Article
Biochemistry & Molecular Biology
Florencia Haase, Rachna Singh, Brian Gloss, Patrick Tam, Wendy Gold
Summary: Rett syndrome is a rare disorder that causes intellectual disabilities in females, primarily due to mutations in the MeCP2 gene. The molecular pathways from genotype to phenotype are not yet fully understood. Treatment options for Rett syndrome are limited, and there is a lack of common disease drivers, biomarkers, or therapeutic targets. In this study, a meta-analysis of transcriptomic studies identified a module of genes common to multiple datasets, with ten hub genes driving their expression. These genes have the potential to be therapeutic targets for Rett syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Alba-Aina Castells, Rafel Balada, Alba Tristan-Noguero, Mar O'Callaghan, Elisenda Cortes-Saladelafont, Ainhoa Pascual-Alonso, Angels Garcia-Cazorla, Judith Armstrong, Soledad Alcantara
Summary: This study aims to explore potential biomarkers for Rett syndrome and MECP2 duplication syndrome, and establish a foundation for early diagnosis and monitoring of disease progression. The results suggest the possibility of identifying specific miRNA biomarker panels to aid in stratification of patient groups.
Article
Cell Biology
Xiaoying Chen, Xu Han, Bruno Blanchi, Wuqiang Guan, Weihong Ge, Yong-Chun Yu, Yi E. Sun
Summary: Rett syndrome is a progressive neurodevelopmental disorder caused by MeCP2 mutations, resulting in stable neuronal maturation deficits. Knockdown of MeCP2 leads to more severe neuronal impairments compared to RTT iPSC-derived neurons, which show partial preservation of function. The study also reveals graded sensitivities of neuron-inherent and neural transmission phenotypes towards the extent of MeCP2 deficiency, providing important insights for future therapeutic development.
Article
Biochemistry & Molecular Biology
Paolo Petazzi, Olga Caridad Jorge-Torres, Antonio Gomez, Iolanda Scognamiglio, Jordi Serra-Musach, Angelika Merkel, Daniela Grases, Clara Xiol, Mar O'Callaghan, Judith Armstrong, Manel Esteller, Sonia Guil
Summary: Rett syndrome is a severe neurodevelopmental disease caused by mutations in the MeCP2 gene, which affects synaptic plasticity and neuronal activity. The MeCP2 protein is critical for the proper expression of immediate-early genes (IEGs) involved in activity-dependent responses, and abnormal expression of IEGs is found in MeCP2-deficient neurons and in RTT patients. These findings highlight the importance of IEGs in synaptic development and the regulatory role of MeCP2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Yongxin Wen, Jiaping Wang, Qingping Zhang, Xiaoxu Yang, Liping Wei, Xinhua Bao
Summary: This study investigated the presence of MECP2 germline mosaicism in sperm and blood samples of fathers of girls with Rett syndrome (RTT) and healthy adult males. The results showed that 28.1% of fathers of RTT girls and 28.0% of healthy adult males had MECP2 mosaicism in their sperm samples. Additionally, only one father had MECP2 mosaicism in their blood sample. These findings suggest that germline mosaic mutations of MECP2 in sperm and blood samples may contribute to the inheritance of RTT.
