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Brain methylome remodeling selectively regulates neuronal activity genes linking to emotional behaviors in mice exposed to maternal immune activation
How early life experience impacts adult behavior is unclear. Here, authors show that maternal immune activation remodels mouse brain methylome and selectively regulates neuronal activity genes, resulting in anxiety- and depression-like behaviors.
- Li Ma
- , Feng Wang
- & Jian-Fu Chen
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Article
| Open Access
Epigenetic regulation of beta-endorphin synthesis in hypothalamic arcuate nucleus neurons modulates neuropathic pain in a rodent pain model
Neuropathic pain is a complex and often disabling condition with unclear pathogenesis. Here, the authors elucidate an epigenetic regulatory pathway driven by microRNA regulation of betaendorphin (β-EP) synthesis in the hypothalamic arcuate nucleus (ARC) neurons to modulate neuropathic pain.
- Yu Tao
- , Yuan Zhang
- & Jin Tao
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Article
| Open Access
Inhibition of histone methyltransferase Smyd3 rescues NMDAR and cognitive deficits in a tauopathy mouse model
The study by Williams et al shows targeting the aberrant histone modifying enzyme Smyd3 rescues NMDAR and cognitive deficits in a mouse model of Alzheimer’s disease. It highlights the potential of epigenetic treatment in neurodegenerative diseases.
- Jamal B. Williams
- , Qing Cao
- & Zhen Yan
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Article
| Open Access
Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome
The molecular mechanisms underlying deficits in Down syndrome remain unclear. Here, the authors show that copy number restoration of a chromatin remodeler in trisomic mice is sufficient to rescue epigenomic, physiological and cognitive deficits.
- Sasha L. Fulton
- , Wendy Wenderski
- & Ian Maze
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Article
| Open Access
Organic anion transporter 1 is an HDAC4-regulated mediator of nociceptive hypersensitivity in mice
Chronic pain is sustained by alterations in gene transcription. Here, the authors show that increased expression of Organic Anionic Transporter 1 in the spinal cord is epigenetically controlled and key to hypersensitivity in pathological pain.
- Christian Litke
- , Anna M. Hagenston
- & Daniela Mauceri
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Article
| Open Access
Neuronal Yin Yang1 in the prefrontal cortex regulates transcriptional and behavioral responses to chronic stress in mice
The mechanisms underlying the chronic stress-induced increased risk for major depressive disorder and anxiety are unclear. Here, the authors show the transcriptional changes occurring in neocortical neurons and identify YY1 as a regulator of chronic stress-induced maladaptive behavior in mice.
- Deborah Y. Kwon
- , Bing Xu
- & Zhaolan Zhou
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Article
| Open Access
Neuronal Nsun2 deficiency produces tRNA epitranscriptomic alterations and proteomic shifts impacting synaptic signaling and behavior
The link between tRNA modifications, protein translation, and behavior is unclear. Here, the authors show that neuronal Nsun2 deficiency results in codon-specific epitranscriptomic changes of Gly-tRNAs and proteomic changes affecting synaptic signaling and behavior in mice.
- J. Blaze
- , A. Navickas
- & S. Akbarian
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Article
| Open Access
Environmental enrichment preserves a young DNA methylation landscape in the aged mouse hippocampus
Decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Here the authors provide evidence that environmental enrichment delays age-related DNA methylation alterations in the mouse hippocampus.
- Sara Zocher
- , Rupert W. Overall
- & Gerd Kempermann
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Article
| Open Access
Common schizophrenia risk variants are enriched in open chromatin regions of human glutamatergic neurons
Here, the authors perform ATAC-seq on four distinct cell populations from three different regions of the human brain, finding that chromatin accessibility varies greatly by cell type and less by brain region. This study reveals differences in biological function and gene regulation, as well as overlap of genetic variants associated with schizophrenia and other neuropsychiatric traits.
- Mads E. Hauberg
- , Jordi Creus-Muncunill
- & Panos Roussos
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Article
| Open Access
Chromatin accessibility mapping of the striatum identifies tyrosine kinase FYN as a therapeutic target for heroin use disorder
Epigenetic mechanisms have emerged as contributors to the molecular impairments caused by exposure to environmental factors such as abused substances. Here the authors perform epigenetic profiling of the striatum and identify the tyrosine kinase FYN is an important driver of neurodegenerative-like pathology and drug-taking behaviour.
