scholarly journals Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Dominika Justyna Ksiazek-Winiarek ◽  
Piotr Szpakowski ◽  
Andrzej Glabinski
Keyword(s):  
Multiple Sclerosis ◽  
Neural Plasticity ◽  
Neuronal Plasticity ◽  
Developmental Stages ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Brain Plasticity ◽  
Motor Dysfunction ◽  
Functional Studies ◽  
Repair Mechanisms

Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets.

scholarly journals Mechanisms of neuronal damage in multiple sclerosis and its animal models: role of calcium pumps and exchangers

2007 ◽  
Vol 35 (5) ◽  
pp. 923-926 ◽  
Author(s):  
M.P. Kurnellas ◽  
K.C. Donahue ◽  
S. Elkabes
Keyword(s):  
Multiple Sclerosis ◽  
Animal Models ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Neuronal Function ◽  
Permanent Disability ◽  
Calcium Pumps ◽  
Injury Mechanisms ◽  
The Central Nervous System

Multiple sclerosis is an inflammatory, demyelinating and neurodegenerative disorder of the central nervous system. Increasing evidence indicates that neuronal pathology and axonal injury are early hallmarks of multiple sclerosis and are major contributors to progressive and permanent disability. Yet, the mechanisms underlying neuronal dysfunction and damage are not well defined. Elucidation of such mechanisms is of critical importance for the development of therapeutic strategies that will prevent neurodegeneration and confer neuroprotection. PMCA2 (plasma-membrane Ca2+-ATPase 2) and the NCX (Na+/Ca2+ exchanger) have been implicated in impairment of axonal and neuronal function in multiple sclerosis and its animal models. As PMCA2 and NCX play critical roles in calcium extrusion in cells, alterations in their expression or activity may affect calcium homoeostasis and thereby induce intracellular injury mechanisms. Interventions that restore normal PMCA2 and NCX activity may prevent or slow disease progression by averting neurodegeneration.

Sleep markers in psychiatry: do insomnia and disturbed sleep play as markers of disrupted neuroplasticity in mood disorders? A proposed model

2021 ◽  
Vol 28 ◽  
Author(s):  
Laura Palagini ◽  
Pierre Alexis Geoffroy ◽  
Dieter Riemann
Keyword(s):  
Systematic Review ◽  
Mood Disorders ◽  
Neural Plasticity ◽  
Potential Role ◽  
Neuronal Damage ◽  
Brain Plasticity ◽  
Sleep Loss ◽  
Stress System ◽  
Disturbed Sleep ◽  
Proposed Model

Introduction: Since insomnia and disturbed sleep may affect neuroplasticity, we aimed at reviewing their potential role as markers of disrupted neuroplasticity involved in mood disorders. Method: We performed a systematic review, according to PRIMA, on PubMed, PsycINFO and Embase electronic databases for literature regarding mood disorders, insomnia, sleep loss/deprivation in relation to different pathways involved in the impairment of neuroplasticity in mood disorders such as 1] alterations in neurodevelopment 2] activation of the stress system 3] neuroinflammation 4] neurodegeneration/neuroprogression, 4] deficit in neuroprotection. Results: Sixty-five articles were analyzed and a narrative/ theoretical review was conducted. Studies showed that insomnia, sleep loss and sleep deprivation might impair brain plasticity of those areas involved in mood regulation throughout different pathways. Insomnia and disrupted sleep may act as neurobiological stressors that by over-activating the stress and inflammatory systems may affect neural plasticity causing neuronal damage. In addition, disturbed sleep may favor a deficit in neuroprotection hence contributing to impaired neuroplasticity. Conclusions: Insomnia and disturbed sleep may play a role as markers of alteration in brain plasticity in mood disorders. Assessing and targeting insomnia in the clinical practice may potentially play a neuroprotective role, contributing to “repairing” alterations in neuroplasticity or to the functional recovery of those areas involved in mood and emotion regulation.