Review
Biochemistry & Molecular Biology
Clara Xiol, Maria Heredia, Ainhoa Pascual-Alonso, Alfonso Oyarzabal, Judith Armstrong
Summary: Rett syndrome (RTT) is a severe neurodevelopmental disorder with great genetic heterogeneity, evolving towards a spectrum of overlapping phenotypes. To achieve fast and accurate genetic diagnosis, simultaneous multiple gene testing and thorough phenotypic characterization are mandatory. Recent technological advancements, such as whole genome sequencing and omics integration, will contribute to increasing diagnostic yield and expanding knowledge on the pathophysiology of these disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Ya-Jie Xu, Pei-Pei Liu, Zhong-Ze Yan, Ting-Wei Mi, Ying-Ying Wang, Qian Li, Zhao-Qian Teng, Chang-Mei Liu
Summary: The study revealed that MECP2 deletion led to reduced neuron numbers and simplified dendritic morphology, while treatment with small molecules KW-2449 and VPA, which activate the PI3K-AKT signaling pathway, could alleviate neuronal deficits in RTT models. These findings suggest that KW-2449 and VPA may be promising drugs for the treatment of Rett syndrome.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Catarina Miranda-Lourenco, Jessica Rosa, Nadia Rei, Rita F. Belo, Ana Luisa Lopes, Diogo Silva, Catia Vieira, Teresa Magalhaes-Cardoso, Ricardo Viais, Paulo Correia-de-Sa, Ana M. Sebastiao, Maria J. Diogenes
Summary: This study reveals significant changes in the BDNF and adenosine signaling pathways in a milder phenotype model of Rett Syndrome, suggesting that enhancing adenosinergic activity may be an effective therapeutic strategy for RTT patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jian Zhou, Hamdan Hamdan, Hari Krishna Yalamanchili, Kaifang Pang, Amy E. Pohodich, Joanna Lopez, Yingyao Shao, Juan A. Oses-Prieto, Lifang Li, Wonho Kim, Mark A. Durham, Sameer S. Bajikar, Donna J. Palmer, Philip Ng, Michelle L. Thompson, E. Martina Bebin, Amelie J. Mueller, Alma Kuechler, Antje Kampmeier, Tobias B. Haack, Alma L. Burlingame, Zhandong Liu, Matthew N. Rasband, Huda Y. Zoghbi
Summary: MeCP2 plays a critical role in Rett syndrome and MECP2 duplication syndrome. It interacts with a transcription factor, TCF20, at the chromatin interface, and together they regulate the expression of neuronal genes. Reduction of TCF20 partially rescues the behavioral deficits caused by MECP2 overexpression. A patient with a mutation in the PHF14 subunit of the TCF20 complex, disrupting the MeCP2-PHF14-TCF20 interaction, exhibits Rett-like neurological features.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Ainhoa Pascual-Alonso, Antonio F. Martinez-Monseny, Clara Xiol, Judith Armstrong
Summary: Mutations in the MECP2 gene can lead to Rett syndrome, primarily affecting females, while males can have a wide range of clinical presentations. In addition, there are unknown variants in MECP2 that complicate diagnosis. Unlike RTT, MECP2 duplication syndrome predominantly affects males and is usually inherited from the mother.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Elena Albizzati, Elena Florio, Federica Miramondi, Irene Sormonta, Nicoletta Landsberger, Angelisa Frasca
Summary: This study investigated the cytoskeletal features of astrocytes in Mecp2 deficient brains and found that Mecp2 deficiency causes structural and molecular alterations in astrocytes. These alterations progress with the severity of symptoms and occur differently in different cerebral regions, highlighting the importance of considering heterogeneity when studying astrocytes in Rett syndrome.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Clinical Neurology
Giorgia Tascini, Giovanni Battista Dell'Isola, Elisabetta Mencaroni, Giuseppe Di Cara, Pasquale Striano, Alberto Verrotti
Summary: Rett Syndrome is a rare and severe X-linked developmental brain disorder that primarily affects females. Sleep disorders are common in individuals with Rett Syndrome and have an impact on their development and families, but evidence for their management is limited.
FRONTIERS IN NEUROLOGY
(2022)
Article
Medicine, Research & Experimental
Linda Scaramuzza, Giuseppina De Rocco, Genni Desiato, Clementina Cobolli Gigli, Martina Chiacchiaretta, Filippo Mirabella, Davide Pozzi, Marco De Simone, Paola Conforti, Massimiliano Pagani, Fabio Benfenati, Fabrizia Cesca, Francesco Bedogni, Nicoletta Landsberger
Summary: MECP2 mutations cause Rett syndrome, affecting females and altering early brain development. Increasing neuronal activity may delay specific RTT phenotypes.
