Abstract
Striatal dopamine denervation is the pathological hallmark of Parkinson's disease (PD). Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba and Smith, 2011). The concept of tripartite synapses (TS) was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a). Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia–neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD therapeutics.
Highlights
One of the main neuropathological features of Parkinson’s disease (PD) is the degeneration of the nigrostriatal dopaminergic pathway, which induces complex physiological changes within the basal ganglia circuitry, including profound alterations in the activity of the corticostriatal glutamatergic system (Calabresi et al, 1996, 2007; Mallet et al, 2006; Wichmann and Delong, 2007)
A major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on striatal medium spiny projection neurons (Ingham et al, 1989; Stephens et al, 2005; Zaja-Milatovic et al, 2005; Day et al, 2006; Deutch et al, 2007; Villalba et al, 2009)
The increased corticostriatal functions described in MPTPtreated monkeys (Cao et al, 2010) could be the result of a compensatory overactivity of corticostriatal glutamatergic terminals supported by ultrastructural plastic changes described in this and our previous study (Villalba and Smith, 2011)
Summary
We discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia–neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD therapeutics
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