Interactions Between Epilepsy and Plasticity

Jarero-Basulto, Jose J.; Gasca-Martínez, Yadira; Rivera-Cervantes, M.C.; Ureña‐Guerrero, Mónica E.; Feria‐Velasco, Alfredo; Beas‐Zárate, Carlos

doi:10.3390/ph11010017

Cited by 47 publications

(37 citation statements)

References 175 publications

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“…The filopodia-like spines are presumably prone to support initiation of synaptic plasticity processes [4, 36, 50]. Therefore, this result may suggest that DG may undergo synaptic plasticity that may predispose this brain structure to support epileptogenesis that is a frequent consequence of TBI [56, 57].…”

Section: Discussionmentioning

confidence: 99%

MMP-9 Contributes to Dendritic Spine Remodeling Following Traumatic Brain Injury

2019

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Traumatic brain injury (TBI) occurs when a blow to the head causes brain damage. Apart from physical trauma, it causes a wide range of cognitive, behavioral, and emotional deficits including impairments in learning and memory. On neuronal level, TBI may lead to circuitry remodeling and in effect imbalance between excitatory and inhibitory neurotransmissions. Such change in brain homeostasis may often lead to brain disorders. The basic units of neuronal connectivity are dendritic spines that are tiny protrusions forming synapses between two cells in a network. Spines are dynamic structures that undergo morphological transformation throughout life. Their shape is strictly related to an on/off state of synapse and the strength of synaptic transmission. Matrix metalloproteinase-9 (MMP-9) is an extrasynaptically operating enzyme that plays a role in spine remodeling and has been reported to be activated upon TBI. The aim of the present study was to evaluate the influence of MMP-9 on dendritic spine density and morphology following controlled cortical impact (CCI) as animal model of TBI. We examined spine density and dendritic spine shape in the cerebral cortex and the hippocampus. CCI caused a marked decrease in spine density as well as spine shrinkage in the cerebral cortex ipsilateral to the injury, when compared to sham animals and contralateral side both 1 day and 1 week after the insult. Decreased spine density was also observed in the dentate gyrus of the hippocampus; however, in contrast to the cerebral cortex, spines in the DG became more filopodia-like. In mice lacking MMP-9, no effects of TBI on spine density and morphology were observed.

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Section: Discussionmentioning

confidence: 99%

MMP-9 Contributes to Dendritic Spine Remodeling Following Traumatic Brain Injury

2019

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“…In particular, since PNNs are thought to inhibit synaptic plasticity [14, 17], the decrease in PV-positive neurons not surrounded by PNNs observed in this study indicates a decrease in plasticity in the hippocampus of mice after kindling acquisition. It has long been known that changes to synaptic plasticity are associated with epileptogenesis [6, 7]. For instance, neural circuits that maintain high excitability are caused by changes in synaptic plasticity due to repetitive stimulation in patients with epilepsy and experimental animal models of epilepsy [60–62].…”

Section: Discussionmentioning

confidence: 99%

“…Although seizures can induce neuronal death, they also have nonfatal pathophysiological effects on neuronal structure and function [5]. For example, epileptogenesis is associated with changes to synaptic plasticity [6, 7]. However, what causes and maintains these changes has not been clarified.…”

Section: Introductionmentioning

confidence: 99%

Alteration of Extracellular Matrix Molecules and Perineuronal Nets in the Hippocampus of Pentylenetetrazol-Kindled Mice

et al. 2019

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The pathophysiological processes leading to epilepsy are poorly understood. Understanding the molecular and cellular mechanisms involved in the onset of epilepsy is crucial for drug development. Epileptogenicity is thought to be associated with changes in synaptic plasticity; however, whether extracellular matrix molecules—known regulators of synaptic plasticity—are altered during epileptogenesis is unknown. To test this, we used a pentylenetetrazole- (PTZ-) kindling model mouse to investigate changes to hippocampal parvalbumin- (PV-) positive neurons, extracellular matrix molecules, and perineuronal nets (PNNs) after the last kindled seizure. We found an increase in Wisteria floribunda agglutinin- (WFA-) and Cat-315-positive PNNs and a decrease in PV-positive neurons not surrounded by PNNs, in the hippocampus of PTZ-kindled mice compared to control mice. Furthermore, the expression of WFA- and Cat-315-positive molecules increased in the extracellular space of PTZ-kindled mice. In addition, consistent with previous studies, astrocytes were activated in PTZ-kindled mice. We propose that the increase in PNNs after kindling decreases neuroplasticity in the hippocampus and helps maintain the neural circuit for recurrent seizures. This study shows that possibility of changes in extracellular matrix molecules due to astrocyte activation is associated with epilepticus in PTZ-kindled mice.

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“…The molecular mechanisms underlying kindling and the development of abnormal excitability in epilepsy are poorly understood. Studies have shown that changes in synaptic plasticity lead to epilepsy ( Scharfman et al, 2002 ; Jarero-Basulto JJ et al, 2018 ). We have shown in previous studies that activation of astrocytes in the PTZ-induced kindling model may lead to increased ECM secretion ( Ueno et al, 2019a , 2019b ).…”

Section: Introductionmentioning

confidence: 99%

Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy

et al. 2020

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Understanding the molecular and cellular mechanisms involved during the onset of epilepsy is crucial for elucidating the overall mechanism of epileptogenesis and therapeutic strategies. Previous studies, using a pentylenetetrazole (PTZ)-induced kindling mouse model, showed that astrocyte activation and an increase in perineuronal nets (PNNs) and extracellular matrix (ECM) molecules occurred within the hippocampus. However, the mechanisms of initiation and suppression of these changes, remain unclear. Herein, we analyzed the attenuation of astrocyte activation caused by dizocilpine (MK-801) administration, as well as the anticonvulsant effect of α-pinene on seizures and production of ECM molecules. Our results showed that MK-801 significantly reduced kindling acquisition, while α-pinene treatment prevented an increase in seizures incidences. Both MK-801 and α-pinene administration attenuated astrocyte activation by PTZ and significantly attenuated the increase in ECM molecules. Our results indicate that astrocyte activation and an increase in ECM may contribute to epileptogenesis and suggest that MK-801 and α-pinene may prevent epileptic seizures by suppressing astrocyte activation and ECM molecule production.

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Interactions Between Epilepsy and Plasticity

Cited by 47 publications

References 175 publications

MMP-9 Contributes to Dendritic Spine Remodeling Following Traumatic Brain Injury

MMP-9 Contributes to Dendritic Spine Remodeling Following Traumatic Brain Injury

Alteration of Extracellular Matrix Molecules and Perineuronal Nets in the Hippocampus of Pentylenetetrazol-Kindled Mice

Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy

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