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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

Tripartite synapses (TS) in the monkey striatum. (A,D) Electron micrographs of perisynaptic astrocytic processes (Ast) wrapping a vGluT1 axo-spinous synapse in control (A) and MPTP-treated (D) animal. (B,C,E,F) The three-dimensional (3D) reconstruction of a vGluT1-immunoreactive TS highlight the differences in the extensions of the astrocytic processes between control (B,C) and MPTP (E,F). In the TS of control animals, the perimeters of the axon-spinous interfaces were only partially surrounded by astroglial processes (B,C). In MPTP-treated animals, TS vGluT1-containing synapses displayed a large increase in astroglial processes ensheatment (E,F). (G) Histograms comparing the surface area of perisynaptic glia associated with vGluT1- and vGluT2-immunopositive axo-spinous synapses in control (N = 3) and MPTP-treated (N = 3) monkeys (mean ± SEM). The surface of the perisynaptic glia was significant larger (*, t-test, p = 0.017 for vGluT1 and p = 0.006 for vGluT2) in MPTP-parkinsonian monkeys than in control. (H) Histograms comparing the ratio of the volume of the perisynaptic glia over the total volume of spine and the axon terminals in TS formed by vGluT1- or vGluT2-immunoreactive terminals. This ratio was significantly larger in MPTP than in control condition (*, t-test, p = 0.049 for vGluT1 and p = 0.028 for vGluT2). No significant difference was found between TS formed by vGluT1- or vGluT2-immunoreactive terminals. Total number of reconstructed spines = 32 (8 per group). Statistics were performed by using SigmaPlot (version 11.0). Abbreviations: Ast, astrocyte; PSD, post-synaptic density; Sp, dendritic spine; T, axon terminal (see Villalba and Smith, 2011b for details).
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Figure 2: Tripartite synapses (TS) in the monkey striatum. (A,D) Electron micrographs of perisynaptic astrocytic processes (Ast) wrapping a vGluT1 axo-spinous synapse in control (A) and MPTP-treated (D) animal. (B,C,E,F) The three-dimensional (3D) reconstruction of a vGluT1-immunoreactive TS highlight the differences in the extensions of the astrocytic processes between control (B,C) and MPTP (E,F). In the TS of control animals, the perimeters of the axon-spinous interfaces were only partially surrounded by astroglial processes (B,C). In MPTP-treated animals, TS vGluT1-containing synapses displayed a large increase in astroglial processes ensheatment (E,F). (G) Histograms comparing the surface area of perisynaptic glia associated with vGluT1- and vGluT2-immunopositive axo-spinous synapses in control (N = 3) and MPTP-treated (N = 3) monkeys (mean ± SEM). The surface of the perisynaptic glia was significant larger (*, t-test, p = 0.017 for vGluT1 and p = 0.006 for vGluT2) in MPTP-parkinsonian monkeys than in control. (H) Histograms comparing the ratio of the volume of the perisynaptic glia over the total volume of spine and the axon terminals in TS formed by vGluT1- or vGluT2-immunoreactive terminals. This ratio was significantly larger in MPTP than in control condition (*, t-test, p = 0.049 for vGluT1 and p = 0.028 for vGluT2). No significant difference was found between TS formed by vGluT1- or vGluT2-immunoreactive terminals. Total number of reconstructed spines = 32 (8 per group). Statistics were performed by using SigmaPlot (version 11.0). Abbreviations: Ast, astrocyte; PSD, post-synaptic density; Sp, dendritic spine; T, axon terminal (see Villalba and Smith, 2011b for details).

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)

Tripartite synapses (TS) in the monkey striatum. (A,D) Electron micrographs of perisynaptic astrocytic processes (Ast) wrapping a vGluT1 axo-spinous synapse in control (A) and MPTP-treated (D) animal. (B,C,E,F) The three-dimensional (3D) reconstruction of a vGluT1-immunoreactive TS highlight the differences in the extensions of the astrocytic processes between control (B,C) and MPTP (E,F). In the TS of control animals, the perimeters of the axon-spinous interfaces were only partially surrounded by astroglial processes (B,C). In MPTP-treated animals, TS vGluT1-containing synapses displayed a large increase in astroglial processes ensheatment (E,F). (G) Histograms comparing the surface area of perisynaptic glia associated with vGluT1- and vGluT2-immunopositive axo-spinous synapses in control (N = 3) and MPTP-treated (N = 3) monkeys (mean ± SEM). The surface of the perisynaptic glia was significant larger (*, t-test, p = 0.017 for vGluT1 and p = 0.006 for vGluT2) in MPTP-parkinsonian monkeys than in control. (H) Histograms comparing the ratio of the volume of the perisynaptic glia over the total volume of spine and the axon terminals in TS formed by vGluT1- or vGluT2-immunoreactive terminals. This ratio was significantly larger in MPTP than in control condition (*, t-test, p = 0.049 for vGluT1 and p = 0.028 for vGluT2). No significant difference was found between TS formed by vGluT1- or vGluT2-immunoreactive terminals. Total number of reconstructed spines = 32 (8 per group). Statistics were performed by using SigmaPlot (version 11.0). Abbreviations: Ast, astrocyte; PSD, post-synaptic density; Sp, dendritic spine; T, axon terminal (see Villalba and Smith, 2011b for details).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585113&req=5

Figure 2: Tripartite synapses (TS) in the monkey striatum. (A,D) Electron micrographs of perisynaptic astrocytic processes (Ast) wrapping a vGluT1 axo-spinous synapse in control (A) and MPTP-treated (D) animal. (B,C,E,F) The three-dimensional (3D) reconstruction of a vGluT1-immunoreactive TS highlight the differences in the extensions of the astrocytic processes between control (B,C) and MPTP (E,F). In the TS of control animals, the perimeters of the axon-spinous interfaces were only partially surrounded by astroglial processes (B,C). In MPTP-treated animals, TS vGluT1-containing synapses displayed a large increase in astroglial processes ensheatment (E,F). (G) Histograms comparing the surface area of perisynaptic glia associated with vGluT1- and vGluT2-immunopositive axo-spinous synapses in control (N = 3) and MPTP-treated (N = 3) monkeys (mean ± SEM). The surface of the perisynaptic glia was significant larger (*, t-test, p = 0.017 for vGluT1 and p = 0.006 for vGluT2) in MPTP-parkinsonian monkeys than in control. (H) Histograms comparing the ratio of the volume of the perisynaptic glia over the total volume of spine and the axon terminals in TS formed by vGluT1- or vGluT2-immunoreactive terminals. This ratio was significantly larger in MPTP than in control condition (*, t-test, p = 0.049 for vGluT1 and p = 0.028 for vGluT2). No significant difference was found between TS formed by vGluT1- or vGluT2-immunoreactive terminals. Total number of reconstructed spines = 32 (8 per group). Statistics were performed by using SigmaPlot (version 11.0). Abbreviations: Ast, astrocyte; PSD, post-synaptic density; Sp, dendritic spine; T, axon terminal (see Villalba and Smith, 2011b for details).
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