Plastic changes at corticostriatal synapses predict improved motor function in a partial lesion model of Parkinson’s disease

Bentea, Eduard; Moore, Cynthia; Deneyer, Lauren; Verbruggen, Lise; Churchill, Madeline J.; Hood, Rebecca L.; Meshul, Charles K.; Massie, Ann

doi:10.1016/j.brainresbull.2017.02.005

Cited by 10 publications

(9 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aberrant synaptic function contributes to the synaptic deficits and is associated with the pathological process of neurodegenerative disorders and also the changes in synaptic activity occur prior to the pathological changes in neurons. 17 Thus, the changes in astrocytes condition can influence the information processing at synapses. It has been reported that PQ exerted the effect on synaptic growth and development of neurons through autophagy.…”

Section: Introductionmentioning

confidence: 99%

Detrimental Effects of Paraquat on Astrocytes-Regulating Synaptic Functions

Zheng²,

Zhang

2018

Dose-Response

View full text Add to dashboard Cite

Paraquat (PQ) exposure is known as a risk factor for developing neurodegenerative diseases. Astrocytes are implicated and affected in neurodegenerative diseases and brain injuries, so it is suspected that PQ may impose detrimental effects on astrocytes function. Here, we present a study of the effects of PQ on synaptic function of astrocytes. Human astrocytes (HA1800) were separately treated with PQ at 200, 400, and 800 µmol/L for 12, 24, and 48 hours, respectively. The concentrations of membrane cholesterol, intracellular glutamate, and adenosine triphosphate (ATP) were assessed by measuring changes with Kits after PQ treatment. Expression levels of glial fibrillary acidic protein (GFAP) and apolipoprotein E (ApoE) were detected using Western blot method. The results indicated that astrocytes were highly susceptible to PQ showing astrogliosis characterized by enhanced GFAP expression (P < .05). The decreased cholesterol level and ApoE expression were observed in PQ-treated astrocytes and so were the decreased levels of glutamates and ATP in PQ-treated astrocytes. These results suggested that PQ exerted the detrimental effects on synaptic function of astrocytes, which may be involved in the progressive process of neurodegenerative disorders.

show abstract

Section: Introductionmentioning

confidence: 99%

Detrimental Effects of Paraquat on Astrocytes-Regulating Synaptic Functions

Zheng²,

Zhang

2018

Dose-Response

View full text Add to dashboard Cite

show abstract

“…used an animal model of partial dopaminergic depletion that replicates early stages of PD and verified that the reorganization of the glutamatergic corticostriatal pathway was associated with improvement in the motor function of the animals (Bentea et al . ). In addition, Charron et al .…”

Section: Discussionmentioning

confidence: 97%

α‐synuclein oligomers enhance astrocyte‐induced synapse formation through TGF‐β1 signaling in a Parkinson's disease model

Diniz

Matias

Araújo

et al. 2019

Journal of Neurochemistry

View full text Add to dashboard Cite

Parkinson's disease (PD) is characterized by selective death of dopaminergic neurons in the substantia nigra, degeneration of the nigrostriatal pathway, increases in glutamatergic synapses in the striatum and aggregation of α‐synuclein. Evidence suggests that oligomeric species of α‐synuclein (αSO) are the genuine neurotoxins of PD. Although several studies have supported the direct neurotoxic effects of αSO on neurons, their effects on astrocytes have not been directly addressed. Astrocytes are essential to several steps of synapse formation and function, including secretion of synaptogenic factors, control of synaptic elimination and stabilization, secretion of neural/glial modulators, and modulation of extracellular ions, and neurotransmitter levels in the synaptic cleft. Here, we show that αSO induced the astrocyte reactivity and enhanced the synaptogenic capacity of human and murine astrocytes by increasing the levels of the known synaptogenic molecule transforming growth factor beta 1 (TGF‐β1). Moreover, intracerebroventricular injection of αSO in mice increased the number of astrocytes, the density of excitatory synapses, and the levels of TGF‐β1 in the striatum of injected animals. Inhibition of TGF‐β1 signaling impaired the effect of the astrocyte‐conditioned medium on glutamatergic synapse formation in vitro and on striatal synapse formation in vivo, whereas addition of TGF‐β1 protected mesencephalic neurons against synapse loss triggered by αSO. Together, our data suggest that αSO have important effects on astrocytic functions and describe TGF‐β1 as a new endogenous astrocyte‐derived molecule involved in the increase in striatal glutamatergic synaptic density present in early stages of PD. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: .

