Intracranial Self-Stimulation Modulates Levels of SIRT1 Protein and Neural Plasticity-Related microRNAs

Puig-Parnau, Irene; García-Brito, Soleil; Faghihi, Nastaran; Gubern, Carme; Aldavert-Vera, Laura; Segura-Torres, Pilar; Huguet, Gemma; Kádár, Elisabet

doi:10.1007/s12035-020-01901-w

Cited by 17 publications

(13 citation statements)

References 65 publications

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“…miR‐495‐3p targets are enriched for addiction and pro‐survival genes, including BDNF, CAMK2, and ARC 41 . Furthermore, miR‐495‐3p expression is upregulated following deep brain stimulation 42 . Collectively, it is documented that these three miRNAs have a rather negative impact on neuronal processes affected in PD, however, further work is required to better delineate their roles, and if/how their higher expression in males affects vulnerability to PD.…”

Section: Discussionmentioning

confidence: 99%

Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients

Ravanidis

Bougea

Papagiannakis

et al. 2020

Ann Clin Transl Neurol

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Objective There is a pressing need to identify and validate, minimally invasive, molecular biomarkers that will complement current practices and increase the diagnostic accuracy in Parkinson’s disease (PD). Brain‐enriched miRNAs regulate all aspects of neuron development and function; importantly, they are secreted by neurons in amounts that can be readily detected in the plasma. Τhe aim of the present study was to validate a set of previously identified brain‐enriched miRNAs with diagnostic potential for idiopathic PD and recognize the molecular pathways affected by these deregulated miRNAs. Methods RT‐qPCR was performed in the plasma of 92 healthy controls and 108 idiopathic PD subjects. Statistical and in silico analyses were used to validate deregulated miRNAs and pathways in PD, respectively. Results miR‐22‐3p, miR‐124‐3p, miR‐136‐3p, miR‐154‐5p, and miR‐323a‐3p levels were found to be differentially expressed between healthy controls and PD patients. miR‐330‐5p, miR‐433‐3p, and miR‐495‐3p levels were overall higher in male subjects. Most of these miRNAs are clustered at Chr14q32 displaying CREB1, CEBPB, and MAZ transcription factor binding sites. Gene Ontology annotation analysis of deregulated miRNA targets revealed that “Protein modification,” “Transcription factor activity,” and “Cell death” terms were over‐represented. Kyoto Encyclopedia of Genes and Genome analysis revealed that “Long‐term depression,” “TGF‐beta signaling,” and “FoxO signaling” pathways were significantly affected. Interpretation We validated a panel of brain‐enriched miRNAs that can be used along with other measures for the detection of PD, revealed molecular pathways targeted by these deregulated miRNAs, and identified upstream transcription factors that may be directly implicated in PD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients

Ravanidis

Bougea

Papagiannakis

et al. 2020

Ann Clin Transl Neurol

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show abstract

“…miR-495-3p targets are enriched for addiction and pro-survival genes, including BDNF, CAMK2 and ARC [41]. Furthermore, miR-495-3p expression is upregulated following deep brain stimulation [42].…”

Section: Discussionmentioning

confidence: 99%

Validation of Differentially Expressed Brain-Enriched microRNAs in the Plasma of Parkinson’s Disease Patients

