MicroRNA-186-5p controls GluA2 surface expression and synaptic scaling in hippocampal neurons

Silva, Mariline M; Rodrigues, Beatriz; Fernandes, Júlia; Santos, Sandra Dos; Carreto, Laura; Santos, Manuel A. S.; Pinheiro, Paulo S.; Carvalho, Ana Luı́sa

doi:10.1073/pnas.1900338116

Cited by 50 publications

(51 citation statements)

References 89 publications

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“…According to the literature, miR-375 is relevant to psychiatric conditions and psychological phenotypes ( Bhinge et al., 2016 ; Dulcis et al., 2017 ), while chronic unpredictable stress can cause miR-375 increase thus affecting expression of relevant genes ( Lotan et al., 2018 ). In turn, the role of miR-186 in synaptic scaling as a degree of stable neuronal activity affected by developmental processes was demonstrated ( Silva et al., 2019 ). Therefore, future research on the connection between rs3803107 variations and depression liability via miR-375 and miR-186 binding appears to be promising.…”

Section: Discussionmentioning

confidence: 99%

AVPR1A main effect and OXTR-by-environment interplay in individual differences in depression level

Казанцева

Davydova

Enikeeva

et al. 2020

Heliyon

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Background Multiple studies of depression indicated a significant role of gene-by-environment interactions; however, they are mainly limited to the examination of modulating effect of recent stressful life events. Other environmental factors occurring at different stages of ante- and postnatal development may affect the association between multiple genes and depression. The study aimed to analyze the main and haplotype-based effect of serotonergic system and HPA-axis gene polymorphisms on depression and to detect gene-by-environment interaction models explaining individual variance in depression in mentally healthy young adults from Russia. Methods Depression score was assessed using Beck Depression Inventory (BDI) in 623 healthy individuals (81% women; 17-25 years) of Caucasian origin (Russians, Tatars, Udmurts) from Russia. The main- and gene-based effects of 12 SNPs in SLC6A4 (5-HTTLPR, rs1042173), HTR2A (rs7322347), OXTR (rs7632287, rs2254298, rs13316193, rs53576, rs2228485, rs237911), AVPR1A (rs3803107, rs1042615), and AVPR1B (rs33911258) genes, and gene-by-environment interactions were tested with linear regression models (PLINK v.1.9) adjusted for multiple comparisons. Results We observed ethnicity-specific main effect of the AVPR1A rs3803107 (P = 0.003; P FDR = 0.047) and gene-based effect of the OXTR gene (Р = 0.005; P perm = 0.034) on BDI-measured depression, and modifying effect of paternal care on OXTR rs53576 (P = 0.004; P FDR = 0.012) and birth order on OXTR rs237911 (P = 0.006; P FDR = 0.018) association with depression level. Limitations A hypothesis driven candidate gene approach, which examined a limited number of genetic variants in a moderately large sample, was used. Conclusions Our preliminary findings indicate that familial environment may play a permissive role modulating the manifestation of OXTR -based depression variance in mentally healthy subjects.

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Section: Discussionmentioning

confidence: 99%

AVPR1A main effect and OXTR-by-environment interplay in individual differences in depression level

Казанцева

Davydova

Enikeeva

et al. 2020

Heliyon

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“…One possibility is that constant a-and c-tDCS form a downward and an upward current flow along axons of neurons arranged in vertical columns, respectively (Lund et al 2003;Douglas & Martin, 2004;Ohki et al 2005), which may preferentially affect the synthesis of neurotransmitters and thus produce directionally specific neurophysiology changes (Hannah et al 2019). For example, current flow in varied directions may differently affect the transmembrane transportation of Ca 2+ (Brosenitsch & Katz, 2001), which will initiate specific genes expression by activation of its transcription factors (Hardingham et al 1998;Ma et al 2014;Fukuchi et al 2015;Puri, 2020) or suppress some genes expression through microRNA-mediated post-transcriptional silence (Lee et al 2012;Rajgor et al 2017;Wan et al 2018), including the genes expression of GABAergic and glutamatergic markers (Ma et al 2016;Zhang et al 2018;Silva et al 2019). An alternative hypothesis is that a-and c-tDCS may respectively activate and inactivate glial astrocytes, as reported recently (Monai et al 2016), which can exert differential influence on GLU and GABA syntheses by affecting the GLN-GLU/GABA metabolic cycle (Jacob et al 2014;Walls et al 2015;Zheng et al 2016;Albrecht & Zielińska, 2017).…”

