Article
Multidisciplinary Sciences
Jamal B. Williams, Qing Cao, Wei Wang, Young-Ho Lee, Luye Qin, Ping Zhong, Yong Ren, Kaijie Ma, Zhen Yan
Summary: The study by Williams et al demonstrates that targeting the aberrant histone modifying enzyme Smyd3 has the potential to rescue NMDAR and cognitive deficits in a mouse model of Alzheimer's disease, highlighting the potential of epigenetic treatment in neurodegenerative diseases.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Wenche Stensen, Ulli Rothweiler, Richard Alan Engh, Melissa R. Stasko, Ilya Bederman, Alberto C. S. Costa, Anders Fugelli, John S. Mjoen Svendsen
Summary: Down syndrome is a complex genetic disorder with substantial physical, cognitive, and behavioral challenges. While treatment options for physical co-morbidities have improved, cognitive deficits in individuals with DS cannot be addressed pharmacologically, and all individuals with DS develop early onset Alzheimer's disease pathology by the age of 40. The study introduces a novel inhibitor for the protein kinase DYRK1A, which is a key controlling kinase associated with DS.
Article
Biotechnology & Applied Microbiology
Martina Parrini, Shovan Naskar, Micol Alberti, Ilaria Colombi, Giovanni Morelli, Anna Rocchi, Marina Nanni, Federica Piccardi, Severine Charles, Giuseppe Ronzitti, Federico Mingozzi, Andrea Contestabile, Laura Cancedda
Summary: Reducing NKCC1 expression by RNA interference restores intracellular chloride concentration and GABA-mediated inhibition in the Ts65Dn mouse model of Down syndrome, leading to improvement in neuronal network dynamics, while AAV-mediated NKCC1 knockdown rescues cognitive deficits in diverse behavioral tasks in these animals. These results establish a mechanistic link between NKCC1 expression and behavioral abnormalities in DS mice, providing a molecular target for new therapeutic approaches such as gene therapy.
Article
Cell Biology
Maria Martinez de Lagran, Aleix Elizalde-Torrent, Roger Paredes, Bonaventura Clotet, Mara Dierssen
Summary: Elevated activity of retrotransposons is associated with various neurodegenerative and neurodevelopmental diseases. This study treated a mouse model of Down syndrome with a reverse transcriptase inhibitor and observed significant improvement in neurobehavioral phenotypes and complete recovery of hippocampal-dependent recognition memory.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Neurosciences
Xuechun Cai, Lili Qiu, Chaoran Wang, Hang Yang, Zhenhui Zhou, Meng Mao, Yunqing Zhu, Yazhou Wen, Wenlan Cai, Wei Zhu, Jie Sun
Summary: The alpha 5-containing GABA(A) receptors (GABA(A)Rs-alpha 5) play a crucial role in chronic neuropathic pain-induced cognitive impairment by weakening inhibitory synaptic transmission. Inhibition of GABA(A)Rs-alpha 5 can rescue weakened inhibitory synaptic transmission and cognitive impairment caused by chronic neuropathic pain.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Robin Scharrenberg, Melanie Richter, Ole Johanns, Durga Praveen Meka, Tabitha Ruecker, Nadeem Murtaza, Zsuzsa Lindenmaier, Jacob Ellegood, Anne Naumann, Bing Zhao, Birgit Schwanke, Jan Sedlacik, Jens Fiehler, Ileana L. Hanganu-Opatz, Jason P. Lerch, Karun K. Singh, Froylan Calderon de Anda
Summary: This study demonstrates the essential role of the Taok2 gene in neuronal migration, particularly the impact of de novo mutations associated with ASD on migration, and highlights the critical role of Taok2 in cortical development.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Stamatina Tzanoulinou, Stefano Musardo, Alessandro Contestabile, Sebastiano Bariselli, Giulia Casarotto, Elia Magrinelli, Yong-hui Jiang, Denis Jabaudon, Camilla Bellone
Summary: Mutations in the SHANK3 gene have been identified as a genetic risk factor for Autism Spectrum Disorder (ASD). This study demonstrates that region-specific downregulation of Shank3 in neonatal mice leads to hyperexcitability of certain neurons and impairs social behavior. Furthermore, acute inhibition of Trpv4 can rescue these behavioral deficits.
