Lara O Franco, Mário J Carvalho, Jéssica Costa, Pedro A Ferreira, Joana R Guedes, Renato Sousa, Mohamed Edfawy, Catarina M Seabra, Ana L Cardoso, João Peça
Social hierarchies are present in most mammalian species. In nature, hierarchies offer a tradeoff between reduction of in-group fighting between males, at the expense of an asymmetric sharing of resources. Early life experiences and stress are known to influence the rank an individual attains in adulthood, but the associated cellular and synaptic alterations are poorly understood. Using a maternal separation protocol, we show that care-deprived mice display a long-lasting submissive phenotype, increased social recognition, and enhanced explorative behavior...
August 2020: Neuropsychopharmacology
Andjela Markovic, Michael Kaess, Leila Tarokh
Quantifying the degree to which genetic and environmental factors shape brain network connectivity is critical to furthering our understanding of the developing human brain. Sleep, a state of sensory disengagement, provides a unique opportunity to study brain network activity noninvasively by means of sleep electroencephalography (EEG) coherence. We conducted a high-density sleep EEG study in monozygotic (MZ; n = 38; mean age = 12.46; 20 females) and dizygotic (DZ; n = 24; mean age = 12.50; 12 females) twins to assess the heritability of sleep EEG coherence in early adolescence-a period of significant brain rewiring...
June 3, 2020: Cerebral Cortex
Tim L Emmerzaal, Graeme Preston, Bram Geenen, Vivienne Verweij, Maximilian Wiesmann, Elisavet Vasileiou, Femke Grüter, Corné de Groot, Jeroen Schoorl, Renske de Veer, Monica Roelofs, Martijn Arts, Yara Hendriksen, Eva Klimars, Taraka R Donti, Brett H Graham, Eva Morava, Richard J Rodenburg, Tamas Kozicz
Mitochondria play a critical role in bioenergetics, enabling stress adaptation, and therefore, are central in biological stress responses and stress-related complex psychopathologies. To investigate the effect of mitochondrial dysfunction on the stress response and the impact on various biological domains linked to the pathobiology of depression, a novel mouse model was created. These mice harbor a gene trap in the first intron of the Ndufs4 gene (Ndufs4GT/GT mice), encoding the NDUFS4 protein, a structural component of complex I (CI), the first enzyme of the mitochondrial electron transport chain...
June 1, 2020: Translational Psychiatry
Katerina Aravantinou-Fatorou, Dimitra Thomaidou
Direct neuronal reprogramming, rewiring the epigenetic and transcriptional network of a differentiated cell type to neuron, apart from being a very promising approach for the treatment of brain injury and neurodegeneration, also offers a prime opportunity to investigate the molecular underpinnings of neuronal cell fate determination, as the precise molecular mechanisms that establish neuronal fate and diversity at the transcriptional and epigenetic level are incompletely understood. Recent studies from a number of groups, including ours, have shown that astrocytes can be directly reprogrammed into functional neurons in vitro and in vivo following ectopic overexpression of combinations of transcription factors, neurogenic proteins, miRNAs, and small chemical molecules...
2020: Methods in Molecular Biology
Subaramya Srivishagan, A A I Perera, Ali Hojjat, Nagulan Ratnarajah
BACKGROUND: The nodal brain network measures (e.g. centrality measures) are defined for a single node and the global network measures (e.g. global efficiency) are defined for the whole brain in the literature. But a meaningful group of nodes will be benefited from a formulation that applies to a group of nodes rather than a single node or the whole brain. The question like "which brain-lobe is more structurally central in the older-adult brain?" could be answered to some extent by the application of a centrality measure that applied to the group of nodes from each lobe...
May 27, 2020: Brain Connectivity
Takashi Tanaka, Tetsufumi Ito, Megumi Sumizono, Munenori Ono, Nobuo Kato, Satoru Honma, Masaki Ueno
Background . Brain injury often causes severe motor dysfunction, leading to difficulties with living a self-reliant social life. Injured neural circuits must be reconstructed to restore functions, but the adult brain is limited in its ability to restore neuronal connections. The combination of molecular targeting, which enhances neural plasticity, and rehabilitative motor exercise is an important therapeutic approach to promote neuronal rewiring in the spared circuits and motor recovery. Objective . We tested whether genetic reduction of Src homology 2-containing phosphatase-1 (SHP-1), an inhibitor of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, has synergistic effects with rehabilitative training to promote reorganization of motor circuits and functional recovery in a mouse model of brain injury...
