scholarly journals Modeling Resilience to Damage in Multiple Sclerosis: Plasticity Meets Connectivity

2019 ◽  
Vol 21 (1) ◽  
pp. 143 ◽  
Author(s):  
Mario Stampanoni Bassi ◽  
Ennio Iezzi ◽  
Luigi Pavone ◽  
Georgia Mandolesi ◽  
Alessandra Musella ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Synaptic Plasticity ◽  
Network Architecture ◽  
White Matter Lesions ◽  
Long Term Potentiation ◽  
Chronic Inflammatory Disease ◽  
Brain Network ◽  
Term Potentiation ◽  
The Central Nervous System ◽  
Efficient Information

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelinating white matter lesions and neurodegeneration, with a variable clinical course. Brain network architecture provides efficient information processing and resilience to damage. The peculiar organization characterized by a low number of highly connected nodes (hubs) confers high resistance to random damage. Anti-homeostatic synaptic plasticity, in particular long-term potentiation (LTP), represents one of the main physiological mechanisms underlying clinical recovery after brain damage. Different types of synaptic plasticity, including both anti-homeostatic and homeostatic mechanisms (synaptic scaling), contribute to shape brain networks. In MS, altered synaptic functioning induced by inflammatory mediators may represent a further cause of brain network collapse in addition to demyelination and grey matter atrophy. We propose that impaired LTP expression and pathologically enhanced upscaling may contribute to disrupting brain network topology in MS, weakening resilience to damage and negatively influencing the disease course.

Oral D-Aspartate enhances synaptic plasticity reserve in progressive multiple sclerosis

2019 ◽  
Vol 26 (3) ◽  
pp. 304-311 ◽  
Author(s):  
Carolina G Nicoletti ◽  
Fabrizia Monteleone ◽  
Girolama A Marfia ◽  
Alessandro Usiello ◽  
Fabio Buttari ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Synaptic Plasticity ◽  
Cortical Excitability ◽  
Short Interval ◽  
Oral Intake ◽  
Long Term Potentiation ◽  
Progressive Multiple Sclerosis ◽  
Clinical Effects ◽  
Term Potentiation ◽  
Before And After

Background: Synaptic plasticity reserve correlates with clinical recovery after a relapse in relapsing–remitting forms of multiple sclerosis (MS) and is significantly compromised in patients with progressive forms of MS. These findings suggest that progression of disability in MS is linked to reduced synaptic plasticity reserve. D-Aspartate, an endogenous aminoacid approved for the use in humans as a dietary supplement, enhances synaptic plasticity in mice. Objective: To test whether D-Aspartate oral intake increases synaptic plasticity reserve in progressive MS patients. Methods: A total of 31 patients affected by a progressive form of MS received either single oral daily doses of D-Aspartate 2660 mg or placebo for 4 weeks. Synaptic plasticity reserve and trans-synaptic cortical excitability were measured through transcranial magnetic stimulation (TMS) protocols before and after D-Aspartate. Results: Both TMS-induced long-term potentiation (LTP), intracortical facilitation (ICF) and short-interval ICF increased after 2 and 4 weeks of D-Aspartate but not after placebo, suggesting an enhancement of synaptic plasticity reserve and increased trans-synaptic glutamatergic transmission. Conclusion: Daily oral D-Aspartate 2660 mg for 4 weeks enhances synaptic plasticity reserve in patients with progressive MS, opening the path to further studies assessing its clinical effects on disability progression.

Neuronal calcium sensors and synaptic plasticity

2009 ◽  
Vol 37 (6) ◽  
pp. 1359-1363 ◽  
Author(s):  
Mascia Amici ◽  
Andrew Doherty ◽  
Jihoon Jo ◽  
David Jane ◽  
Kwangwook Cho ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Signalling Pathways ◽  
Calcium Sensor ◽  
Calcium Sensors ◽  
Term Potentiation ◽  
Neuronal Calcium Sensor Protein ◽  
The Central Nervous System ◽  
Sensor Proteins

Calcium entry plays a major role in the induction of several forms of synaptic plasticity in different areas of the central nervous system. The spatiotemporal aspects of these calcium signals can determine the type of synaptic plasticity induced, e.g. LTP (long-term potentiation) or LTD (long-term depression). A vast amount of research has been conducted to identify the molecular and cellular signalling pathways underlying LTP and LTD, but many components remain to be identified. Calcium sensor proteins are thought to play an essential role in regulating the initial part of synaptic plasticity signalling pathways. However, there is still a significant gap in knowledge, and it is only recently that evidence for the importance of members of the NCS (neuronal calcium sensor) protein family has started to emerge. The present minireview aims to bring together evidence supporting a role for NCS proteins in plasticity, focusing on emerging roles of NCS-1 and hippocalcin.

