Article
Genetics & Heredity
Amy E. Clipperton-Allen, Angela Zhang, Ori S. Cohen, Damon Theron Page
Summary: The study demonstrated that exposing Pten(+/-) mice to environmental enrichment after brain overgrowth occurred can improve their social behavioral deficits and partially ameliorate repetitive behavior deficits. Environmental enrichment restored the abnormal levels of excitatory and inhibitory presynaptic proteins in Pten(+/-) mice.
Article
Medicine, General & Internal
Kartikeya Murari, Abdulrahman Abushaibah, Jong M. Rho, Ray W. Turner, Ning Cheng
Summary: The selective inhibitor PD325901 was found to successfully reduce core pathological deficits in the BTBR mouse model of autism, including impaired sociability, vocalization, and repetitive behavior, and restored abnormal EEG signals. These results further support the critical involvement of the ERK pathway in the pathophysiology of autism and suggest that a similar approach could be applied to other animal models with dysregulated ERK signaling.
Article
Immunology
Abi G. Yates, Elena Kislitsyna, Carla Alfonso Martin, Jiaying Zhang, Amy L. Sewell, Ane Goikolea-Vives, Valerie Cai, Lama F. Alkhader, Aleksander Skaland, Basil Hammond, Ralica Dimitrova, Dafnis Batalle, Cathy Fernandes, A. David Edwards, Pierre Gressens, Claire Thornton, Helen B. Stolp
Summary: In this study, the efficacy of montelukast in a mouse model of encephalopathy of prematurity (EoP) was evaluated. The results showed that montelukast can attenuate inflammation, improve grey matter neuropathology, and ameliorate behavior deficits, suggesting that early administration of repurposed montelukast may improve the development and outcome of EoP.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Wei Shao, Hang Zheng, Jingwen Zhu, Wenhao Li, Yifan Li, Wenjie Hu, Juanjuan Zhang, Liang Jing, Kai Wang, Xiao Jiang
Summary: Autism spectrum disorder (ASD) is a highly inherited neurodevelopmental disorder, and loss-of-function mutations in the CACNA2D3 gene are associated with ASD. Dysfunction of cortical interneurons (INs), specifically Parvalbumin-expressing (PV) INs, may underlie the abnormal social behavior observed in ASD. Knockout mouse models were used to investigate the role of Cacna2d3 insufficiency in PV neurons, and it was found that these mice exhibited deficits in core ASD behaviors, anxiety-like behavior, and improved spatial memory. On the other hand, mice with Cacna2d3 insufficiency in somatostatin-expressing (SOM) neurons did not show obvious deficits in social, cognitive, or emotional phenotypes.
NEUROCHEMISTRY INTERNATIONAL
(2023)
Article
Clinical Neurology
Zhongpeng Dai, Hongliang Zhou, Wei Zhang, Hao Tang, Ting Wang, Zhilu Chen, Zhijian Yao, Qing Lu
Summary: The study revealed abnormal neural oscillations in patients with suicidal attempts during inhibitory control tasks, characterized by power changes in different brain regions and alpha-beta decoupling from VPFC to dACC significantly correlated with suicide risk level.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Neurosciences
Viktor Roman, Nika Adham, Andrew G. Foley, Lynsey Hanratty, Bence Farkas, Balazs Lendvai, Bela Kiss
Summary: This study aimed to investigate the effects of Cariprazine in a rat ASD model compared to Risperidone and Aripiprazole. The results showed that Cariprazine demonstrated dose-dependent efficacy on behavioral endpoints and may be useful in the treatment of ASD symptoms.
