An Integrative Approach to Neuroinflammation in Psychiatric disorders and Neuropathic Pain

Lurie, Diana I.

doi:10.1177/1179069518793639

Cited by 83 publications

(61 citation statements)

References 105 publications

(158 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our approach identified a trophic role for neurokine signalling in cortical cholinergic systems, particularly for IL-6, distinguishing these cortical neurons from the NGF-dependent basal forebrain population. The consistent identification of inflammatory processes across all aspects of our integrative study protocol lends further support to the neuroinflammatory aspect of SCZ/BD, for example via IL6-mediated temporary overstimulation (Lurie, 2018). Basal neurokine levels in the brain are comparatively low, and current methods of measurement do not allow an analysis of short-term fluctuations in living human subjects.…”

Section: The Cholinergic/neurokine Interfacementioning

confidence: 76%

Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder

Lobentanzer

Hanin

Klein

et al. 2019

Preprint

View full text Add to dashboard Cite

135 words): RNA-sequencing analyses are often limited to identifying lowest p-value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA-sequencing of human male-and female-originated cell lines, and connectomics of transcription factor-and microRNA-interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. While these pathologies show massive transcriptional parallels, their clinically well-known sexual dimorphisms remain unexplained. Our method explicates the differences between afflicted men and women, and identifies diseaseaffected pathways of cholinergic transmission and gp130-family neurokine controllers of immune function, interlinked by microRNAs. This approach may open new perspectives for seeking biomarkers and therapeutic targets, also in other transmitter systems and diseases.Manuscript (Erta et al., 2012): the gp130 co-receptor (also known as IL6ST, IL-6 signal transducer), and the LIF-receptor. Gp130-family neurokines unite properties of neurotrophic (e.g. on dopaminergic neurons) and immunogenic nature, both prominent facets in the molecular etiology of SCZ and BD (Harrison, 2015) and in cholinergic signaling (Stanke et al., 2006). Neurokines can activate JAK1/2, TYK2 and STAT1/3/5A/5B (Rawlings, 2004), affecting neurotransmission as well as immunity. However, to the best of our knowledge, their roles in SCZ/BD were not yet studied.SCZ/BD hallmarks also involve circadian perturbations. The cholinergic-catecholaminergic imbalance in BD (Van Enkhuizen et al., 2015) follows variable transcriptionally-regulated rhythms (e.g. CLOCK, ARNTL, RORA), and affected individuals exhibit decreased REM latency (the duration from onset of sleep to the first rapid eye movement phase) and increased vulnerability for disease that can be modulated by muscarinic agonists/antagonists (Ising et al., 2005). Correspondingly, the muscarinic M1/M3 receptor genes are essential for REM sleep (Niwa et al., 2018), and sleep deprivation exerts short-term antidepressant effects (Wu and Bunney, 1990), reduced cortical ACh levels (Boonstra et al., 2007), and vast transcriptional changes in basal forebrain cholinergic neurons (Nikonova et al., 2017).The quantitative measurement of disease-relevance of individual perturbed genes is a common methodological problem in transcriptomic analyses. To reduce complexity, transcripts are often filtered by their p-values, leading to bias towards few highly expressed and differentially regulated genes. This does not agree with a polygenic model where each component contributes a small effect. To alleviate this bias while still attempting the necessary complexity reduction, we developed an integrative approach of multiple perspectives. Jerusalem and Andreas Meisel, Berlin and to Dr. Ester Bennett, Jerusalem ...

show abstract

Section: The Cholinergic/neurokine Interfacementioning

confidence: 76%

Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder

Lobentanzer

Hanin

Klein

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The Cholinergic/Neurokine Interface Our approach identified a trophic role for neurokine signaling in cortical cholinergic systems, particularly for IL-6, distinguishing these cortical neurons from the NGF-dependent basal forebrain population. The consistent identification of inflammatory processes across all aspects of our integrative study protocol lends further support to the neuroinflammatory aspect of SCZ/BD; for example, via IL-6-mediated temporary overstimulation (Lurie, 2018). Basal neurokine levels in the brain are comparatively low, and current methods of measurement do not allow analysis of short-term fluctuations in living human subjects.…”

Section: Limitationsmentioning

confidence: 78%

Integrative Transcriptomics Reveals Sexually Dimorphic Control of the Cholinergic/Neurokine Interface in Schizophrenia and Bipolar Disorder

et al. 2019

View full text Add to dashboard Cite

Graphical Abstract Highlights d Single-cell transcriptomes reveal a unique profile of cortical cholinergic neurons d Female-and male-derived cells show distinct neurokineinduced miRNA responses d Differentially enriched microRNA families constitute a selforganizing network d Integrative analysis identifies mir-10/mir-199 regulators of cholinergic function SUMMARYRNA sequencing analyses are often limited to identifying lowest p value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large-scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA sequencing of human male-and female-originating cell lines, and connectomics of transcription factor and microRNA interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. Although these pathologies show massive transcriptional parallels, their clinically well-known sexual dimorphisms remain unexplained. Our method reveals the differences between afflicted men and women and identifies disease-affected pathways of cholinergic transmission and gp130family neurokine controllers of immune function interlinked by microRNAs. This approach may open additional perspectives for seeking biomarkers and therapeutic targets in other transmitter systems and diseases.

show abstract

“…In response to glutamate, TNFα enhances neuro-excitability and rapidly up-regulates the membrane expression and conductance of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) receptors in neurons (51). TNF-α significantly upregulates the kidney type glutaminase (KGA) in cytosol and extracellular fluid of human neurons, exposing glutaminase as a potential component of neurotoxicity during inflammation (28). Along with this, the levels of Granulocyte-colony stimulating factor (G-CSF), glial fibrillary acidic protein (GFAP), microglial cells and Keratinocyte cells (KC) increases in the brain in response to AKI (52) due to the recruitment of neutrophils at the site of neuronal damage.…”

Section: Role Of Cytokines In Pain Regulation During Akimentioning

confidence: 99%

Neuroimmune Mechanisms in Signaling of Pain During Acute Kidney Injury (AKI)

et al. 2020

View full text Add to dashboard Cite

Acute kidney injury (AKI) is a significant global health concern. The primary causes of AKI include ischemia, sepsis and nephrotoxicity. The unraveled interface between nervous system and immune response with specific focus on pain pathways is generating a huge interest in reference to AKI. The nervous system though static executes functions by nerve fibers throughout the body. Neuronal peptides released by nerves effect the immune response to mediate the hemodynamic system critical to the functioning of kidney. Pain is the outcome of cellular cross talk between nervous and immune systems. The widespread release of neuropeptides, neurotransmitters and immune cells contribute to bidirectional neuroimmune cross talks for pain manifestation. Recently, we have reported pain pathway genes that may pave the way to better understand such processes during AKI. An auxiliary understanding of the functions and communications in these systems will lead to novel approaches in pain management and treatment through the pathological state, specifically during acute kidney injury.

show abstract

An Integrative Approach to Neuroinflammation in Psychiatric disorders and Neuropathic Pain

Cited by 83 publications

References 105 publications

Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder

Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder

Integrative Transcriptomics Reveals Sexually Dimorphic Control of the Cholinergic/Neurokine Interface in Schizophrenia and Bipolar Disorder

Neuroimmune Mechanisms in Signaling of Pain During Acute Kidney Injury (AKI)

Contact Info

Product

Resources

About