May 22, 2020: Neurorehabilitation and Neural Repair
Shuang Chen, Qin Zou, Kui Wang, Yongmin Chen, Xi Kuang, Wengang Wu, Meiwen Guo, Yi Cai, Qifu Li
SPARC (secreted protein acidic and rich in cysteine) family of proteins is a class of protein involved in tissue development and repair by regulating cell adhesion, proliferation, metastasis, and growth factor signaling to affect the extracellular matrix (ECM) and interactions between cells. Although being highly valued in non-nerve tissues, studies in both cell and animal models have been revealed that SPARC family proteins may also continue to play a vital role in central nervous system (CNS) diseases and development...
May 14, 2020: Brain Research Bulletin
Yu-Hui Lin, Meng-Cheng Yao, Hai-Yin Wu, Jian Dong, Huan-Yu Ni, Xiao-Lin Kou, Lei Chang, Chun-Xia Luo, Dong-Ya Zhu
Environmental enrichment (EE) is a generally accepted strategy to promote stroke recovery and its beneficial effect is positively correlated with neuroplasticity. However, the mechanisms underlying it remain elusive. Histone deacetylase 2 (HDAC2), a negative regulator of neuroplasticity, is upregulated after stroke. Thus, we hypothesized that HDAC2 may participate in EE-mediated stroke recovery. In this study, focal stroke was induced by photothrombosis in male mice exposing to EE or standard housing (SH) conditions...
May 16, 2020: Journal of Neurochemistry
Taka-Aki Ichu, Alex Reed, Daisuke Ogasawara, Olesya Ulanovskaya, Amanda Roberts, Carlos A Aguirre, Liron Bar-Peled, Jie Gao, Jason Germain, Sabrina Barbas, Kim Masuda, Bruno Conti, Peter Tontonoz, Benjamin F Cravatt
PHARC (polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and cataract) is a human neurological disorder caused by deleterious mutations in the ABHD12 gene, which encodes an integral membrane lyso-phosphatidylserine (lyso-PS) lipase. Pharmacological or genetic disruption of ABHD12 leads to higher levels of lyso-PS lipids in human cells and the central nervous system (CNS) of mice. ABHD12 loss also causes rapid rewiring of PS content, resulting in selective increases in the level of arachidonoyl (C20:4) PS and decreases in the levels of other PS species...
May 4, 2020: Biochemistry
Mar Márquez-Ropero, Eva Benito, Ainhoa Plaza-Zabala, Amanda Sierra
From development to aging and disease, the brain parenchyma is under the constant threat of debris accumulation, in the form of dead cells and protein aggregates. To prevent garbage buildup, the brain is equipped with efficient phagocytes: the microglia. Microglia are similar, but not identical to other tissue macrophages, and in this review, we will first summarize the differences in the origin, lineage and population maintenance of microglia and macrophages. Then, we will discuss several principles that govern macrophage phagocytosis of apoptotic cells (efferocytosis), including the existence of redundant recognition mechanisms ("find-me" and "eat-me") that lead to a tight coupling between apoptosis and phagocytosis...
2020: Frontiers in Immunology
Ashley E Lepack, Craig T Werner, Andrew F Stewart, Sasha L Fulton, Ping Zhong, Lorna A Farrelly, Alexander C W Smith, Aarthi Ramakrishnan, Yang Lyu, Ryan M Bastle, Jennifer A Martin, Swarup Mitra, Richard M O'Connor, Zi-Jun Wang, Henrik Molina, Gustavo Turecki, Li Shen, Zhen Yan, Erin S Calipari, David M Dietz, Paul J Kenny, Ian Maze
Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from the rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found that histone H3 glutamine 5 dopaminylation (H3Q5dop) plays a critical role in cocaine-induced transcriptional plasticity in the midbrain. Rats undergoing withdrawal from cocaine showed an accumulation of H3Q5dop in the VTA...
April 10, 2020: Science
Ilias Rentzeperis, Cees van Leeuwen
Activity-dependent plasticity refers to a range of mechanisms for adaptively reshaping neuronal connections. We model their common principle in terms of adaptive rewiring of network connectivity, while representing neural activity by diffusion on the network: Where diffusion is intensive, shortcut connections are established, while underused connections are pruned. In binary networks, this process is known to steer initially random networks robustly to high levels of structural complexity, reflecting the global characteristics of brain anatomy: modular or centralized small world topologies...
