Neuroplasticity in Bipolar Disorder: Insights from Neuroimaging

Rocha, Marlos Vasconcelos; Nery, Fabiana; Almeida, Amanda Galvão-de; Quarantini, Lucas de Castro; Miranda‐Scippa, Ângela

doi:10.5772/67288

“…1). As alterations of neuroplasticity have been described in different neuropsychiatric disorders (Hasan and others 2011; Hsu and others 2015; Liu and others 2017; Rocha and others 2017), also characterized by cognitive impairments, tDCS appears to be a promising alternative treatment option for restoring the disequilibrium between excitatory and inhibitory neurotransmitters systems. To date, several investigations showed beneficial effects of tDCS on different cognitive domains, such as working memory and learning abilities, executive functions and attention in neuropsychiatric patients (Bersani and others 2017; Boggio and others 2012; Hoy and others 2014; Meinzer and others 2015; Pavlova and others 2018).…”

Section: Introductionmentioning

confidence: 99%

Transcranial Direct Current Stimulation and Cognition in Neuropsychiatric Disorders: Systematic Review of the Evidence and Future Directions

Ciullo

¹

,

Spalletta

²

,

Caltagirone

³

et al. 2020

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Transcranial direct current stimulation (tDCS) has been implemented in neuropsychiatric disorders characterized by cognitive impairment. However, methodological heterogeneity challenges conclusive remarks. Through a critical analysis of previous conflicting findings and in the light of current neurobiological models of pathophysiology, we qualitatively assessed the effects of tDCS in neuropsychiatric disorders that share neurobiological underpinnings, as to evaluate whether stimulation can improve cognitive deficits in patients’ cohorts. We performed a systematic review of tDCS studies targeting cognitive functions in mental disorders and pathological cognitive aging. Data from 41 studies, comprising patients with diagnosis of mood disorders, schizophrenia-spectrum disorders, Alzheimer’s disease (AD), and mild cognitive impairment (MCI), were included. Results indicate that tDCS has the capacity to enhance processing speed, working memory, and executive functions in patients with mood and schizophrenia-spectrum disorders. The evidence of a positive effect on general cognitive functioning and memory is either inconclusive in AD, or weak in MCI. Future directions are discussed for developing standardized stimulation protocols and for translating the technique therapeutic potential into effective clinical practice.

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“…SERPINB2 is involved in cell proliferation, differentiation and growth and regulates synaptic plasticity in hippocampal neurons [104]. Reduced synaptic plasticity is observed in BD [105,106] and antidepressants have been shown to enhance neuroplasticity and resilience [77][78][79]. Wnt proteins regulate several processes such as brain development, cell growth, differentiation, migration and fate determination among others, implicated in BD pathophysiology.…”

Section: Co-regulated Genesmentioning

confidence: 99%

Transcriptional analysis of sodium valproate in a serotonergic cell line reveals gene regulation through both HDAC inhibition-dependent and independent mechanisms

