The non-coding RNA BC1 regulates experience-dependent structural plasticity and learning

Briz, Victor; Restivo, Leonardo; Pasciuto, Emanuela; Juczewski, Konrad; Mercaldo, Valentina; Lo, Adrian C.; Baatsen, Pieter; Gounko, Natalia V.; Borreca, Antonella; Girardi, Tiziana; Lucà, Rossella; Nys, Julie; Poorthuis, Rogier B.; Mansvelder, Huibert D.; Fisone, Gilberto; Ammassari–Teule, Martine; Arckens, Lutgarde; Krieger, Patrik; Meredith, Rhiannon M.; Bagni, Claudia

doi:10.1038/s41467-017-00311-2

Cited by 46 publications

(34 citation statements)

References 82 publications

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“…Phenotypic alterations in BC1 KO animals ( Zhong et al, 2009 ; Briz et al, 2017 ; Iacoangeli et al, 2017 ) are caused by global lack of regulatory BC1 RNA. It was formally possible that phenotypic alterations in CGG animals were also caused by a reduction of brain BC1 RNA expression levels, in addition to cellular BC1 RNA mislocalization as described above.…”

Section: Resultsmentioning

confidence: 99%

BC RNA Mislocalization in the Fragile X Premutation

Muslimov

Eom

Iacoangeli

et al. 2018

eNeuro

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Fragile X premutation disorder is caused by CGG triplet repeat expansions in the 5′ untranslated region of FMR1 mRNA. The question of how expanded CGG repeats cause disease is a subject of continuing debate. Our work indicates that CGG-repeat structures compete with regulatory BC1 RNA for access to RNA transport factor hnRNP A2. As a result, BC1 RNA is mislocalized in vivo, as its synapto-dendritic presence is severely diminished in brains of CGG-repeat knock-in animals (a premutation mouse model). Lack of BC1 RNA is known to cause seizure activity and cognitive dysfunction. Our working hypothesis thus predicted that absence, or significantly reduced presence, of BC1 RNA in synapto-dendritic domains of premutation animal neurons would engender cognate phenotypic alterations. Testing this prediction, we established epileptogenic susceptibility and cognitive impairments as major phenotypic abnormalities of CGG premutation mice. In CA3 hippocampal neurons of such animals, synaptic release of glutamate elicits neuronal hyperexcitability in the form of group I metabotropic glutamate receptor–dependent prolonged epileptiform discharges. CGG-repeat knock-in animals are susceptible to sound-induced seizures and are cognitively impaired as revealed in the Attentional Set Shift Task. These phenotypic disturbances occur in young-adult premutation animals, indicating that a neurodevelopmental deficit is an early-initial manifestation of the disorder. The data are consistent with the notion that RNA mislocalization can contribute to pathogenesis.

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Section: Resultsmentioning

confidence: 99%

BC RNA Mislocalization in the Fragile X Premutation

Muslimov

Eom

Iacoangeli

et al. 2018

eNeuro

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“…Novel object recognition experiments were conducted in a 30 cm × 30 cm × 20 cm field arena. For the object recognition test, we adapted a protocol previously described in several studies ( Bevins and Besheer, 2006 ; Leger et al, 2013 ; Briz et al, 2017 ; Volmar et al, 2017 ). The test comprised training and testing phases.…”

Section: Methodsmentioning

confidence: 99%

Inhibiting RIP1 Improves Chronic Stress-Induced Cognitive Impairments in D-Galactose-Induced Aging Mice

Wang

et al. 2018

Front. Behav. Neurosci.

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Mounting evidence shows that chronic stress can affect both the structure and function of the brain resulting in decreased synaptic plasticity and cognitive dysfunction. Although several studies have indicated that aged brains are more vulnerable to chronic stress, it remains unknown how to prevent stress-induced memory deficits in aged animals. Neuroinflammation plays an important role in the pathogenesis of chronic stress-related brain dysfunction. Receptor-interacting protein 1 (RIP1) is a key molecule that can modulate inflammation, apoptosis, and necroptosis. Here, we investigated whether inhibiting RIP1 using necrostatin-1 during chronic stress could improve chronic stress-related brain dysfunction in D-galactose-induced aging mice. The stressed mice underwent restraint stress for 14 days. Necrostatin-1 (6.25 mg/kg) or vehicle was administered intraperitoneally once every 3 days during the stress period. Locomotor activity was tested using the open field test and cognitive function was assessed using the novel object recognition and Barnes maze tests. The hippocampus was collected to assess neuroinflammation (Iba1, IL-1α, IL-1β, TNF-α, and C1q), necroptosis [RIP1, RIP3, mixed lineage kinase domain-like (MLKL), and NF-κB], neuroplasticity (doublecortin, NR1, NR2A, NR2B, GluA1, and GluA2), and the expression of glucocorticoid and mineralocorticoid receptors. Blood samples were collected to quantify the levels of corticosterone. We found that chronic stress induced obvious memory impairment and neuroinflammation, decreased neurogenesis and GluA2 expression, and increased the expression of RIP1 and NF-κB. Inhibiting RIP1 by necrostatin-1 during chronic stress rescued the memory impairment and alleviated the pathological changes induced by stress. These suggest that inhibiting RIP1 using necrostatin-1 improves chronic stress-related brain dysfunction in D-galactose-induced aging mice. The potential mechanisms include limitation of neuroinflammation and the rescue of neurogenesis and GluA2 expression.

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“…In 2017, Briz et al confirmed that a BC1 deficiency causes expression imbalances in the postsynaptic region, promoting an abnormal expression of glutamate receptor subunits that results in excessive signal transmission. The resulting hyperexcitation of neurons extinguishes synaptic plasticity, leading to severe defects in cognition and learning [62].…”

Section: Functions Of Bc Rnasmentioning

confidence: 99%

Brain Cytoplasmic RNAs in Neurons: From Biosynthesis to Function

Lee

Kim

et al. 2020

Biomolecules

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Flexibility in signal transmission is essential for high-level brain function. This flexibility is achieved through strict spatial and temporal control of gene expression in neurons. Given the key regulatory roles of a variety of noncoding RNAs (ncRNAs) in neurons, studying neuron-specific ncRNAs provides an important basis for understanding molecular principles of brain function. This approach will have wide use in understanding the pathogenesis of brain diseases and in the development of therapeutic agents in the future. Brain cytoplasmic RNAs (BC RNAs) are a leading paradigm for research on neuronal ncRNAs. Since the first confirmation of brain-specific expression of BC RNAs in 1982, their investigation has been an area of active research. In this review, we summarize key studies on the characteristics and functions of BC RNAs in neurons.

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The non-coding RNA BC1 regulates experience-dependent structural plasticity and learning

Cited by 46 publications

References 82 publications

BC RNA Mislocalization in the Fragile X Premutation

BC RNA Mislocalization in the Fragile X Premutation

Inhibiting RIP1 Improves Chronic Stress-Induced Cognitive Impairments in D-Galactose-Induced Aging Mice

Brain Cytoplasmic RNAs in Neurons: From Biosynthesis to Function

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