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Morphological changes of glutamatergic synapses in animal models of Parkinson's disease.

Villalba RM, Mathai A, Smith Y - Front Neuroanat (2015)

Bottom Line: More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys.The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered.Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined.

View Article: PubMed Central - PubMed

Affiliation: Yerkes National Primate Research Center, Emory University Atlanta, GA, USA ; UDALL Center of Excellence for Parkinson's Disease, Emory University Atlanta, GA, USA.

ABSTRACT
The striatum and the subthalamic nucleus (STN) are the main entry doors for extrinsic inputs to reach the basal ganglia (BG) circuitry. The cerebral cortex, thalamus and brainstem are the key sources of glutamatergic inputs to these nuclei. There is anatomical, functional and neurochemical evidence that glutamatergic neurotransmission is altered in the striatum and STN of animal models of Parkinson's disease (PD) and that these changes may contribute to aberrant network neuronal activity in the BG-thalamocortical circuitry. Postmortem studies of animal models and PD patients have revealed significant pathology of glutamatergic synapses, dendritic spines and microcircuits in the striatum of parkinsonians. More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys. In this review, we will discuss evidence for synaptic glutamatergic dysfunction and pathology of cortical and thalamic inputs to the striatum and STN in models of PD. The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered. Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined.

No MeSH data available.


Related in: MedlinePlus

Dendritic spines in the monkey striatum. (A,B) Light micrographs of dendrites from Golgi-impregnated medium spiny neurons (MSNs) in the caudate nucleus of a control (A) and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated (B) monkey. Note the dramatic spine loss of the dendrite of the MSN from the MPTP-treated monkey compared with control. (C1–D2) Three-dimension (3D)-reconstructed images of glutamatergic axo-spinous synapses from control (C1,C2) and MPTP-treated (D1,D2) monkeys. (E) Histogram comparing the morphometric measurements (mean ± SEM) for spine volume (μm3), post-synaptic density (PSD) area (μm2) and terminal volume (μm3) of structural elements at corticostriatal (vGluT1-positive) glutamatergic synapses using 3D reconstruction method of serial ultrathin sections collected from 30 axo-spinous synapses in each group from three control and three MPTP-treated animals. The spine volumes, the PSD areas, and the volume of vGluT1-containing terminals are significantly larger in MPTP-treated parkinsonian monkeys than in controls (*t-test; p < 0.001). Scale bar in (B) (applied to A) = 5 μm (See Villalba et al., 2009; Villalba and Smith, 2010, 2011a, 2013).
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Figure 1: Dendritic spines in the monkey striatum. (A,B) Light micrographs of dendrites from Golgi-impregnated medium spiny neurons (MSNs) in the caudate nucleus of a control (A) and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated (B) monkey. Note the dramatic spine loss of the dendrite of the MSN from the MPTP-treated monkey compared with control. (C1–D2) Three-dimension (3D)-reconstructed images of glutamatergic axo-spinous synapses from control (C1,C2) and MPTP-treated (D1,D2) monkeys. (E) Histogram comparing the morphometric measurements (mean ± SEM) for spine volume (μm3), post-synaptic density (PSD) area (μm2) and terminal volume (μm3) of structural elements at corticostriatal (vGluT1-positive) glutamatergic synapses using 3D reconstruction method of serial ultrathin sections collected from 30 axo-spinous synapses in each group from three control and three MPTP-treated animals. The spine volumes, the PSD areas, and the volume of vGluT1-containing terminals are significantly larger in MPTP-treated parkinsonian monkeys than in controls (*t-test; p < 0.001). Scale bar in (B) (applied to A) = 5 μm (See Villalba et al., 2009; Villalba and Smith, 2010, 2011a, 2013).

Mentions: Striatal spine loss has been reported in the striatum of various animal models of PD and in parkinsonian patients. In both MPTP-treated monkeys and PD patients, the extent of spine pruning is tightly correlated with the extent of striatal dopaminergic denervation (Ingham et al., 1989; Stephens et al., 2005; Zaja-Milatovic et al., 2005; Smith and Villalba, 2008; Smith et al., 2009b; Villalba et al., 2009; Toy et al., 2014; Figures 1A,B, 4).