PSYCHOPHARMACOLOGY
(2021)
Article
Behavioral Sciences
Ruiqi Pang, Sumei Yan, Yunfeng Tu, Shaowen Qian, Haipeng Yu, Xianli Hu, Huizhong Wen, Wei Yuan, Xing Wang, Yi Zhou
Summary: Hearing abnormalities are important symptoms of autism spectrum disorders (ASDs). This study found that transient hearing abnormalities can be observed in Shank3B knockout mice, and these abnormalities are most prominent before the onset of social deficits. Additionally, support vector machine analysis can accurately predict the genotype of mice based on auditory brainstem response data.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Psychiatry
Maximiliano Rapanelli, Wei Wang, Edward Hurley, Maria Laura Feltri, Christopher Pittenger, Luciana Romina Frick, Zhen Yan
Summary: Loss-of-function mutations of the gene Cul3 are risk factors for autism-spectrum disorder (ASD), and studying mice with ablation of Cul3 in cholinergic neurons has helped understand the pathogenic mechanisms. Cholinergic dysfunction due to Cul3 deficiency is involved in ASD-like behavioral abnormalities, and basal forebrain (BF) cholinergic neurons play a critical role in cognition through their projections to the prefrontal cortex (PFC).
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Neurosciences
Saroj Sah, Ryan Keable, Grant Pfundstein, Kelly J. Clemens, Denovan Begg, Melitta Schachner, Iryna Leshchyns'ka, Vladimir Sytnyk
Summary: The presence of NCAM2 in the central nervous system is crucial for regulating axonal organization. NCAM2 stimulates the levels of BACE1, a protease involved in axonal guidance. Loss of NCAM2 leads to decreased BACE1 levels and abnormal axonal organization, resulting in impaired spatial memory and cognitive flexibility. In addition, NCAM2 deficiency also affects behavior in mice, with increased self-grooming and altered sensory responses.
Article
Genetics & Heredity
Markus Wohr, Wendy M. Fong, Justyna A. Janas, Moritz Mall, Christian Thome, Madhuri Vangipuram, Lingjun Meng, Thomas C. Sudhof, Marius Wernig
Summary: Myt1l is a neuron-specific transcription factor that plays an important role in maintaining neuronal identity. Mutations in MYT1L have been associated with intellectual disability and autism spectrum disorder. In this study, researchers generated and characterized Myt1l-deficient mice and found that these mice exhibited behavioral alterations similar to those observed in humans with MYT1L mutations, making them a valuable model for studying the MYT1L syndrome.
Article
Neurosciences
Arushi Sandhu, Kajal Rawat, Vipasha Gautam, Antika Sharma, Anil Kumar, Lekha Saha
Summary: This study investigated the pharmacological effects of ibudilast in a prenatal valproic acid (VPA) model of autism spectrum disorder (ASD) in Wistar rats. The results showed that ibudilast significantly improved social interaction, spatial learning, anxiety, hyperactivity, and decreased nociceptive threshold, as well as reduced oxidative stress, inflammation, glial cell activation, and neuronal damage in the brain. In conclusion, ibudilast treatment restored crucial ASD-related behavioral abnormalities, potentially through neuroprotection.
Article
Biochemistry & Molecular Biology
Mohammed M. Alanazi, Mushtaq A. Ansari, Ahmed Nadeem, Sabry M. Attia, Saleh A. Bakheet, Haneen A. Al-Mazroua, Abdullah A. Aldossari, Mohammed M. Almutairi, Thamer H. Albekairi, Marwa H. Hussein, Mohammed A. Al-Hamamah, Sheikh F. Ahmad
Summary: This study found that cadmium exposure exacerbates self-grooming and marble-burying behaviors, decreases social interactions, and leads to immune abnormalities in an autism spectrum disorder animal model. Further investigation revealed potential molecular mechanisms underlying these effects. These findings have important implications for the etiology of autism spectrum disorders and provide further evidence of heavy metals contributing to neurodevelopmental disorders through proinflammatory effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Matthew R. Bruce, Karen L. Jones, Anthony C. Vernon, Jill L. Silverman, Jacqueline N. Crawley, Jacob Ellegood, Jason P. Lerch, Judy Van de Water
Summary: The study suggests that maternal autoantibodies may play a significant role in immune responses leading to autism spectrum disorder, causing changes in offspring neurodevelopment and behavior. Findings indicate that offspring prenatally exposed to MAR-ASD autoantibodies exhibit increased brain volume, altered regional relationships, and gender-specific effects on social interaction and repetitive self-grooming behavior in adulthood.
