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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

vGluT1-positive innervation in the monkey subthalamic nucleus (STN). (A) Light micrograph showing vGluT1-positive varicose processes. (B) Average density (mean ± SEM; N = 3) of vGluT1-immunoreactive varicosities in the dorsolateral STN of normal and parkinsonian monkeys (*, t-test, p = 0.012). (C) Comparison of the average STN volume (mean ± SEM; N = 3) between normal and parkinsonian monkeys. (D) Electron micrograph showing an asymmetric synapse (arrows) in the dorsolateral monkey STN. (E) Average density (mean ± SEM; N = 3) of vGluT1-immunopositive terminals in the dorsolateral STN of normal and parkinsonian monkeys (*, t-test, p = 0.02). (F) Average density (mean ± SEM; N = 3) of asymmetric synapses in the dorsolateral STN of normal and pakinsonian monkeys (*, t-test, p = 0.029). (G,H) Electron micrographs showing vGluT1-containing terminals forming asymmetric synapses with a spine (G) and a dendritic shaft (H). (I) Post-synaptic targets of vGluT1-immunopositive terminals in the dorsolateral STN. No differences were found in the proportion of vGluT1-immunoreactive terminals forming asymmetric synapses with dendritic shafts and spines in normal and parkinsonian animals. Scale bar A = 10 μm and in (D; applies also to G) and H = 0.2 μm. Abbreviations: Den, dendrite; Sp, dendritic spine; T, axon terminal (See Mathai et al., 2015).
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Figure 3: vGluT1-positive innervation in the monkey subthalamic nucleus (STN). (A) Light micrograph showing vGluT1-positive varicose processes. (B) Average density (mean ± SEM; N = 3) of vGluT1-immunoreactive varicosities in the dorsolateral STN of normal and parkinsonian monkeys (*, t-test, p = 0.012). (C) Comparison of the average STN volume (mean ± SEM; N = 3) between normal and parkinsonian monkeys. (D) Electron micrograph showing an asymmetric synapse (arrows) in the dorsolateral monkey STN. (E) Average density (mean ± SEM; N = 3) of vGluT1-immunopositive terminals in the dorsolateral STN of normal and parkinsonian monkeys (*, t-test, p = 0.02). (F) Average density (mean ± SEM; N = 3) of asymmetric synapses in the dorsolateral STN of normal and pakinsonian monkeys (*, t-test, p = 0.029). (G,H) Electron micrographs showing vGluT1-containing terminals forming asymmetric synapses with a spine (G) and a dendritic shaft (H). (I) Post-synaptic targets of vGluT1-immunopositive terminals in the dorsolateral STN. No differences were found in the proportion of vGluT1-immunoreactive terminals forming asymmetric synapses with dendritic shafts and spines in normal and parkinsonian animals. Scale bar A = 10 μm and in (D; applies also to G) and H = 0.2 μm. Abbreviations: Den, dendrite; Sp, dendritic spine; T, axon terminal (See Mathai et al., 2015).

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)

vGluT1-positive innervation in the monkey subthalamic nucleus (STN). (A) Light micrograph showing vGluT1-positive varicose processes. (B) Average density (mean ± SEM; N = 3) of vGluT1-immunoreactive varicosities in the dorsolateral STN of normal and parkinsonian monkeys (*, t-test, p = 0.012). (C) Comparison of the average STN volume (mean ± SEM; N = 3) between normal and parkinsonian monkeys. (D) Electron micrograph showing an asymmetric synapse (arrows) in the dorsolateral monkey STN. (E) Average density (mean ± SEM; N = 3) of vGluT1-immunopositive terminals in the dorsolateral STN of normal and parkinsonian monkeys (*, t-test, p = 0.02). (F) Average density (mean ± SEM; N = 3) of asymmetric synapses in the dorsolateral STN of normal and pakinsonian monkeys (*, t-test, p = 0.029). (G,H) Electron micrographs showing vGluT1-containing terminals forming asymmetric synapses with a spine (G) and a dendritic shaft (H). (I) Post-synaptic targets of vGluT1-immunopositive terminals in the dorsolateral STN. No differences were found in the proportion of vGluT1-immunoreactive terminals forming asymmetric synapses with dendritic shafts and spines in normal and parkinsonian animals. Scale bar A = 10 μm and in (D; applies also to G) and H = 0.2 μm. Abbreviations: Den, dendrite; Sp, dendritic spine; T, axon terminal (See Mathai et al., 2015).
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Related In: Results  -  Collection

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Figure 3: vGluT1-positive innervation in the monkey subthalamic nucleus (STN). (A) Light micrograph showing vGluT1-positive varicose processes. (B) Average density (mean ± SEM; N = 3) of vGluT1-immunoreactive varicosities in the dorsolateral STN of normal and parkinsonian monkeys (*, t-test, p = 0.012). (C) Comparison of the average STN volume (mean ± SEM; N = 3) between normal and parkinsonian monkeys. (D) Electron micrograph showing an asymmetric synapse (arrows) in the dorsolateral monkey STN. (E) Average density (mean ± SEM; N = 3) of vGluT1-immunopositive terminals in the dorsolateral STN of normal and parkinsonian monkeys (*, t-test, p = 0.02). (F) Average density (mean ± SEM; N = 3) of asymmetric synapses in the dorsolateral STN of normal and pakinsonian monkeys (*, t-test, p = 0.029). (G,H) Electron micrographs showing vGluT1-containing terminals forming asymmetric synapses with a spine (G) and a dendritic shaft (H). (I) Post-synaptic targets of vGluT1-immunopositive terminals in the dorsolateral STN. No differences were found in the proportion of vGluT1-immunoreactive terminals forming asymmetric synapses with dendritic shafts and spines in normal and parkinsonian animals. Scale bar A = 10 μm and in (D; applies also to G) and H = 0.2 μm. Abbreviations: Den, dendrite; Sp, dendritic spine; T, axon terminal (See Mathai et al., 2015).
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