EMBO MOLECULAR MEDICINE
(2021)
Article
Genetics & Heredity
Eugene J. Gardner, Alejandro Sifrim, Sarah J. Lindsay, Elena Prigmore, Diana Rajan, Petr Danecek, Giuseppe Gallone, Ruth Y. Eberhardt, Hilary C. Martin, Caroline F. Wright, David R. FitzPatrick, Helen Firth, Matthew E. Hurles
Summary: Structural variations (SVs) are genetic alterations larger than 50 bp that can lead to genetic diseases, and are often missed by conventional diagnostic methods. By using the InDelible tool, researchers were able to identify rare damaging variants in genes associated with developmental disorders, improving diagnostic yield and potentially expanding understanding of genetic diseases.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Health Care Sciences & Services
Galina Portnova, Anastasia Neklyudova, Victoria Voinova, Olga Sysoeva
Summary: This study compared EEG activity between girls with Rett syndrome and typically developing peers, and identified several EEG parameters that differentiated the groups. Only elevated generalized background slowing and a newly introduced frequency rate index showed significant correlation with Rett syndrome progression and breathing irregularities.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Neurosciences
Xiaomei Lin, Tianyuyi Feng, Erheng Cui, Yunfei Li, Zhang Qin, Xiaohu Zhao
Summary: This study successfully established a rat model based on the genetic-environmental interaction, which exhibited phenotype characteristics similar to human AD in terms of cognitive function, brain microstructure, and immunohistochemistry. The genetic factor (APP mutation) and the environmental factor (acrolein exposure) accounted for 39.74% and 33.3% of the AD-like phenotypes in the model, respectively.
Article
Neurosciences
Gustavo Guimara Guerrero, Giovanna Bignoto Minhoto, Camilla dos Santos Tiburcio-Machado, Itza Amarisis Ribeiro Pinto, Claudio Antonio Federico, Marcia Carneiro Valera
Summary: The present study evaluated the influence of head and neck radiotherapy on the behavior and body weight gain in Wistar rats. The results demonstrated that different doses of radiation induced depressive behavior in the animals, and that the weight gain tended to be lower in the irradiated groups.
Article
Neurosciences
Ziwei Gao, Chao Lu, Yaping Zhu, Yuxin Liu, Yuesong Lin, Wenming Gao, Liyuan Tian, Lei Wu
Summary: This study reveals the underlying mechanisms of the rapid antidepressant effects of merazin hydrate (MH), which activates CaMKII to promote neuronal activities and proliferation in the hippocampus.
Article
Neurosciences
Kathleen E. Murray, Whitney A. Ratliff, Vedad Delic, Bruce A. Citron
Summary: Gulf War Illness (GWI) is a chronic disorder that affects approximately 30% of Veterans deployed to the Persian Gulf. This study found that exposure to toxicants during the Gulf War resulted in long-term changes in the morphology of dentate granule cells and that treatment with Nrf2 activator could improve neuronal health in the hippocampus.
Article
Neurosciences
Jing Li, Yan Zou, Xiangchuang Kong, Yangming Leng, Fan Yang, Guofeng Zhou, Bo Liu, Wenliang Fan
Summary: This study examines the functional connectivity changes in individuals with sudden sensorineural hearing loss (SSNHL) at the integrity, network, and edge levels. The findings reveal reduced intranetwork connectivity strength and increased internetwork connectivity in SSNHL patients. These alterations are associated with the duration of SSNHL and Tinnitus Handicap Inventory scores. The study provides crucial insights into the neural mechanisms of SSNHL and the brain's network-level responses to sensory loss.
Review
Neurosciences
Didier Majou, Anne-Lise Dermenghem
Summary: In the early stages of SAD, memory impairment is strongly correlated with cortical levels of soluble amyloid-beta peptide oligomers. A beta disrupts glutamatergic synaptic function and leads to cognitive deficits. This article describes the pathogenic mechanisms underlying cerebral amyloidosis, involving amyloid precursor protein synthesis, A beta residue clearance processes, and the role of specific molecules.
Article
Neurosciences
Jing Li, Yi Shan, Xiaojing Zhao, Guixiang Shan, Peng-Hu Wei, Lin Liu, Changming Wang, Hang Wu, Weiqun Song, Yi Tang, Guo-Guang Zhao, Jie Lu
Summary: This study investigates changes in brain anatomical structures and functional network connectivity after chronic complete thoracic spinal cord injury (cctSCI) and their impact on clinical outcomes. The findings reveal alterations in gray matter volume and functional connectivity in specific brain regions, indicating potential therapeutic targets and methods for tracking treatment outcomes.