show abstract

“…In the DA-denervated model of PD, morphological ndings showed that spine density is signi cantly reduced in striatal MSNs [40]. However, in the partial PD model induced with lactacystin, an insigni cant change in the density of postsynaptic spine was seen, while a signi cant increase in both the length and area of postsynaptic density occurred at corticostriatal synapses [14]. Similarly, we observed a slight but not signi cant reduction in the density of postsynaptic spines in the partial-lesioned 6-OHDA model.…”

Section: Discussionmentioning

confidence: 98%

“…Meanwhile, a moderate DA depletion (70%) was found in the striatum of 6-OHDA mice, indicating a partial loss of DA contents in PD mice [7]. In a different partial model generated by intranigral administration of the proteasome inhibitor lactacystin, a moderate impairment of motor coordination occurred in the rotarod performance [14]. In addition, unilateral injection of 6-OHDA into the MFB at a low dose (3 µg) caused mild motor de cits, including forelimb akinesia in the stepping test [8].…”

Section: Discussionmentioning

confidence: 99%

“…Loss of dopaminergic innervation in the striatum leads to the de cits in motor skills and triggers aberrant striatal synaptic plasticity [7,[10][11][12][13]. DA depletion at different extents have been shown to differentially affect striatal synaptic plasticity, subsequently leading to PD motor symptoms of various severity [7,14,15]. A complete DA denervation triggers maladaptive synaptic plasticity including loss of both long-term potentiation (LTP) and long-term depression (LTD) at corticostriatal synapses [7,16,17] and induces severe motor behaviors.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Electro-acupuncture alleviates motor deficits and maladaptive striatal plasticity in partial-lesioned parkinsonian mice

Su¹,

Yu²,

Li³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Parkinson's disease is characterized by abnormal synaptic transmission in the corticostriatal circuit that leads to deficits in motor abilities. Electro-acupuncture has shown to improve the motor behaviors in parkinsonian models. However, the potential mechanisms underlying the electro-acupuncture treatment, specifically in the partial-lesioned model, remain unclear. Methods By utilizing multiple approaches, including electrophysiological, immunohistochemistrical, molecular and behavioral methods, we assessed the effect of electro-acupuncture on the motor dysfunction and striatal synaptic plasticity in a partial-lesioned mouse model induced by intrastriatal injection of 6-hydroxydopamine. Results Electro-acupuncture ameliorated the disrupted gross and fine motor skills in 6-hydroxydopamine-lesioned mice. Notably, electro-acupuncture not only restored the injured corticostriatal long-term potentiation, but also reversed the loss of GluN1-containing NMDA receptors and GluA1-containing AMPA receptors in the striatum. Furthermore, the antagonists selective for AMPA receptors and NMDA receptors blocked the effect of electro-acupuncture on the corticostriatal long-term potentiation in 6-hydroxydopamine-treated mice. Conclusions These data suggest that the postsynaptic glutamate receptors in the striatum undergo the maladaptive changes in the early stage of Parkinson's disease. Electro-acupuncture improves the motor skills via a mechanism involving the modulation of corticostriatal synaptic plasticity and specific glutamate receptors in a partial-lesioned rodent model.

show abstract

Plastic changes at corticostriatal synapses predict improved motor function in a partial lesion model of Parkinson’s disease

Cited by 10 publications

References 49 publications

Detrimental Effects of Paraquat on Astrocytes-Regulating Synaptic Functions

Detrimental Effects of Paraquat on Astrocytes-Regulating Synaptic Functions

α‐synuclein oligomers enhance astrocyte‐induced synapse formation through TGF‐β1 signaling in a Parkinson's disease model

Electro-acupuncture alleviates motor deficits and maladaptive striatal plasticity in partial-lesioned parkinsonian mice

Contact Info

Product

Resources

About