MOLECULAR PSYCHIATRY
(2021)
Article
Behavioral Sciences
Yuen Gao, Mohammad B. Aljazi, Jin He
Summary: This study reveals a potential causal link between disruptive KDM6B mutations and ASD/ADHD-like behavioral deficits using an animal model. It also provides a new mouse model for studying the cellular and molecular mechanisms underlying Kdm6b-mutation-related neurodevelopmental disorders.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Cell Biology
Seongbin Kim, Hyoseon Oh, Sang Han Choi, Ye-Eun Yoo, Young Woo Noh, Yisul Cho, Geun Ho Im, Chanhee Lee, Yusang Oh, Esther Yang, Gyuri Kim, Won-Suk Chung, Hyun Kim, Hyojin Kang, Yongchul Bae, Seong-Gi Kim, Eunjoon Kim
Summary: In this study, researchers found that Myt1l deficiency in mice leads to autism-related phenotypes, which exhibit age-dependent characteristics. The study also suggests that while the reduction of Myt1l expression in juveniles temporarily improves these phenotypes, they reappear in adults.
Article
Developmental Biology
Theresa M. Kisko, Rainer K. W. Schwarting, Markus Woehr
Summary: Sexual dimorphisms are evident in the emission of 50-kHz ultrasonic vocalizations during rough-and-tumble play in juvenile rats, with females showing reduced emission rates compared to males. These sex differences are modulated by the Cacna1c gene and result in a masculinized social play repertoire in female rats with Cacna1c haploinsufficiency.
DEVELOPMENTAL PSYCHOBIOLOGY
(2021)
Article
Clinical Neurology
Maria Willadsen, Metin Uengoer, Rainer K. W. Schwarting, Judith R. Homberg, Markus Woehr
Summary: The study found that SERT deficiency has an impact on fear-related behavior and alarm 22-kHz USV in rats, particularly more prominent in females. Rats lacking SERT may have social deficits that hinder them from effectively using 22-kHz USV as a socio-affective signal to warn conspecifics.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Review
Pharmacology & Pharmacy
Markus Woehr
Summary: Rats emit 50-kHz ultrasonic vocalizations in appetitive situations, particularly elicited by d-amphetamine, and can serve as a reliable measure for assessing elevated mood in rats. Pharmacological interventions can modulate this vocalization, providing new insights into manic behaviors and potential therapeutic targets.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Behavioral Sciences
Logan J. Bigelow, Catherine Fiset, Jack H. M. Jarvis, Sarah Macleod, Markus Wohr, Tim A. Benke, Paul B. Bernard
Summary: Early-life seizures are associated with autism spectrum disorder, and deficits in auditory communication were observed in adult male rats following a single episode of kainic acid-induced early-life seizures, potentially contributing to previously reported social deficits associated with ELS.
EPILEPSY & BEHAVIOR
(2022)
Review
Behavioral Sciences
Jill L. Silverman, Audrey Thurm, Sarah B. Ethridge, Makayla M. Soller, Stela P. Petkova, Ted Abel, Melissa D. Bauman, Edward S. Brodkin, Hala Harony-Nicolas, Markus Woehr, Alycia Halladay
Summary: Neurodevelopmental disorders (NDDs) are prevalent and lifelong disorders without evidence-based interventions. Optimal utilization of preclinical animal models is crucial. A workshop in the field of behavioral neuroscience reviewed current studies and proposed solutions, including re-evaluating animal model links to NDDs.