Cortical plasticity predicts recovery from relapse in multiple sclerosis

2013 ◽  
Vol 20 (4) ◽  
pp. 451-457 ◽  
Author(s):  
Francesco Mori ◽  
Hajime Kusayanagi ◽  
Carolina Gabri Nicoletti ◽  
Sagit Weiss ◽  
Maria Grazia Marciani ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Synaptic Plasticity ◽  
Cortical Plasticity ◽  
Neuronal Damage ◽  
Complete Recovery ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Relapsing Remitting ◽  
Symptom Recovery ◽  
Relapsing Remitting Multiple Sclerosis

Background: Relapsing–remitting multiple sclerosis (RRMS) is characterized by the occurrence of clinical relapses, followed by remitting phases of a neurological deficit. Clinical remission after a relapse can be complete, with a return to baseline function that was present before, but is sometimes only partial or absent. Remyelination and repair of the neuronal damage do contribute to recovery, but they are usually incomplete. Objective: We tested the hypothesis that synaptic plasticity, namely long-term potentiation (LTP), may represent an additional substrate for compensating the clinical defect that results from the incomplete repair of neuronal damage. Methods: We evaluated the correlation between a measure of LTP, named paired associative stimulation (PAS), at the time of relapse and symptom recovery, in a cohort of 22 newly-diagnosed MS patients. Results: PAS-induced LTP was normal in patients with complete recovery, and reduced in patients showing incomplete or absent recovery, 12 weeks after the relapse onset. A multivariate regression model showed that PAS-induced LTP and age may contribute to predict null, partial or complete symptom recovery after a relapse. Conclusion: Synaptic plasticity may contribute to symptom recovery after a relapse in MS; and PAS, measured during a relapse, may be used as a predictor of recovery.

scholarly journals Simvastatin Impairs Hippocampal Synaptic Plasticity and Cognitive Function in Mice

2021 ◽  
Author(s):  
Yujun Guo ◽  
Guichang Zou ◽  
Keke Qi ◽  
Jin Jin ◽  
Lei Yao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Drug Discontinuation ◽  
Cholesterol Levels ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation ◽  
The Central Nervous System

Abstract Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive

scholarly journals Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yujun Guo ◽  
Guichang Zou ◽  
Keke Qi ◽  
Jin Jin ◽  
Lei Yao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Drug Discontinuation ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation ◽  
The Central Nervous System

AbstractLipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins.

scholarly journals Simvastatin Impairs Hippocampal Synaptic Plasticity and Cognitive Function in Mice

2020 ◽  
Author(s):  
Yujun Guo ◽  
Guichang Zou ◽  
Jin Jin ◽  
Lei Yao ◽  
Keke Qi ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Drug Discontinuation ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation ◽  
The Central Nervous System

Abstract Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins.

scholarly journals Interleukin-1β Alters Hebbian Synaptic Plasticity in Multiple Sclerosis

2020 ◽  
Vol 21 (19) ◽  
pp. 6982 ◽  
Author(s):  
Mario Stampanoni Bassi ◽  
Fabio Buttari ◽  
Carolina Gabri Nicoletti ◽  
Francesco Mori ◽  
Luana Gilio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Synaptic Plasticity ◽  
Hot Spot ◽  
Motor Evoked Potential ◽  
Long Term Potentiation ◽  
Abductor Pollicis Brevis ◽  
Paired Pulse ◽  
Term Potentiation ◽  
Abductor Digiti Minimi ◽  
Intracortical Excitability

