Inhibition of miR-15a Promotes BDNF Expression and Rescues Dendritic Maturation Deficits in MeCP2-Deficient Neurons

Gao, Yu; Su, Juan; Guo, Weixiang; Polich, Eric D.; Magyar, Daniel P.; Xing, Yina; Li, Hongda; Smrt, Richard D.; Chang, Qiang; Zhao, Xinyu

doi:10.1002/stem.1950

Cited by 54 publications

(48 citation statements)

References 69 publications

(127 reference statements)

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“…Downregulation of miR132 is linked with increased neuronal tolerance to ischemia [19], while miR134 is involved in memory formation and ischemic injury [20,24]. Moreover, neuronal maturation might be epigenetically controlled by miR15a [21], while miR146 acts as an epigenetic regulator of inflammation [22]. According to Hou et al [23], homeostatic synaptic plasticity is a compensatory mechanism for long-term suppression of the neuronal activity, maintaining the functionality of neuronal networks.…”

Section: Discussionmentioning

confidence: 99%

Maternal High-Fat Diet Modifies the Immature Hippocampus Vulnerability to Perinatal Asphyxia in Rats

Isac¹,

Panaitescu²,

Ieșanu

et al. 2018

Neonatology

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Background: High-fat diet (HFD) is a detrimental habit with harmful systemic consequences, including low-grade, long-lasting inflammation. During pregnancy, HFD can induce developmental changes. Moreover, HFD-related maternal obesity might enhance the risk of peripartum complications including hypoxic-ischemic encephalopathy secondary to perinatal asphyxia (PA). Objectives: Following our previous results showing that PA increases neuroinflammation and neuronal injury in the immature hippocampus and modifies hippocampal epigenetic programming, we further aimed to establish the impact of maternal HFD on offspring hippocampus response to PA. Methods: We assessed hippocampal tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1b) and S-100B protein (S-100B), 24–48 h after PA exposure in postnatal day 6 Wistar rats, whose mothers received either the standard diet or HFD. The expression of small non-coding microRNA species miR124, miR132, miR134, miR146, and miR15a, as epigenetic markers for the maternal dietary influence on immature hippocampus response after PA, was determined 24 h after asphyxia exposure. Metabolic activity was measured using resazurin test in hippocampal cell suspension obtained 24 h after PA. Results: Our results indicate that maternal HFD additionally increases hippocampal TNFα, IL-1b, and S-100B after PA. Also, PA associated with maternal HFD induces miR124 upregulation and miR132 downregulation relative to PA only. Metabolic activity was increased in hippocampal cells from pups whose mothers received HFD. Conclusion: HFD increases the PA-induced neuroinflammation and neuronal injury, and epigenetically influences homeostatic synaptic plasticity and neuronal tolerance to asphyxia, processes associated with a higher hippocampal cellular metabolism.

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Section: Discussionmentioning

confidence: 99%

Maternal High-Fat Diet Modifies the Immature Hippocampus Vulnerability to Perinatal Asphyxia in Rats

Isac¹,

Panaitescu²,

Ieșanu

et al. 2018

Neonatology

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“…Two miRNAs, miR‐15a and miR‐146b, are also reported to be involved in an interaction with brain‐derived neurotrophic factor (BDNF) [Lohoff et al, ; Gao et al, ]. BDNF is potent in neuronal maturation and is well‐known for its role in the pathological process underlying BPD and other related neuropsychiatric disorders [Post, ].…”

Section: Discussionmentioning

confidence: 99%

Preliminary examination of microRNA expression profiling in bipolar disorder I patients during antipsychotic treatment