GENES BRAIN AND BEHAVIOR
(2022)
Article
Biochemistry & Molecular Biology
Thomas Henzi, Kim-Long Diep, Anne Oberson, Valerie Salicio, Christian G. Bochet, Beat Schwaller
Summary: Malignant mesothelioma (MM) is an aggressive cancer derived from mesothelial cells, often caused by asbestos exposure. The current treatment options are limited in effectiveness, hence the search for novel therapies. Recent research has identified septins as a potential target for treatment. Some FCF analogs have been found to inhibit the growth of MM cells in vitro, but at concentrations too high for clinical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Reda Juskeviciene, Ann-Kristina Fritz, Margarita Brilkova, Rashid Akbergenov, Karen Schmitt, Hubert Rehrauer, Endre Laczko, Patricia Isnard-Petit, Kader Thiam, Anne Eckert, Jochen Schacht, David P. Wolfer, Erik C. Boettger, Dimitri Shcherbakov
Summary: A point mutation V336Y in mitoribosomal protein Mrps5 (uS5m) has been recently identified as a ribosomal ambiguity (ram) mutation causing error-prone mitochondrial protein synthesis. In transgenic knock-in animals, a homologous mutation V338Y is associated with a specific phenotype including impaired mitochondrial function, behavioral alterations, hearing damage, and accelerated metabolic aging in muscle. However, a homologous G -> R mutation in mitoribosomal Mrps5 did not affect the accuracy of mitochondrial protein synthesis, suggesting a challenge to the postulated link between Mrps5 V338Y-mediated misreading and the in vivo phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Psychology, Biological
Nivethini Sangarapillai, Markus Woehr, Rainer K. W. Schwarting
Summary: This study investigated sign and goal-tracking behavior and the emission of 50 kHz ultrasonic vocalizations (USV) in Cacna1c haploinsufficent rats. The results showed that these rats increased their approach to the reward site and their rates of pressing the inoperable lever. They also displayed reduced numbers of appetitive 50 kHz calls compared to wildtype controls. These findings provide evidence for 50 kHz calls as a trait marker and suggest altered dopamine signaling in Cacna1c haploinsufficent rats.
PHYSIOLOGY & BEHAVIOR
(2022)
Article
Multidisciplinary Sciences
Valeria Petroni, Enejda Subashi, Marika Premoli, Markus Woehr, Wim E. Crusio, Valerie Lemaire, Susanna Pietropaolo
Summary: Fragile X Syndrome (FXS), caused by a genetic mutation, is a common heritable form of mental retardation and autism spectrum disorder (ASD). Environmental adversity may interact with the genetic mutation to exacerbate and influence the symptoms. Our study found that prenatal exposure to chronic stress affected the behavioral phenotype of Fmr1 knockout (KO) mice, particularly in males, highlighting the sex-dependent relevance of early environmental stressors interacting with genetic factors.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Markus Wohr, Wendy M. Fong, Justyna A. Janas, Moritz Mall, Christian Thome, Madhuri Vangipuram, Lingjun Meng, Thomas C. Sudhof, Marius Wernig
Summary: Myt1l is a neuron-specific transcription factor that plays an important role in maintaining neuronal identity. Mutations in MYT1L have been associated with intellectual disability and autism spectrum disorder. In this study, researchers generated and characterized Myt1l-deficient mice and found that these mice exhibited behavioral alterations similar to those observed in humans with MYT1L mutations, making them a valuable model for studying the MYT1L syndrome.
Article
Biochemistry & Molecular Biology
Helena C. Martins, Carlotta Gilardi, A. Oezge Sungur, Jochen Winterer, Michael A. Pelzl, Silvia Bicker, Fridolin Gross, Theresa M. Kisko, Natalia Malikowska-Racia, Moria D. Braun, Katharina Brosch, Igor Nenadic, Frederike Stein, Susanne Meinert, Rainer K. W. Schwarting, Udo Dannlowski, Tilo Kircher, Markus Woehr, Gerhard Schratt
Summary: This study reveals that miR-499-5p regulates dendritogenesis and cognitive function by downregulating the BD risk gene CACNB2. The expression of miR-499-5p is increased in the peripheral blood of BD patients and in the hippocampus of rats exposed to social isolation. In rat hippocampal neurons, miR-499-5p impairs dendritogenesis and reduces the surface expression and activity of Cav1.2 calcium channel. CACNB2, which encodes a beta-subunit of Cav1.2, was identified as a direct target of miR-499-5p in neurons.