Sinha

¹

,

Cree

²

,

Miller

³

et al. 2021

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Sodium valproate (VPA) is a histone deacetylase (HDAC) inhibitor, widely prescribed in the treatment of bipolar disorder, and yet the precise modes of therapeutic action for this drug are not fully understood.After exposure of the rat serotonergic cell line RN46A to VPA, RNA-sequencing (RNA-Seq) analysis showed widespread changes in gene expression. Analysis by multiple pipelines revealed as many as 230 genes were significantly upregulated and 72 genes were significantly downregulated. A subset of 23 differentially expressed genes was selected for validation using the nCounter® platform, and of these we obtained robust validation for ADAM23, LSP1, MAOB, MMP13, PAK3, SERPINB2, SNAP91, WNT6, and ZCCHC12. We investigated the effect of lithium on this subset and found four genes, CDKN1C, LSP1, SERPINB2 and WNT6 co-regulated by lithium and VPA. We also explored the effects of other HDAC inhibitors and the VPA analogue valpromide on the subset of 23 selected genes.Expression of eight of these genes, CDKN1C, MAOB, MMP13, NGFR, SHANK3, VGF, WNT6 and ZCCHC12, was modified by HDAC inhibition, whereas others did not appear to respond to several HDAC inhibitors tested. These results suggest VPA may regulate genes through both HDAC-dependent and independent mechanisms. Understanding the broader gene regulatory effects of VPA in this serotonergic cell model should provide insights into how this drug works and whether other HDACi compounds may have similar gene regulatory effects, as well as highlighting molecular processes that may underlie regulation of mood.Dysregulation of the serotonergic system has been implicated in the pathophysiology of mood disorders [18]. The serotonergic neurons originate from the median and the dorsal raphe nucleus in the brain stem and project to different brain regions, where they secrete serotonin which regulates mood [37]. In this study, we examined the gene expression effects of VPA using the neural cell line RN46A, derived from the rat medullary raphe region [38], which has been used previously to study gene expression in response to antidepressants and mood stabilisers [39][40][41][42][43][44]. Differentiated RN46A cells express all 5-HT receptors 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C and the serotonin transporter SERT [38,45].Understanding the transcriptional effects of VPA in a relevant cellular context may provide clues to its mechanisms of action. Previous studies in our laboratory using the RN46A cell line revealed differential gene expression in response to VPA exposure [41,44]. In this paper, we sought to extend these findings using RNA-Seq as a discovery tool for differentially expressed genes (DEG), followed by validation of a subset of these genes using an orthogonal gene expression analysis method. Furthermore, we examined the action of other mood stabilizing drugs and other HDACi compounds on expression of this subset of genes. Methods Cell culture and RNA extractionThe RN46A cells were maintained at 33 o C in Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12 (DMEM/F12; ThermoF...

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Transcriptional analysis of sodium valproate in a serotonergic cell line reveals gene regulation through both HDAC inhibition-dependent and independent mechanisms

Sinha

¹

,

Cree

²

,

Miller

³

et al. 2019

Preprint

View full text Add to dashboard Cite

Sodium valproate (VPA) is a histone deacetylase (HDAC) inhibitor, widely prescribed in the treatment of bipolar disorder, and yet the precise modes of therapeutic action for this drug are not fully understood.After exposure of the rat serotonergic cell line RN46A to VPA, RNA-sequencing (RNA-Seq) analysis showed widespread changes in gene expression. Analysis by multiple pipelines revealed as many as 230 genes were significantly upregulated and 72 genes were significantly downregulated. A subset of 23 differentially expressed genes was selected for validation using the nCounter® platform, and of these we obtained robust validation for ADAM23, LSP1, MAOB, MMP13, PAK3, SERPINB2, SNAP91, WNT6, and ZCCHC12. We investigated the effect of lithium on this subset and found four genes, CDKN1C, LSP1, SERPINB2 and WNT6 co-regulated by lithium and VPA. We also explored the effects of other HDAC inhibitors and the VPA analogue valpromide on the subset of 23 selected genes. Expression of eight of these genes, CDKN1C, MAOB, MMP13, NGFR, SHANK3, VGF, WNT6 and ZCCHC12, was modified by HDAC inhibition, whereas others did not appear to respond to several HDAC inhibitors tested. These results suggest VPA may regulate genes through both HDAC-dependent and independent mechanisms. Understanding the broader gene regulatory effects of VPA in this serotonergic cell model should provide insights into how this drug works and whether other HDACi compounds may have similar gene regulatory effects, as well as highlighting molecular processes that may underlie regulation of mood.

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Neuroplasticity in Bipolar Disorder: Insights from Neuroimaging

Cited by 3 publications

References 103 publications

Transcranial Direct Current Stimulation and Cognition in Neuropsychiatric Disorders: Systematic Review of the Evidence and Future Directions

Transcranial Direct Current Stimulation and Cognition in Neuropsychiatric Disorders: Systematic Review of the Evidence and Future Directions

Transcriptional analysis of sodium valproate in a serotonergic cell line reveals gene regulation through both HDAC inhibition-dependent and independent mechanisms

Transcriptional analysis of sodium valproate in a serotonergic cell line reveals gene regulation through both HDAC inhibition-dependent and independent mechanisms

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