Section: Study Limitationsmentioning

confidence: 99%

Anodal and cathodal tDCS modulate neural activity and selectively affect GABA and glutamate syntheses in the visual cortex of cats

Zhao

Ding

Pan

et al. 2020

The Journal of Physiology

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Key points The present study showed that anodal and cathodal transcranial direct current stimulation (tDCS) can respectively increase and decrease the amplitude of visually evoked field potentials in the stimulated visual cortex of cats, with the effect lasting for ∼60–70 min. We directly measured tDCS‐induced changes in the concentration of inhibitory and excitatory neurotransmitters in the visual cortex using the enzyme‐linked immunosorbent assay method and showed that anodal and cathodal tDCS can selectively decrease the concentration of GABA and glutamate in the stimulated cortical area. Anodal and cathodal tDCS can selectively inhibit the synthesis of GABA and glutamate by suppressing the expression of GABA‐ and glutamate‐synthesizing enzymes, respectively. Abstract Transcranial direct current stimulation (tDCS) evokes long‐lasting neuronal excitability in the target brain region. The underlying neural mechanisms remain poorly understood. The present study examined tDCS‐induced alterations in neuronal activities, as well as the concentration and synthesis of GABA and glutamate (GLU), in area 21a (A21a) of cat visual cortex. Our analysis showed that anodal and cathodal tDCS respectively enhanced and suppressed neuronal activities in A21a, as indicated by a significantly increased and decreased amplitude of visually evoked field potentials (VEPs). The tDCS‐induced effect lasted for ∼60–70 min. By contrast, sham tDCS had no significant impact on the VEPs in A21a. On the other hand, the concentration of GABA, but not that of GLU, in A21a significantly decreased after anodal tDCS relative to sham tDCS, whereas the concentration of GLU, but not that of GABA, in A21a significantly decreased after cathodal tDCS relative to sham tDCS. Furthermore, the expression of GABA‐synthesizing enzymes GAD65 and GAD67 in A21a significantly decreased in terms of both mRNA and protein concentrations after anodal tDCS relative to sham tDCS, whereas that of GLU‐synthesizing enzyme glutaminase (GLS) did not change significantly after anodal tDCS. By contrast, both mRNA and protein concentrations of GLS in A21a significantly decreased after cathodal tDCS relative to sham tDCS, whereas those of GAD65/GAD67 showed no significant change after cathodal tDCS. Taken together, these results indicate that anodal and cathodal tDCS may selectively reduce GABA and GLU syntheses and thus respectively enhance and suppress neuronal excitability in the stimulated brain area.

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“…Interestingly, a 24 h activity-deprivation paradigm in cultured hippocampal neurons using non-competitive antagonists of AMPARs and NMDARs (GYKI-52466 and MK-801, respectively) does not affect miR-92a or miR-124 levels but rather downregulates miR-186-5p, a miRNA which also targets GluA2, thereby leading to the synaptic insertion of GluA2-containing AMPARs which are not permeable to calcium (Silva et al, 2019). Finally, a 24–48 h treatment with TTX alone induces the insertion of GluA2-containing AMPARs (Sutton et al, 2006; Gainey et al, 2009), but a specific regulation of this process by miRs has not been reported yet.…”

Section: Mirna-dependent Control Of Post-synaptic Function During Hommentioning

confidence: 99%

miRNA-Dependent Control of Homeostatic Plasticity in Neurons

Dubes

Favereaux

Thoumine

et al. 2019

Front. Cell. Neurosci.

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Homeostatic plasticity is a form of plasticity in which neurons compensate for changes in neuronal activity through the control of key physiological parameters such as the number and the strength of their synaptic inputs and intrinsic excitability. Recent studies revealed that miRNAs, which are small non-coding RNAs repressing mRNA translation, participate in this process by controlling the translation of multiple effectors such as glutamate transporters, receptors, signaling molecules and voltage-gated ion channels. In this review, we present and discuss the role of miRNAs in both cell-wide and compartmentalized forms of homeostatic plasticity as well as their implication in pathological processes associated with homeostatic failure.

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MicroRNA-186-5p controls GluA2 surface expression and synaptic scaling in hippocampal neurons

Cited by 50 publications

References 89 publications

AVPR1A main effect and OXTR-by-environment interplay in individual differences in depression level

AVPR1A main effect and OXTR-by-environment interplay in individual differences in depression level

Anodal and cathodal tDCS modulate neural activity and selectively affect GABA and glutamate syntheses in the visual cortex of cats

miRNA-Dependent Control of Homeostatic Plasticity in Neurons

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