- Gabor Egervari
- , Diana Akpoyibo
- & Yasmin L. Hurd
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Article
| Open Access
DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice
AgRP neurons in the hypothalamic arcuate nucleus (ARH) are involved in regulating hunger and energy balance. Here the authors show that knockout of the DNA methyltransferase Dnmt3a in AgRP neurons of the ARH leads to a reduction in voluntary exercise along with numerous epigenetic and gene expression changes in ARH neurons.
- Harry MacKay
- , C. Anthony Scott
- & Robert A. Waterland
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Article
| Open Access
Chromatin organization in the female mouse brain fluctuates across the oestrous cycle
The molecular mechanisms underlying the dynamic nature of the female brain structure and function remain poorly understood. Here the authors characterise chromatin organization in the mouse female ventral hippocampus, finding it fluctuates with the oestrous cycle, and identify changes in chromatin organization associated with the transcription of genes important for neuronal function and behaviour.
- Ivana Jaric
- , Devin Rocks
- & Marija Kundakovic
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Article
| Open Access
Epigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory
Circadian rhythms are known to modulate memory, but it’s not known whether clock genes in the hippocampus are required for memory consolidation. Here, the authors show that epigenetic regulation of clock gene Period1 in the hippocampus regulates memory and contributes to age-related memory decline, independent of circadian rhythms.
- Janine L. Kwapis
- , Yasaman Alaghband
- & Marcelo A. Wood
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Article
| Open Access
Placental miR-340 mediates vulnerability to activity based anorexia in mice
Anorexia nervosa is characterised by self-starvation but its etiology is not completely understood. Here the authors describe how prenatal stress can induce activity-based anorexia in the offspring during early adulthood by upregulating miR-340 expression in the placenta that affects expression of nutrient transporters.
- Mariana Schroeder
- , Mira Jakovcevski
- & Alon Chen
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Article
| Open Access
LSD1 protects against hippocampal and cortical neurodegeneration
“LSD1 is a histone demethylase that plays many roles during development. Here, the authors provide evidence that loss of LSD1 in adult mice leads to paralysis and neurodegeneration in the hippocampus and cortex and suggest a potential link between LSD1 and human neurodegenerative disease.
- Michael A. Christopher
- , Dexter A. Myrick
- & David J. Katz
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Article
| Open Access
Shifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies
Transcriptional regulation is necessary for maintaining long-term memories (LTM) but the mechanistic details are not completely defined. Here the authors identify transcriptional machinery and histone modifiers required for LTM maintenance inDrosophilaand show that transcriptional regulation for LTM maintenance is distinct from that for LTM formation.
- Yukinori Hirano
- , Kunio Ihara
- & Minoru Saitoe
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Article
| Open Access
The microRNA cluster miR-183/96/182 contributes to long-term memory in a protein phosphatase 1-dependent manner
Protein phosphatase1 (PP1), a signalling and transcriptional regulator, and epigenetic modulator is known to be a memory suppressor. Here the authors show that memory control by PP1 involves the microRNA cluster miR-183/96/182, and that this cluster is selectively regulated during memory formation in mice.
- Bisrat T. Woldemichael
- , Ali Jawaid
- & Isabelle M. Mansuy
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Article
| Open Access
Behavioural traits propagate across generations via segregated iterative-somatic and gametic epigenetic mechanisms
Physiological effects of psychological stress and infection in mothers can increase the incidence of anxiety and psychiatric diseases in offsprings and in subsequent generation. Here, Miklos Toth and colleagues show that intergenerational inheritance of neurological traits is propagated across multiple generations independently by parallel non-genetic mechanisms involving independent segregation of epigenetic specific loci.
- Emma Mitchell
- , Shifra L. Klein
- & Miklos Toth
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Early life stress in fathers improves behavioural flexibility in their offspring
Traumatic events in one generation can affect the behaviour of their offspring. Here the authors subject male mouse pups to traumatic stress and find that their offspring display improved goal-directed behaviours associated with epigenetic changes of the mineralocorticoid receptor gene.
- Katharina Gapp
- , Saray Soldado-Magraner
- & Isabelle M. Mansuy
AgRP neuron cis-regulatory analysis across hunger states reveals that IRF3 mediates leptin’s acute effects