Morphological changes of glutamatergic synapses in animal models of Parkinson's disease.

Villalba RM, Mathai A, Smith Y - Front Neuroanat (2015)

Dendritic spines in the monkey striatum. (A,B) Light micrographs of dendrites from Golgi-impregnated medium spiny neurons (MSNs) in the caudate nucleus of a control (A) and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated (B) monkey. Note the dramatic spine loss of the dendrite of the MSN from the MPTP-treated monkey compared with control. (C1–D2) Three-dimension (3D)-reconstructed images of glutamatergic axo-spinous synapses from control (C1,C2) and MPTP-treated (D1,D2) monkeys. (E) Histogram comparing the morphometric measurements (mean ± SEM) for spine volume (μm3), post-synaptic density (PSD) area (μm2) and terminal volume (μm3) of structural elements at corticostriatal (vGluT1-positive) glutamatergic synapses using 3D reconstruction method of serial ultrathin sections collected from 30 axo-spinous synapses in each group from three control and three MPTP-treated animals. The spine volumes, the PSD areas, and the volume of vGluT1-containing terminals are significantly larger in MPTP-treated parkinsonian monkeys than in controls (*t-test; p < 0.001). Scale bar in (B) (applied to A) = 5 μm (See Villalba et al., 2009; Villalba and Smith, 2010, 2011a, 2013).
© Copyright Policy
Related In: Results  -  Collection

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Figure 1: Dendritic spines in the monkey striatum. (A,B) Light micrographs of dendrites from Golgi-impregnated medium spiny neurons (MSNs) in the caudate nucleus of a control (A) and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated (B) monkey. Note the dramatic spine loss of the dendrite of the MSN from the MPTP-treated monkey compared with control. (C1–D2) Three-dimension (3D)-reconstructed images of glutamatergic axo-spinous synapses from control (C1,C2) and MPTP-treated (D1,D2) monkeys. (E) Histogram comparing the morphometric measurements (mean ± SEM) for spine volume (μm3), post-synaptic density (PSD) area (μm2) and terminal volume (μm3) of structural elements at corticostriatal (vGluT1-positive) glutamatergic synapses using 3D reconstruction method of serial ultrathin sections collected from 30 axo-spinous synapses in each group from three control and three MPTP-treated animals. The spine volumes, the PSD areas, and the volume of vGluT1-containing terminals are significantly larger in MPTP-treated parkinsonian monkeys than in controls (*t-test; p < 0.001). Scale bar in (B) (applied to A) = 5 μm (See Villalba et al., 2009; Villalba and Smith, 2010, 2011a, 2013).
Mentions: Striatal spine loss has been reported in the striatum of various animal models of PD and in parkinsonian patients. In both MPTP-treated monkeys and PD patients, the extent of spine pruning is tightly correlated with the extent of striatal dopaminergic denervation (Ingham et al., 1989; Stephens et al., 2005; Zaja-Milatovic et al., 2005; Smith and Villalba, 2008; Smith et al., 2009b; Villalba et al., 2009; Toy et al., 2014; Figures 1A,B, 4).

Bottom Line: More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys.The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered.Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined.

View Article: PubMed Central - PubMed

Affiliation: Yerkes National Primate Research Center, Emory University Atlanta, GA, USA ; UDALL Center of Excellence for Parkinson's Disease, Emory University Atlanta, GA, USA.

ABSTRACT
The striatum and the subthalamic nucleus (STN) are the main entry doors for extrinsic inputs to reach the basal ganglia (BG) circuitry. The cerebral cortex, thalamus and brainstem are the key sources of glutamatergic inputs to these nuclei. There is anatomical, functional and neurochemical evidence that glutamatergic neurotransmission is altered in the striatum and STN of animal models of Parkinson's disease (PD) and that these changes may contribute to aberrant network neuronal activity in the BG-thalamocortical circuitry. Postmortem studies of animal models and PD patients have revealed significant pathology of glutamatergic synapses, dendritic spines and microcircuits in the striatum of parkinsonians. More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys. In this review, we will discuss evidence for synaptic glutamatergic dysfunction and pathology of cortical and thalamic inputs to the striatum and STN in models of PD. The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered. Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined.

No MeSH data available.


Related in: MedlinePlus