In multiple sclerosis (MS), inflammation alters synaptic transmission and plasticity, negatively influencing the disease course. In the present study, we aimed to explore the influence of the proinflammatory cytokine IL-1β on peculiar features of associative Hebbian synaptic plasticity, such as input specificity, using the paired associative stimulation (PAS). In 33 relapsing remitting-MS patients and 15 healthy controls, PAS was performed on the abductor pollicis brevis (APB) muscle. The effects over the motor hot spot of the APB and abductor digiti minimi (ADM) muscles were tested immediately after PAS and 15 and 30 min later. Intracortical excitability was tested with paired-pulse transcranial magnetic stimulation (TMS). The cerebrospinal fluid (CSF) levels of IL-1β were calculated. In MS patients, PAS failed to induce long-term potentiation (LTP)-like effects in the APB muscle and elicited a paradoxical motor-evoked potential (MEP) increase in the ADM. IL-1β levels were negatively correlated with the LTP-like response in the APB muscle. Moreover, IL-1β levels were associated with synaptic hyperexcitability tested with paired-pulse TMS. Synaptic hyperexcitability caused by IL-1β may critically contribute to alter Hebbian plasticity in MS, inducing a loss of topographic specificity.

scholarly journals Synaptic Plasticity Shapes Brain Connectivity: Implications for Network Topology

2019 ◽  
Vol 20 (24) ◽  
pp. 6193 ◽  
Author(s):  
Mario Stampanoni Bassi ◽  
Ennio Iezzi ◽  
Luana Gilio ◽  
Diego Centonze ◽  
Fabio Buttari
Keyword(s):  
Synaptic Plasticity ◽  
Neural Plasticity ◽  
Network Architecture ◽  
Brain Connectivity ◽  
Network Connectivity ◽  
Long Term Potentiation ◽  
Brain Network ◽  
Homeostatic Plasticity ◽  
Network Activity ◽  
Network Organization

Studies of brain network connectivity improved understanding on brain changes and adaptation in response to different pathologies. Synaptic plasticity, the ability of neurons to modify their connections, is involved in brain network remodeling following different types of brain damage (e.g., vascular, neurodegenerative, inflammatory). Although synaptic plasticity mechanisms have been extensively elucidated, how neural plasticity can shape network organization is far from being completely understood. Similarities existing between synaptic plasticity and principles governing brain network organization could be helpful to define brain network properties and reorganization profiles after damage. In this review, we discuss how different forms of synaptic plasticity, including homeostatic and anti-homeostatic mechanisms, could be directly involved in generating specific brain network characteristics. We propose that long-term potentiation could represent the neurophysiological basis for the formation of highly connected nodes (hubs). Conversely, homeostatic plasticity may contribute to stabilize network activity preventing poor and excessive connectivity in the peripheral nodes. In addition, synaptic plasticity dysfunction may drive brain network disruption in neuropsychiatric conditions such as Alzheimer’s disease and schizophrenia. Optimal network architecture, characterized by efficient information processing and resilience, and reorganization after damage strictly depend on the balance between these forms of plasticity.

scholarly journals The Association of Brain-Derived Neurotrophic Factor with Long-Term Potentiation

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Zahra Salimi ◽  
Farshad Moradpour ◽  
Zahra Rashidi ◽  
Fatemeh Zarei ◽  
Mohammad Rasool Khazaei ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Neurotrophic Factor ◽  
Synapse Formation ◽  
Long Term Potentiation ◽  
Brain Derived Neurotrophic Factor ◽  
Synaptic Efficacy ◽  
Term Potentiation ◽  
The Central Nervous System

: Long-term potentiation (LTP) is one of the most important topics in neuroscience. It refers to a long-lasting increase in synaptic efficacy and is considered as a molecular and cellular mechanism of learning and memory. Neurotrophins play essential roles in different processes in the central nervous system (CNS), such as synaptogenesis, survival of specific populations of neurons, and neuroplasticity. Some evidence suggests that neurotrophins also participate in the synaptic plasticity related to learning and memory formation. Brain-derived neurotrophic factor (BDNF) is an important neurotrophic factor that is extensively expressed in the hippocampus and cerebral cortex, where it promotes neuroprotection, increases synaptogenesis and neurotransmission, and mediates synapse formation and synaptic plasticity. In this review, we first focused on the research investigating the effects of BDNF on synaptic plasticity and LTP induction and then reviewed the neuronal signaling molecules employed by BDNF to promote its effects on these processes.

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Yu-Xing Ge ◽  
Ying-Ying Lin ◽  
Qian-Qian Bi ◽  
Yu-Juan Chen
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Synaptic Vesicle ◽  
Long Term Potentiation ◽  
Synaptic Dysfunction ◽  
Over Expression ◽  
Term Potentiation ◽  
Synaptic Vesicle Protein 2A

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

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