Adaptive and Maladaptive Neural Plasticity Due to Facial Nerve Palsy

2016 ◽  
Vol 224 (2) ◽  
pp. 102-111 ◽  
Author(s):  
Carsten M. Klingner ◽  
Stefan Brodoehl ◽  
Gerd F. Volk ◽  
Orlando Guntinas-Lichius ◽  
Otto W. Witte
Keyword(s):  
Facial Nerve ◽  
Neural Plasticity ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Motor Nerve ◽  
Predictive Coding ◽  
Theoretical Framework ◽  
Cortical Reorganization ◽  
Nerve Lesion ◽  
Peripheral Facial Palsy

Abstract. This paper reviews adaptive and maladaptive mechanisms of cortical plasticity in patients suffering from peripheral facial palsy. As the peripheral facial nerve is a pure motor nerve, a facial nerve lesion is causing an exclusive deefferentation without deafferentation. We focus on the question of how the investigation of pure deefferentation adds to our current understanding of brain plasticity which derives from studies on learning and studies on brain lesions. The importance of efference and afference as drivers for cortical plasticity is discussed in addition to the crossmodal influence of different competitive sensory inputs. We make the attempt to integrate the experimental findings of the effects of pure deefferentation within the theoretical framework of cortical responses and predictive coding. We show that the available experimental data can be explained within this theoretical framework which also clarifies the necessity for maladaptive plasticity. Finally, we propose rehabilitation approaches for directing cortical reorganization in the appropriate direction and highlight some challenging questions that are yet unexplored in the field.

Unraveling the neuroimaging predictors for motor dysfunction in long-standing multiple sclerosis

Neurology ◽  
2015 ◽  
Vol 85 (3) ◽  
pp. 248-255 ◽  
Author(s):  
Marita Daams ◽  
Martijn D. Steenwijk ◽  
Mike P. Wattjes ◽  
Jeroen J.G. Geurts ◽  
Bernard M.J. Uitdehaag ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Motor Dysfunction

Therapeutic Effects of Physical Exercise and the Mesenchymal Stem Cell Secretome by Modulating Neuroinflammatory Response in Multiple Sclerosis

2021 ◽  
Vol 16 ◽  
Author(s):  
Lina María González ◽  
Laura Natalia Ospina ◽  
Laura Elena Sperling ◽  
Orlando Chaparro ◽  
Jaison Daniel Cucarián
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Physical Exercise ◽  
Disease Progression ◽  
Neuronal Damage ◽  
Experimental Studies ◽  
Chronic Inflammatory Disease ◽  
Therapeutic Effects ◽  
Local Inflammatory Response ◽  
Neuroinflammatory Response

Multiple sclerosis (MS) is a neurodegenerative, demyelinating, and chronic inflammatory disease characterized by central nervous system (CNS) lesions that lead to high levels of disability and severe physical and cognitive disturbances. Conventional therapies are not enough to control the neuroinflammatory process in MS and are not able to inhibit ongoing damage to the CNS. Thus, the secretome of mesenchymal stem cells (MSC-S) has been postulated as a potential therapy that could mitigate symptoms and disease progression. We considered that its combination with physical exercise (EX) could induce superior effects and increase the MSC-S effectiveness in this condition. Recent studies have revealed that both EX and MSC-S share similar mechanisms of action that mitigate auto-reactive T cell infiltration, regulate the local inflammatory response, modulate the proinflammatory profile of glial cells, and reduce neuronal damage. Clinical and experimental studies have reported that these treatments in an isolated way also improve myelination, regeneration, promote the release of neurotrophic factors, and increase the recruitment of endogenous stem cells. Together, these effects reduce disease progression and improve patient functionality. Despite these results, the combination of these methods has not yet been studied in MS. In this review, we focus on molecular elements and cellular responses induced by these treatments in a separate way, showing their beneficial effects in the control of symptoms and disease progression in MS, as well as indicating their contribution in clinical fields. In addition, we propose the combined use of EX and MSC-S as a strategy to boost their reparative and immunomodulatory effects in this condition, combining their benefits on synaptogenesis, neurogenesis, remyelination, and neuroinflammatory response. The findings here reported are based on the scientific evidence and our professional experience that will bring significant progress to regenerative medicine to deal with this condition.