Lim

Zainal

Kanagasundram

et al. 2016

American J of Med Genetics Pt B

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Although major progress has been achieved in research and development of antipsychotic medications for bipolar disorder (BPD), knowledge of the molecular mechanisms underlying this disorder and the action of atypical antipsychotics remains incomplete. The levels of microRNAs (miRNAs)-small non-coding RNA molecules that regulate gene expression, including genes involved in neuronal function and plasticity-are frequently altered in psychiatric disorders. This study aimed to examine changes in miRNA expression in bipolar mania patients after treatment with asenapine and risperidone. Using a miRNA microarray, we analyzed miRNA expression in the blood of 10 bipolar mania patients following 12 weeks of treatment with asenapine or risperidone. Selected miRNAs were validated by using real-time PCR. A total of 16 miRNAs were differentially expressed after treatment in the asenapine group, 14 of which were significantly upregulated and the other two significantly downregulated. However, all three differentially expressed miRNAs in the risperidone group were downregulated. MiRNA target gene prediction and gene ontology analysis revealed significant enrichment for pathways associated with immune system response and regulation of programmed cell death and transcription. Our results suggest that candidate miRNAs may be involved in the mechanism of action of both antipsychotics in bipolar mania. © 2016 Wiley Periodicals, Inc.

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“…Upregulation or downregulation of MECP2 dramatically alters the dendritic and axonal architecture of neurons and significantly disrupts the connectivity of neuronal networks (Fukuda et al, 2005; Jugloff et al, 2005; Ballas et al, 2009; Belichenko et al, 2009; Chapleau et al, 2009; Kishi and Macklis, 2010; Cohen et al, 2011; Marshak et al, 2012; Nguyen et al, 2012; Stuss et al, 2012; Jiang et al, 2013a; Baj et al, 2014). Overexpression of BDNF appears to restore the dendritic defects in Mecp2 -null condition suggesting a molecular mechanism regulated by MECP2 to maintain the structural stability of neurons (Zhou et al, 2006; Larimore et al, 2009; Gao et al, 2015). Synaptic plasticity is also regulated by the expression or the phosphorylation of MECP2 (Collins et al, 2004; Dani et al, 2005; Asaka et al, 2006; Moretti et al, 2006; Chao et al, 2007; Zhang et al, 2008; Li et al, 2011; Noutel et al, 2011; Blackman et al, 2012; Na et al, 2012, 2013; Qiu et al, 2012; Zhong et al, 2012; Della Sala and Pizzorusso, 2014; Deng et al, 2014; De Filippis et al, 2015).…”

Section: Specific Syndromic Disorder Related Genesmentioning

confidence: 96%

A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons

Lin

Frei

Kilander

et al. 2016

Front. Cell. Neurosci.

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Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals’ ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interaction, communication, and behavior. Alterations in neurite arborization and dendritic spine morphology, including size, shape, and number, are hallmarks of almost all neurological conditions, including ASD. As experimental evidence emerges in recent years, it becomes clear that although there is broad heterogeneity of identified autism risk genes, many of them converge into similar cellular pathways, including those regulating neurite outgrowth, synapse formation and spine stability, and synaptic plasticity. These mechanisms together regulate the structural stability of neurons and are vulnerable targets in ASD. In this review, we discuss the current understanding of those autism risk genes that affect the structural connectivity of neurons. We sub-categorize them into (1) cytoskeletal regulators, e.g., motors and small RhoGTPase regulators; (2) adhesion molecules, e.g., cadherins, NCAM, and neurexin superfamily; (3) cell surface receptors, e.g., glutamatergic receptors and receptor tyrosine kinases; (4) signaling molecules, e.g., protein kinases and phosphatases; and (5) synaptic proteins, e.g., vesicle and scaffolding proteins. Although the roles of some of these genes in maintaining neuronal structural stability are well studied, how mutations contribute to the autism phenotype is still largely unknown. Investigating whether and how the neuronal structure and function are affected when these genes are mutated will provide insights toward developing effective interventions aimed at improving the lives of people with autism and their families.

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Inhibition of miR-15a Promotes BDNF Expression and Rescues Dendritic Maturation Deficits in MeCP2-Deficient Neurons

Cited by 54 publications

References 69 publications

Maternal High-Fat Diet Modifies the Immature Hippocampus Vulnerability to Perinatal Asphyxia in Rats

Maternal High-Fat Diet Modifies the Immature Hippocampus Vulnerability to Perinatal Asphyxia in Rats

Preliminary examination of microRNA expression profiling in bipolar disorder I patients during antipsychotic treatment

A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons

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