MOLECULAR PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Anna A. Cook, Sriram Jayabal, Jacky Sheng, Eviatar Fields, Tsz Chui Sophia Leung, Sabrina Quilez, Eileen McNicholas, Lois Lau, Shixia Huang, Alanna J. Watt
Summary: In a mouse model of SCA6, exercise and the TrkB agonist 7,8-DHF were found to increase cerebellar BDNF expression, improve motor coordination and cerebellar cell firing rate deficits, suggesting their potential as therapeutic interventions for SCA6.
Article
Neurosciences
Guoli Wang, Ying Liu, Xuejie Zhu, Kehao Lin, Mingkai Li, Zhenke Wu, Ronghua Zhang, Qiusheng Zheng, Defang Li, Tianyue An
Summary: This study demonstrates that miR-134-5p regulates dendritic deficits in depression by promoting AMPK-mediated mitophagy, providing a potential new target for antidepressant drug research and development.
Article
Neurosciences
Jovana Arandelovic, Anja Santrac, Bojan Batinic, Lidija Todorovic, Vladimir Stevanovic, Veera Venkata Naga Phani Babu Tiruveedhula, Dishary Sharmin, Farjana Rashid, Boban Stanojevic, James M. Cook, Miroslav M. Savic
Summary: The aim of this study was to assess the effects of negative and positive allosteric modulators of alpha 5 GABA(A) receptors on behavior and neuroinflammation in a widely used Alzheimer's disease (AD) model. The results showed that these modulators had some effects on the behavior and neuroinflammation of transgenic mice, but did not achieve the expected beneficial effects.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Neurosciences
Karim S. Ibrahim, Salah El Mestikawy, Khaled S. Abd-Elrahman, Stephen S. G. Ferguson
Summary: Huntington's disease (HD) is a neurodegenerative disease characterized by motor and cognitive impairments. The role of vesicular glutamate transporter-3 (VGLUT3) in HD pathophysiology is unclear. This study found that VGLUT3 deletion rescued motor and cognitive deficits in HD mouse models, likely through the activation of Akt and ERK1/2 pathways. These findings suggest that VGLUT3 could be a potential target for HD therapeutics.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Yuying Zhang, Xiaojuan Cheng, Luyan Wu, Juan Li, Changyun Liu, Mingjia Wei, Chaofeng Zhu, Huapin Huang, Wanhui Lin
Summary: Inhibition of S6K1 can alleviate seizures and depression, restore power at low frequencies, and correct synaptic and dendritic abnormalities. This finding suggests that inhibiting S6K1 may be a potential target for the treatment of epilepsy.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Jeffrey S. Burgdorf, Sehyoun Yoon, Marc Dos Santos, Catherine R. Lammert, Joseph R. Moskal, Peter Penzes
Summary: We developed a peptide fragment JB2 that promotes synaptic plasticity and has therapeutic potential for Phelan-McDermid Syndrome and Autism Spectrum Disorder (ASD).
MOLECULAR PSYCHIATRY
(2023)
Article
Immunology
Xiaowen Bi, Baolin Jiang, Jinyi Zhou, Xirui Fan, Xintong Yan, Juanjuan Liang, Lan Luo, Zhimin Yin
Summary: Inhibition of CBP bromodomain effectively blocks HMGB1-mediated inflammatory responses and reduces its pro-inflammatory activity. SGC-CBP30 down-regulates the activation of relevant signaling pathways to decrease the inflammatory effects of HMGB1.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Mengjun Zhong, Rili Gao, Ruocong Zhao, Youxue Huang, Cunte Chen, Kehan Li, Xibao Yu, Dingrui Nie, Zheng Chen, Xin Liu, Zhuandi Liu, Shaohua Chen, Yuhong Lu, Zhi Yu, Liang Wang, Peng Li, Chengwu Zeng, Yangqiu Li
Summary: The BET inhibitor JQ1 was found to inhibit the expression of PD-1 in T cells and enhance anti-leukemia immunity. JQ1 also suppressed the growth of AML cells and prolonged survival in mouse models.
CELL DEATH & DISEASE
(2022)
Article
Pharmacology & Pharmacy
Eva Florensa-Zanuy, Emilio Garro-Martinez, Albert Adell, Elena Castro, Alvaro Diaz, Angel Pazos, Karina S. Mac-Dowell, David Martin-Hernandez, Fuencisla Pilar-Cuellar
Summary: Recent evidence suggests that cannabidiol (CBD) has antidepressant properties in a neuroinflammatory model of depression, reducing inflammatory mediators and the activation of specific pathways.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Neurosciences
Veronica Vidal, Susana Garcia-Cerro, Noemi Rueda, Alba Puente, Renata Bartesaghi, Carmen Martinez-Cue
Summary: The study aimed to evaluate the ability of oleic and linolenic acid to restore the defects in neurogenesis and synaptogenesis in the early postnatal stages of a mouse model of Down syndrome. The results suggest that early administration of oleic acid could alleviate the cognitive deficits in individuals with Down syndrome.
NUTRITIONAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Alba Puente-Bedia, Maria T. Berciano, Olga Tapia, Carmen Martinez-Cue, Miguel Lafarga, Noemi Rueda
Summary: Down syndrome is characterized by cognitive impairments, which may be due to defective neurogenesis and abnormal neuronal populations. In the TS mouse model of DS, the triplication of Hsa21 orthologous genes leads to alterations in the nuclear architecture of hippocampal granular cells, potentially contributing to cognitive dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Josep Amigo, Emilio Garro-Martinez, Rebeca Vidal Casado, Valerie Compan, Fuencisla Pilar-Cuellar, Angel Pazos, Alvaro Diaz, Elena Castro
Summary: The study investigated the influence of 5-HT(4)Rs on the response to antidepressant fluoxetine in mice subjected to chronic corticosterone administration. The results indicated that the absence of 5-HT4Rs did not affect the behavioral effects of chronic fluoxetine treatment in a depression and anxiety animal model. Additionally, chronic fluoxetine treatment increased BDNF mRNA expression and potentiated 5-HT1AR desensitization in the corticosterone model.
ACS CHEMICAL NEUROSCIENCE
(2021)
Review
Anatomy & Morphology
Carlos I. Lorda-Diez, Cristina Duarte-Olivenza, Juan M. Hurle, Juan A. Montero
Summary: TGFβ plays a crucial role in embryonic development, particularly in digit formation. Through modern mouse genetic experiments and classical embryological approaches in chick embryos, valuable insights have been gained into the role of TGFβ in the morphogenesis of digits in tetrapods.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Cell Biology
Cristina Sanchez-Fernandez, Carlos I. Lorda-Diez, Cristina Duarte-Olivenza, Juan M. Hurle, Juan A. Montero
Summary: The epigenetic profile of the interdigital mesoderm in vertebrates with free digits may contribute to the sensitivity to DNA damage and apoptosis during tissue regression. This involves a massive degeneration process preceded by intense DNA damage, DNA repair response activation, histone modifications, and histone deacetylase expression.
Article
Biochemistry & Molecular Biology
Juan A. Montero, Carlos Ignacio Lorda-Diez, Juan M. Hurle
Summary: This paper proposes a new perspective on the regulation of programmed cell death (PCD) in developing systems based on epigenetics. It challenges the traditional view that PCD is solely controlled by specific gene-encoded signals, arguing that the signals and local tissue interactions responsible for embryonic tissue growth and differentiation play a significant role in PCD. The study suggests that cells retain an epigenetic profile sensitive to DNA damage, resulting in their subsequent elimination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Nutrition & Dietetics
Carmen Martinez-Cue, Renata Bartesaghi
Summary: Down syndrome (DS) is a genetic disorder caused by the triplication of chromosome 21, resulting in intellectual disability starting in utero and continuing through infancy, with associated impairments in neurogenesis and connectivity that may lead to early-onset Alzheimer's disease. Current research focuses on using DS mouse models to discover potential pharmacotherapies, with fatty acids emerging as a promising treatment option for DS-related cognitive deficits and neurodevelopmental impairments. This suggests a need for further exploration of the potential benefits of fatty acids for individuals with DS.
Review
Psychology, Developmental
Nathalia Garrido-Torres, Karem Guzman-Torres, Susana Garcia-Cerro, Gladys Pinilla Bermudez, Claudia Cruz-Baquero, Hansel Ochoa, Diego Garcia-Gonzalez, Manuel Canal-Rivero, Benedicto Crespo-Facorro, Miguel Ruiz-Veguilla
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social interaction deficiencies, restricted interests, and repetitive behaviors. MicroRNAs (miRs/miRNAs) are implicated in the development of ASD, with miR-451a being the most relevant marker for impaired social interaction. Other dysregulated miRNAs, such as miR-19a-3p, miR-494, and miR-142-3p, are expressed differently in various tissues and body fluids of ASD patients, suggesting their potential as biomarkers. Saliva is considered the optimal biological fluid for miRNA measurements due to its easy collection from children.
EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
(2023)
Article
Pediatrics
Nathalia Garrido-Torres, Lucas Cerrillos, Susana Garcia Cerro, Alberto Perez Gomez, Manuel Canal-Rivero, Beatriz de Felipe, Luis Alameda, Renata Marques Rodriguez, Sergio Anillo, Julia Praena, Cristina Duque Sanchez, Cristina Roca, Maria Paniagua, Alvaro Lopez Diaz, Rafael Romero-Garcia, Peter Olbrich, Martin de Porres Puertas Albarracin, Pablo Reguera Pozuelo, Irene Lujan Sosa, Maria Begona Moreno Duenas, Rocio Pineda Cachero, Lidia Zamudio Juan, Veronica Garcia Rumi, Mercedes Guerrero Benitez, Rosario Figueroa, Antonio Manuel Martin Rendon, Antonio Partida, Maria Isabel Rodriguez Cocho, Carmen Gallardo Trujillo, Isabel Gallego Jimenez, Sarah Garcia Spencer, Marta Gomez Verdugo, Cintia Bermejo Fernandez, Maria Perez Benito, Rafael Esteban Castillo Reina, Angela Cejudo Lopez, Candela Sanchez Tomas, Maria Angeles Chacon Gamero, Ana Rubio, Amanda Moreno Mellado, Victor Ramos Herrero, Ella Starr, Marta Gonzalez Fernandez de Palacios, Elena Garcia Victori, Antonio Pavon Delgado, Ismael Fernandez Cuervo, Alejandro Arias Ruiz, Irene Esperanza Menendez Gil, Ines Dominguez Gomez, Itziar Coca Mendoza, Rosa Ayesa-Arriola, Lourdes Fananas, Juan C. Leza, Jose M. Cisneros, Javier Sanchez Cespedes, Ezequiel Ruiz-Mateos, Benedicto Crespo-Facorro, Miguel Ruiz-Veguilla
Summary: The COVID-19 pandemic provides an important opportunity for studying the pathophysiological mechanisms of neuropsychiatric diseases. This study focuses on investigating the relationship between inflammation, brain development, and the increased risk of neuropsychiatric disorders in newborns with prenatal SARS-CoV-2 infection. The study involves monitoring pregnant women and collecting biological samples before and after childbirth. The findings from this study will contribute to our understanding of the impact of COVID-19 on maternal and newborn health.
FRONTIERS IN PEDIATRICS
(2022)
Article
Cell Biology
Cristina Duarte-Olivenza, Juan M. Hurle, Juan A. Montero, Carlos I. Lorda-Diez
Summary: This study aimed to analyze whether regulated cell degeneration accompanies the differentiation of embryonic limb skeletal progenitors. The results showed that the formation of primary cartilage nodules involves a patterned process of cell death and cell senescence. Furthermore, FGF signaling was found to modulate the response of progenitors to cell death pathways through the positive regulation of apoptosis and cell senescence.
Article
Biochemistry & Molecular Biology
Alba Puente-Bedia, Maria T. Berciano, Carmen Martinez-Cue, Miguel Lafarga, Noemi Rueda
Summary: Hippocampal granule cells in Ts65Dn mice exhibit important oxidative stress-associated alterations, including DNA damage, abnormalities in the proteasome and lysosomal systems, and mitochondrial structural defects. These changes may contribute to cellular senescence, accelerated aging, neurodegenerative diseases, and early development of Alzheimer's pathology.
Article
Immunology
Cristina Duarte-Olivenza, Juan Antonio Montero, Carlos Ignacio Lorda-Diez
Summary: The study revealed the dual and opposite effects of berberine on the growth and differentiation of skeletal progenitors, showing an inhibitory or promoting effect on chondrogenesis depending on the stage of culture. Furthermore, berberine may be involved in cartilage differentiation through transcriptional influence on DNA methyltransferase genes, suggesting the potential role of epigenetic factors in its effects. These findings have important implications for the clinical use of berberine in the treatment of cartilage degenerative diseases.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Philosophy
Juan Antonio Cabrera Montero
Summary: In the fourth treatise, Boethius offers a confession of faith inspired by the Augustinian theological tradition. This work stands out from his others due to the use of Scripture as a guiding thread and the exposition of fundamental contents of Christian faith in a more personal and vital manner. It presents a different perspective on the fundamental aspects of Christian faith, with a diverse, technical method.
RIVISTA DI FILOSOFIA NEO-SCOLASTICA
(2021)