scholarly journals Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies

npj Vaccines ◽  
2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Changyoun Kim ◽  
Armine Hovakimyan ◽  
Karen Zagorski ◽  
Tatevik Antonyan ◽  
Irina Petrushina ◽  
...  
Keyword(s):  
Dna Vaccines ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
The Elderly ◽  
Brain Regions ◽  
Dependent Manner ◽  
Lewy Neurites ◽  
The Brain

AbstractAccumulation of misfolded proteins such as amyloid-β (Aβ), tau, and α-synuclein (α-Syn) in the brain leads to synaptic dysfunction, neuronal damage, and the onset of relevant neurodegenerative disorder/s. Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are characterized by the aberrant accumulation of α-Syn intracytoplasmic Lewy body inclusions and dystrophic Lewy neurites resulting in neurodegeneration associated with inflammation. Cell to cell propagation of α-Syn aggregates is implicated in the progression of PD/DLB, and high concentrations of anti-α-Syn antibodies could inhibit/reduce the spreading of this pathological molecule in the brain. To ensure sufficient therapeutic concentrations of anti-α-Syn antibodies in the periphery and CNS, we developed four α-Syn DNA vaccines based on the universal MultiTEP platform technology designed especially for the elderly with immunosenescence. Here, we are reporting on the efficacy and immunogenicity of these vaccines targeting three B-cell epitopes of hα-Syn aa85–99 (PV-1947D), aa109–126 (PV-1948D), aa126–140 (PV-1949D) separately or simultaneously (PV-1950D) in a mouse model of synucleinopathies mimicking PD/DLB. All vaccines induced high titers of antibodies specific to hα-Syn that significantly reduced PD/DLB-like pathology in hα-Syn D line mice. The most significant reduction of the total and protein kinase resistant hα-Syn, as well as neurodegeneration, were observed in various brain regions of mice vaccinated with PV-1949D and PV-1950D in a sex-dependent manner. Based on these preclinical data, we selected the PV-1950D vaccine for future IND enabling preclinical studies and clinical development.

scholarly journals Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia

2020 ◽  
Author(s):  
Steven F. Grieco ◽  
Xin Qiao ◽  
Xiaoting Zheng ◽  
Yongjun Liu ◽  
Lujia Chen ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Neural Plasticity ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Excitatory Input ◽  
Inhibitory Neurons ◽  
List Type ◽  
Visual Cortical

SummarySubanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine’s effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces down-regulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.Highlights○ Disinhibition of excitatory cells by ketamine occurs in a fast and sustained manner○ Ketamine evokes NRG1 downregulation and excitatory input loss to PV cells○ Ketamine induced plasticity is blocked by exogenous NRG1 or its receptor knockout○ PV inhibitory cells are the initial functional locus underlying ketamine’s effects

scholarly journals Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease

2015 ◽  
Vol 26 (24) ◽  
pp. 4478-4491 ◽  
Author(s):  
BK. Binukumar ◽  
Varsha Shukla ◽  
Niranjana D. Amin ◽  
Philip Grant ◽  
M. Bhaskar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Selective Inhibition ◽  
Motor Dysfunction ◽  
Dopamine Neurons ◽  
Dopamine Depletion ◽  
Neuroprotective Effects

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. Recent evidence indicates that cyclin-dependent kinase 5 (Cdk5) is inappropriately activated in several neurodegenerative conditions, including PD. To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity. Previously we reported that TFP5 peptide has neuroprotective effects in animal models of Alzheimer’s disease. Here we show that TFP5/TP5 selective inhibition of Cdk5/p25 hyperactivation in vivo and in vitro rescues nigrostriatal dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP/MPP+) in a mouse model of PD. TP5 peptide treatment also blocked dopamine depletion in the striatum and improved gait dysfunction after MPTP administration. The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Here we show selective inhibition of Cdk5/p25 ­hyperactivation by TFP5/TP5 peptide, which identifies the kinase as a potential therapeutic target to reduce neurodegeneration in Parkinson’s disease.

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