April 8, 2020: Scientific Reports
Willianne I M Vonk, T Kelly Rainbolt, Patrick T Dolan, Ashley E Webb, Anne Brunet, Judith Frydman
Neural stem and progenitor cells (NSPCs) are critical for continued cellular replacement in the adult brain. Lifelong maintenance of a functional NSPC pool necessitates stringent mechanisms to preserve a pristine proteome. We find that the NSPC chaperone network robustly maintains misfolded protein solubility and stress resilience through high levels of the ATP-dependent chaperonin TRiC/CCT. Strikingly, NSPC differentiation rewires the cellular chaperone network, reducing TRiC/CCT levels and inducing those of the ATP-independent small heat shock proteins (sHSPs)...
March 30, 2020: Molecular Cell
Maheen Mausoof Adamson
Devices in and out of the brain that can stimulate the nervous system through electric current are now being used to treat depression, movement disorders, and chronic pain. Our author, a Stanford School of Medicine clinical associate professor who is senior scientific research director for Defense and Veterans Brain Injury Center at the VA Palo Alto Health Care System, provides insight on the many neuromodulation strategies now available to treat brain injury and the potential of further research to accomplish much more ...
November 2019: Cerebrum: the Dana Forum on Brain Science
E A Koops, R J Renken, C P Lanting, P van Dijk
Neural plasticity due to hearing loss results in tonotopic map changes. Several studies have suggested a relation between hearing-loss-induced tonotopic reorganization and tinnitus. This large functional magnetic resonance imaging (fMRI) study on humans intended to clarify the relations between hearing loss, tinnitus and tonotopic reorganization. To determine the differential effect of hearing loss and tinnitus, both male and female participants with bilateral high frequency hearing loss, with and without tinnitus, and a control group were included...
March 13, 2020: Journal of Neuroscience
Tanu Wadhera, Deepti Kakkar
Methods : Thirty individuals with ASD (11-18years) and thirty Typically Developing (TD) individuals (11-16years) were recruited to perform the mental task. The participants were instructed to flip the shown geometric images mentally and mark their response on a scale. The task-related multivariate EEG activations were analyzed using multiplex temporal Visibility Graphs (VGs) to compute local and global brain network functional connectivity dynamics. Results : With cognitive load (0-back to the 2-back task), the behavioral performance (d' index and Reaction Time) has reduced in ASD...
March 4, 2020: Neurological Research
Júlia Pinho, Cristina Marcut, Rosalina Fonseca
Activity-dependent plasticity of synaptic connections is a hallmark of the mammalian brain and represents a key mechanism for rewiring neural circuits during development, experience-dependent plasticity, and brain disorders. Cellular models of memory, such as long-term potentiation and long-term depression, share common principles to memory consolidation. As for memory, the maintenance of synaptic plasticity is dependent on the synthesis of de novo protein synthesis. The synaptic-tagging and capture hypothesis states that the maintenance of synaptic plasticity is dependent on the interplay between input-specific synaptic tags and the allocation or capture of plasticity-related proteins (PRPs) at activated synapses...
February 20, 2020: IUBMB Life
Maria E Barnes-Davis, Brady J Williamson, Stephanie L Merhar, Scott K Holland, Darren S Kadis
Children born preterm are at increased risk for cognitive impairment, with higher-order functions such as language being especially vulnerable. Previously, we and others have reported increased interhemispheric functional connectivity in children born extremely preterm; the finding appears at odds with literature showing decreased integrity of the corpus callosum, the primary commissural bundle, in preterm children. We address the apparent discrepancy by obtaining advanced measures of structural connectivity in twelve school-aged children born extremely preterm (<28 weeks) and ten term controls...
January 22, 2020: NeuroImage: Clinical
Shi-Chun Bao, Ahsan Khan, Rong Song, Raymond Kai-Yu Tong
Electrical stimulation has been extensively applied in post-stroke motor restoration, but its treatment mechanisms are not fully understood. Stimulation of neuromotor control system at multiple levels manipulates the corresponding neuronal circuits and results in neuroplasticity changes of stroke survivors. This rewires the lesioned brain and advances functional improvement. This review addresses the therapeutic mechanisms of different stimulation modalities, such as noninvasive brain stimulation, peripheral electrical stimulation, and other emerging techniques...
January 2020: Journal of Stroke
Bas Castelijns, Mirna L Baak, Ilia S Timpanaro, Caroline R M Wiggers, Marit W Vermunt, Peng Shang, Ivanela Kondova, Geert Geeven, Valerio Bianchi, Wouter de Laat, Niels Geijsen, Menno P Creyghton
Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees...
January 16, 2020: Nature Communications
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