Article
Neurosciences
Annuska Berz, Camila Pasquini de Souza, Markus Woehr, Sebastian Steinmueller, Maria Bruntsch, Martin K-H Schaefer, Rainer K. W. Schwarting
Summary: This study investigated the habituation of rats to repeated exposure to 50kHz ultrasonic vocalizations (USV) and its relationship with the presence of contingent social consequences. The results showed that the habituation to the USV was not affected by the presence or absence of social consequences. Furthermore, no substantial activation of the nucleus accumbens was observed during the retest, while unexpected strong activation was detected in the anterior cingulate cortex, indicating its involvement in the response to the USV in individual rats.
Article
Biochemistry & Molecular Biology
Hauke Fender, Kim Walter, Aytug K. Kiper, Jelena Plackic, Theresa M. Kisko, Moria D. Braun, Rainer K. W. Schwarting, Susanne Rohrbach, Markus Woehr, Niels Decher, Jens Kockskaemper
Summary: CACNA1C gene is associated with neuropsychiatric and cardiac disease, and Cacna1c(+/-) rats are a newly developed model with a behavioral phenotype. This study reveals that Cacna1c(+/-) rats exhibit altered Ca2+ handling mechanisms in cardiac myocytes under basal conditions, and this alteration is further enhanced by the effect of isoprenaline.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Psychology, Biological
Emilie Bartsoen, Markus Woehr
Summary: Adult male rats emit ultrasonic vocalizations (USV) at 22-kHz and 50-kHz frequencies during the acoustic startle response test. The 22-kHz calls indicate a negative affective state, while the 50-kHz calls indicate a positive affective state.
PHYSIOLOGY & BEHAVIOR
(2023)
Article
Genetics & Heredity
Jan Gehlen, Ann-Sophie Giel, Ricarda Koellges, Stephan L. Haas, Rong Zhang, Jiri Trcka, Ayse O. Sungur, Florian Renziehausen, Dorothea Bornholdt, Daphne Jung, Paul D. Hoyer, Agneta Nordenskjold, Dick Tibboel, John Vlot, Manon C. W. Spaander, Robert Smigiel, Dariusz Patkowski, Nel Roeleveld, Iris Alm van Rooij, Ivo de Blaauw, Alice Hoelscher, Marcus Pauly, Andreas Leutner, Joerg Fuchs, Joel Niethammer, Maria-Theodora Melissari, Ekkehart Jenetzky, Nadine Zwink, Holger Thiele, Alina Christine Hilger, Timo Hess, Jessica Trautmann, Matthias Marks, Martin Baumgarten, Gaby Blaess, Mikael Landen, Bengt Fundin, Cynthia M. Bulik, Tracie Pennimpede, Michael Ludwig, Kerstin U. Ludwig, Elisabeth Mangold, Stefanie Heilmann-Heimbach, Susanne Moebus, Bernhard G. Herrmann, Kristina Alsabeah, Carmen M. Burgos, Helene E. Lilja, Sahar Azodi, Pernilla Stenstrom, Einar Arnbjornsson, Barbora Frybova, Dariusz M. Lebensztejn, Wojciech Debek, Elwira Kolodziejczyk, Katarzyna Kozera, Jaroslaw Kierkus, Piotr Kalicinski, Marek Stefanowicz, Anna Socha-Banasiak, Michal Kolejwa, Anna Piaseczna-Piotrowska, Elzbieta Czkwianianc, Markus M. Noethen, Phillip Grote, Michal Rygl, Konrad Reinshagen, Nicole Spychalski, Barbara Ludwikowski, Jochen Hubertus, Andreas Heydweiller, Benno Ure, Oliver J. Muensterer, Ophelia Aubert, Jan-Hendrik Gosemann, Martin Lacher, Petra Degenhardt, Thomas M. Boemers, Anna Mokrowiecka, Ewa Malecka-Panas, Markus Woehr, Michael Knapp, Guido Seitz, Annelies de Klein, Grzegorz Oracz, Erwin Brosens, Heiko Reutter, Johannes Schumacher
Summary: This study identifies three risk loci and candidate genes associated with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) through a genome-wide association study (GWAS), providing insights into the genetic architecture of EA/TEF.
HUMAN GENETICS AND GENOMICS ADVANCES
(2022)