to be established in primates. Although the link between the extent of striatal spine changes and the behavioral deficits associated with these disorders remains controversial, there is unequivocal evidence that glutamatergic synaptic transmission is significantly altered in both diseased conditions. Recent studies have suggested that opposite calcium-mediated regulation of the transcription factor myocyte enhancer factor 2 (MEF2) function induces these structural defects. In conclusion, there is strong evidence that dopamine is a major, but not the sole, regulator of striatal spine pathology in PD and addiction to psychostimulants. Further studies of the role of glutamate and other genes associated with spine plasticity in mediating these effects are warranted.

KEYWORDS:

6-OHDA; 6-hydroxydopamine; CaM; CaN; Calcineurin; Calmodulin; Cdk5; DA; GP; MEF2; MSNs; NAc; PD; PKA; PSD; Parkinson’s disease; Protein kinase A; RCS; RRA; Regulator of Calmodulin Signaling; SN; SNc; SNr; STN; SynCAM1; VTA; accumbens; cAMP; cocaine; corticostriatal; cyclic AMP; cyclin-dependent kinase 5; dopamine; globus pallidus; glutamate; medium spiny neurons; myocyte enhancer factor 2; nucleus accumbens; postsynaptic densities; retrorubral area; striatum; substantia nigra; substantia nigra pars compacta; substantia nigra pars reticulata; subthalamic nucleus; synaptic cell adhesion molecule 1; thalamostriatal; vGluT1; vGluT2; ventral tegmental area; vesicular glutamate transporter 1; vesicular glutamate transporter 2

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