Ravanidis¹,

Bougea

Papagiannakis

et al. 2020

Preprint

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Background There is a pressing need to identify and validate, minimally invasive, molecular biomarkers that will complement current practices and increase the diagnostic accuracy in Parkinson’s disease (PD). Brain-enriched miRNAs regulate all aspects of neuron development and function; importantly, they are secreted by neurons in amounts that can be readily detected in the plasma. Τhe aim of the present study was to validate a set of previously identified brain-enriched miRNAs with a diagnostic potential for idiopathic PD and recognize the molecular pathways affected by these deregulated miRNAs.Methods RT-qPCR was performed in the plasma of 92 healthy controls and 108 idiopathic PD subjects. Statistical and in silico analyses were used to validate deregulated miRNAs and pathways in PD, respectively.Results miR-22-3p, miR-124-3p, miR-136-3p, miR-154-5p and miR-323a-3p levels were found to be differentially expressed between healthy controls and PD patients. miR-330-5p, miR-433-3p and miR-495-3p levels were overall higher in male subjects. Most of these miRNAs are clustered at Chr14q32 displaying CREB1, CEBPB, and MAZ transcription factor binding sites. Gene Ontology (GO) annotation analysis of deregulated miRNA targets revealed that ‘Protein modification’, ‘Transcription factor activity’ and ‘Cell death’ terms were over-represented. Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that ‘Long-term depression’, ‘TGF-beta signaling’, and ‘FoxO signaling’ pathways were significantly affected.Conclusions We validated a panel of brain-enriched miRNAs that can be used along with other measures for the detection of PD, revealed molecular pathways targeted by these deregulated miRNAs, and identified upstream transcription factors that may be directly implicated in their regulation and thereafter PD pathogenesis.

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“…(both theta and alpha bands, p > 0.4). The i8Hz treatment increased coherence in the alpha band (8)(9)(10)(11)(12) in one patient (Wilkinson signed-rank, p = 0.002), while no significant changes were observed in the other six (Wilkinson signed-rank, both p > 0.2).…”

mentioning

confidence: 90%

“…In DBS, the therapeutic effect is thought to be related to acutely enhancing or inhibiting activity in specific brain regions and until recently, less emphasis was placed on the potential contributing role of neural plasticity induced by electrical stimulation. Despite the important role of neural plasticity as part of the therapeutic effects in DBS [12][13][14], there is still much to learn about the most efficient plasticity inducing stimulation parameters using this approach [15].…”

Section: Introductionmentioning

confidence: 99%

Enhancing neuronal plasticity through intracranial theta burst stimulation in the human sensorimotor cortex

Herrero

Smith

Mishra

et al. 2021

Preprint

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The progress of therapeutic neuromodulation greatly depends on improving stimulation parameters to most efficiently induce neuroplasticity effects. Intermittent Theta Burst stimulation (iTBS), a form of electrical stimulation that mimics the natural brain activity patterns, has shown efficacy in inducing such effects in animal studies and rhythmic Transcranial Magnetic Stimulation (rTMS) studies in humans. However, little is known about the potential neuroplasticity effects of iTBS applied through intracranial electrodes in humans which could have implications for deep brain stimulation therapies. This study characterizes the physiological effects of cortical iTBS in the human cortex and compare them with single pulse alpha stimulation, another frequently used paradigm in rTMS research. We applied these stimulation paradigms to well-defined regions in the sensorimotor cortex which elicited contralateral hand or arm muscle contractions during electrical stimulation mapping in epilepsy patients implanted with intracranial electrodes. Treatment effects were evaluated using effective connectivity and beta oscillations coherence measures in areas connected to the treatment site as defined with cortico-cortical evoked potentials. Our results show that iTBS increases beta band synchronization within the sensorimotor network indicating a potential neuroplasticity effect. The effect is specific to the sensorimotor system, the beta frequency band and the stimulation pattern (no effect was found with single-pulse alpha stimulation). The effects outlasted the stimulation by three minutes. By characterizing the neurophysiological effects of iTBS within well-defined cortical networks, we hope to provide an electrophysiological framework that allows clinicians and researchers to optimize brain stimulation protocols which may have translational value.

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Intracranial Self-Stimulation Modulates Levels of SIRT1 Protein and Neural Plasticity-Related microRNAs

Cited by 17 publications

References 65 publications

Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients

Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients

Validation of Differentially Expressed Brain-Enriched microRNAs in the Plasma of Parkinson’s Disease Patients

Enhancing neuronal plasticity through intracranial theta burst stimulation in the human sensorimotor cortex

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