Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy

Bernstein, Hans‐Gert; Keilhoff, Gerburg; Laube, Gregor; Dobrowolny, Henrik; Steiner, Johann

doi:10.5498/wjp.v11.i12.1177

Cited by 5 publications

(3 citation statements)

References 105 publications

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“…PAs play a key role in brain function and cell survival [ 12 , 34 , 40 , 47 , 115 , 116 , 117 ]. Recently, it was reviewed that PAs are anti-inflammatory, antioxidant, antithrombotic, antidepressant [ 10 , 11 , 13 , 15 , 16 , 118 ], and neuroprotective [ 55 ]. Indeed, both SPM and SPD have demonstrated similar effects.…”

Section: Discussionmentioning

confidence: 99%

“…Astrocytes are connected by large diameter connexin (Cx) gap junction pores (GJs) that facilitate astrocytic communication and function [ 1 , 2 , 3 , 4 ]. Over the past decade, the interest about astrocytes [ 5 , 6 , 7 , 8 ] and polyamines (PAs) in the nervous system [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ] has increased. Astrocytes have extensive communication via Cx GJ channels that make the three-dimensional astrocytic syncytium large, electrically isopotential [ 4 , 19 ], and unique [ 10 , 11 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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The Polyamine Spermine Potentiates the Propagation of Negatively Charged Molecules through the Astrocytic Syncytium

et al. 2022

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The interest in astrocytes, the silent brain cells that accumulate polyamines (PAs), is growing. PAs exert anti-inflammatory, antioxidant, antidepressant, neuroprotective, and other beneficial effects, including increasing longevity in vivo. Unlike neurons, astrocytes are extensively coupled to others via connexin (Cx) gap junctions (GJs). Although there are striking modulatory effects of PAs on neuronal receptors and channels, PA regulation of the astrocytic GJs is not well understood. We studied GJ-propagation using molecules of different (i) electrical charge, (ii) structure, and (iii) molecular weight. Loading single astrocytes with patch pipettes containing membrane-impermeable dyes, we observed that (i) even small molecules do not easily permeate astrocytic GJs, (ii) the ratio of the charge to weight of these molecules is the key determinant of GJ permeation, (iii) the PA spermine (SPM) induced the propagation of negatively charged molecules via GJs, (iv) while no effects were observed on propagation of macromolecules with net-zero charge. The GJ uncoupler carbenoxolone (CBX) blocked such propagation. Taken together, these findings indicate that SPM is essential for astrocytic GJ communication and selectively facilitates intracellular propagation via GJs for negatively charged molecules through glial syncytium.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Polyamine Spermine Potentiates the Propagation of Negatively Charged Molecules through the Astrocytic Syncytium

et al. 2022

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“…In neurodegenerative diseases, augmented PA metabolism results in the generation of H 2 O 2 and reactive aldehydes including acrolein, which participate in the death of compromised tissue [ 77 ]. Indeed, while SMOX activity in the healthy brain was found in some neurons, SMOX upregulation and overexpression was found in both PD [ 78 ] and AD [ 51 ] and in some CNS diseases [ 79 ]. SMOX induction has been reported in diabetic retinopathy [ 56 ] as well as in brain ischemia [ 54 ]; in these pathological conditions, the upregulation of SMOX seems to be responsible for neuron damage (see Figure 3 ).…”

Section: Polyamine Catabolism: the Enzyme Smoxmentioning

confidence: 99%

The Involvement of Polyamines Catabolism in the Crosstalk between Neurons and Astrocytes in Neurodegeneration

et al. 2022

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In mammalian cells, the content of polyamines is tightly regulated. Polyamines, including spermine, spermidine and putrescine, are involved in many cellular processes. Spermine oxidase specifically oxidizes spermine, and its deregulated activity has been reported to be linked to brain pathologies involving neuron damage. Spermine is a neuromodulator of a number of ionotropic glutamate receptors and types of ion channels. In this respect, the Dach-SMOX mouse model overexpressing spermine oxidase in the neocortex neurons was revealed to be a model of chronic oxidative stress, excitotoxicity and neuronal damage. Reactive astrocytosis, chronic oxidative and excitotoxic stress, neuron loss and the susceptibility to seizure in the Dach-SMOX are discussed here. This genetic model would help researchers understand the linkage between polyamine dysregulation and neurodegeneration and unveil the roles of polyamines in the crosstalk between astrocytes and neurons in neuroprotection or neurodegeneration.

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Multiomics Analyses Reveal Microbiome–Gut–Brain Crosstalk Centered on Aberrant Gamma-Aminobutyric Acid and Tryptophan Metabolism in Drug-Naïve Patients with First-Episode Schizophrenia

Wang

Yuan

Zhu

et al. 2023

Schizophrenia Bulletin

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Background and Hypothesis Schizophrenia (SCZ) is associated with complex crosstalk between the gut microbiota and host metabolism, but the underlying mechanism remains elusive. Investigating the aberrant neurotransmitter processes reflected by alterations identified using multiomics analysis is valuable to fully explain the pathogenesis of SCZ. Study Design We conducted an integrative analysis of multiomics data, including the serum metabolome, fecal metagenome, single nucleotide polymorphism data, and neuroimaging data obtained from a cohort of 127 drug-naïve, first-episode SCZ patients and 92 healthy controls to characterize the microbiome–gut–brain axis in SCZ patients. We used pathway-based polygenic risk score (PRS) analyses to determine the biological pathways contributing to genetic risk and mediation effect analyses to determine the important neuroimaging features. Additionally, a random forest model was generated for effective SCZ diagnosis. Study Results We found that the altered metabolome and dysregulated microbiome were associated with neuroactive metabolites, including gamma-aminobutyric acid (GABA), tryptophan, and short-chain fatty acids. Further structural and functional magnetic resonance imaging analyses highlighted that gray matter volume and functional connectivity disturbances mediate the relationships between Ruminococcus_torgues and Collinsella_aerofaciens and symptom severity and the relationships between species Lactobacillus_ruminis and differential metabolites l-2,4-diaminobutyric acid and N-acetylserotonin and cognitive function. Moreover, analyses of the Polygenic Risk Score (PRS) support that alterations in GABA and tryptophan neurotransmitter pathways are associated with SCZ risk, and GABA might be a more dominant contributor. Conclusions This study provides new insights into systematic relationships among genes, metabolism, and the gut microbiota that affect brain functional connectivity, thereby affecting SCZ pathogenesis.

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Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy

Cited by 5 publications

References 105 publications

The Polyamine Spermine Potentiates the Propagation of Negatively Charged Molecules through the Astrocytic Syncytium

The Polyamine Spermine Potentiates the Propagation of Negatively Charged Molecules through the Astrocytic Syncytium

The Involvement of Polyamines Catabolism in the Crosstalk between Neurons and Astrocytes in Neurodegeneration

Multiomics Analyses Reveal Microbiome–Gut–Brain Crosstalk Centered on Aberrant Gamma-Aminobutyric Acid and Tryptophan Metabolism in Drug-Naïve Patients with First-Episode Schizophrenia

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