Article
Neurosciences
Anllely Fernandez, Katherine Corvalan, Octavia Santis, Maxs Mendez-Ruette, Ariel Caviedes, Matias Pizarro, Maria -Teresa Gomez, Luis Federico Batiz, Peter Landgraf, Thilo Kahne, Alejandro Rojas-Fernandez, Ursula Wyneken
Summary: This study reveals the importance of SUMOylation in modulating the protein cargo of astrocyte-derived small extracellular vesicles (sEVs) and its potential impact on neurons.
Article
Neurosciences
Anika Luettig, Stefanie Perl, Maria Zetsche, Franziska Richter, Denise Franz, Marco Heerdegen, Ruediger Koehling, Angelika Richter
Summary: This study found that changes in c-Fos activity during short-term stimulation of the entopeduncular nucleus (EPN) are associated with improvement in dystonia, and also discovered that the cerebellum may be involved in the antidystonic effects.
Article
Neurosciences
Yanlin Tao, Wei Shen, Houyuan Zhou, Zikang Li, Ting Pi, Hui Wu, Hailian Shi, Fei Huang, Xiaojun Wu
Summary: Depression has a higher incidence in women compared to men, and this study investigated the impact of sex on depressive behaviors and underlying mechanisms using a corticosterone-induced depression model in mice. The results showed sex-specific anxiety and depression behaviors in the model group, as well as differences in protein expression and neurotransmitter levels between male and female mice. These findings enhance our understanding of sex-specific differences in depression and support tailored interventions.
Review
Neurosciences
Dnyandev G. Gadhave, Vrashabh V. Sugandhi, Chandrakant R. Kokare
Summary: This article discusses the characteristics and importance of the tight junctions of endothelial cells in the CNS, which act as a biological barrier known as the blood-brain barrier (BBB). It focuses on overcoming the challenges of delivering therapeutic agents to the brain in neurodegenerative disorders, particularly multiple sclerosis, through the use of biomaterials. The article also highlights the current limitations of animal models for studying multiple sclerosis and suggests a potential future research direction.
Article
Neurosciences
Li-Min Mao, Khyathi Thallapureddy, John Q. Wang
Summary: Propofol can enhance synapsin phosphorylation and modulate synaptic transmission in the mouse brain. The study reveals the potential role of synapsin as a substrate of propofol and its effects on neurotransmitter release machinery.
Article
Neurosciences
Syed Maaz Ahmed Rizvi, Abdul Baseer Buriro, Irfan Ahmed, Abdul Aziz Memon
Summary: This study explores the effects of prolonged mask usage on the human brain by analyzing EEG and physiological parameters. The results show that the mean EEG spectral power in alpha, beta, and gamma sub-bands of individuals wearing masks is smaller than those without masks. The performances on cognitive tasks and oxygen saturation level differ between the two groups, while blood pressure, body temperature, and heart rate are similar. The analysis also reveals that the occipital and frontal lobes exhibit the greatest variability in channel measurements.
Article
Neurosciences
Rui-Fang Ma, Lu-Lu Xue, Jin-Xiang Liu, Li Chen, Liu-Lin Xiong, Ting-Hua Wang, Fei Liu
Summary: This study observed changes in brain infarction and blood vessels in rats during neonatal hypoxic ischemic encephalopathy (NHIE) modeling using Transcranial Doppler Ultrasonography (TCD). Longer duration of hypoxia was associated with more severe nerve damage. TCD can dynamically monitor cerebral infarction after NHIE modeling, which may serve as a useful auxiliary method for evaluating animal experimental models.
Article
Neurosciences
Yuxiang Dai, Chen Yu, Lu Zhou, Longyang Cheng, Hongbin Ni, Weibang Liang
Summary: Overexpression of CXCR4 in glioma is correlated with patient survival, and its inhibition can reduce invasion and migration of glioma cells. Inhibiting Nur77 also decreases cancer progression associated with CXCR4.