Article
Biochemistry & Molecular Biology
Alice Zambon, Laura Cuenca Rico, Mathieu Herman, Anna Gundacker, Amina Telalovic, Lisa-Marie Hartenberger, Rebekka Kuehn, Roman A. Romanov, S. Abid Hussaini, Tibor Harkany, Daniela D. Pollak
Summary: Immune activation during pregnancy has detrimental effects on parenting behavior in mouse dams, potentially due to changes in hypothalamic neurocircuit parameters and altered gene activation in specific neurons.
MOLECULAR PSYCHIATRY
(2022)
Review
Endocrinology & Metabolism
Lisa Koshko, Sydney Scofield, Gil Mor, Marianna Sadagurski
Summary: Environmental contaminants in ambient air pollution pose a serious risk to long-term metabolic health, with prenatal exposure increasing the risk of Type II Diabetes in children. The hypothalamus, located in the central nervous system, plays a critical role in regulating metabolism and may be susceptible to developmental alterations affecting metabolic programming.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Miriam Ryl, Alexander Urbasik, Kaspar Gierke, Norbert Babai, Anneka Joachimsthaler, Andreas Feigenspan, Renato Frischknecht, Nina Stallwitz, Anna Fejtova, Jan Kremers, Julia von Wittgenstein, Johann Helmut Brandstaetter
Summary: The study investigated the impact of mutations in the Bassoon protein on the synaptic function and structure of photoreceptor cells in mice. Results showed that the synaptic defects were more severe in Bsn(gt/gt) mice, while expression of the Bsn(gt) allele led to cone photoreceptor death and neurite sprouting in the outer retina.
Article
Endocrinology & Metabolism
Elna Dickson, Rana Soylu-Kucharz, Asa Petersen, Maria Bjorkqvist
Summary: This study aimed to investigate the effects of hypothalamic huntingtin (HTT) protein levels on metabolic phenotype and disease features in Huntington's disease (HD). The results showed that hypothalamic overexpression of mutant HTT led to weight gain, particularly in the early stages of the disease, accompanied by behavioral alterations and transcriptional changes.
MOLECULAR METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Shulan Qiu, Sijia He, Jianing Wang, Hu Wang, Anindita Bhattacharjee, Xin Li, Moawiz Saeed, Jeffrey L. Dupree, Xianlin Han
Summary: The interaction between obesity and central nervous system (CNS) neurological dysfunction is well recognized. Evidence shows that obesity is a risk factor for CNS neuroinflammation and cognitive impairment. This study investigates how CNS sulfatide deficiency affects peripheral metabolism, considering sex- and age-specific effects. Results show that female sulfatide-deficient mice gained more body weight, had higher basal glucose levels, and were glucose intolerant compared to controls, while male sulfatide-deficient mice only showed glucose intolerance at a later age compared to females. Increased body weight was associated with increased food intake and elevated neuroinflammation in a sex-specific manner, suggesting that CNS sulfatide deficiency leads to sex-specific alterations in energy homeostasis via dysregulated hypothalamic control of food intake.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Sandra Franco-Iborra, Ainhoa Plaza-Zabala, Marta Montpeyo, David Sebastian, Miquel Vila, Marta Martinez-Vicente
Summary: The study found that HTT protein plays a crucial role in mitophagy, and the expansion of its polyQ tract affects this process, ultimately leading to the accumulation of damaged mitochondria and an increase in oxidative stress, leading to negative effects on mitochondrial dysfunction and neurodegeneration in Huntington disease.
Article
Biochemistry & Molecular Biology
Laura L. Koekkoek, Margo Slomp, Julien Castel, Michael Mutersbaugh, Ian Linville, Mireille J. Serlie, Serge H. Luquet, Susanne E. la Fleur
Summary: Research shows that glutamatergic neurons in the lateral hypothalamus can differentiate between low-calorie sweeteners and caloric sweeteners, and consuming a high fat diet disrupts their ability to detect calories.
Article
Cell Biology
Nicole M. Sayles, Nneka Southwell, Kevin McAvoy, Kihwan Kim, Alba Pesini, Corey J. Anderson, Catarina Quinzii, Suzanne Cloonan, Hibiki Kawamata, Giovanni Manfredi
Summary: Mitochondrial cardiomyopathies are fatal diseases with no effective treatment. This study reveals cardiac metabolic rewiring triggered by CHCHD10 gene mutation and the associated mechanisms of metabolic imbalance.
Article
Environmental Sciences
Quan Zhang, Sijia Gu, Yan Wang, Shitao Hu, Siqing Yue, Cui Wang
Summary: This study revealed that the alpha isomer of Cypermethrin (CYP) caused significant weight loss and hepatic glycogen accumulation in rats. It also found a correlation between changes in gut microbiome and CYP toxicity.
JOURNAL OF ENVIRONMENTAL SCIENCES
(2023)
Article
Environmental Sciences
Quan Zhang, Sijia Gu, Yan Wang, Shitao Hu, Siqing Yue, Cui Wang
Summary: The study reveals that alpha-CYP causes weight loss, hepatic glycogen accumulation, and hyperlipemia in rats, while theta-CYP induces systemic inflammation. The gut microbiome composition differs significantly in the alpha-CYP-treated group, with lower levels of Firmicutes and higher levels of Verrucomicrobia. Short-chain fatty acids (SCFAs) are associated with blood glucose and Verrucomicrobia, which may explain the differential effects of alpha-CYP and theta-CYP.
JOURNAL OF ENVIRONMENTAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xuyuan Kuang, Kyle Nunn, Jennifer Jiang, Paul Castellano, Uttara Hardikar, Arianna Horgan, Joyce Kong, Zhiqun Tan, Wei Dai
Summary: Studies have shown that mHTT can spread between cells, leading to the propagation of misfolded protein pathology. By using correlative light and electron microscopy and cryo-electron tomography, researchers identified the structure of transmissive mHTT species and highlighted the potential role of extracellular vesicles (EVs) in the transmission process.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Neurosciences
Stefan Passlick, Christine R. Rose, Gabor C. Petzold, Christian Henneberger
Summary: High-affinity, Na+-dependent glutamate transporters play a crucial role in removing synaptically released glutamate, thus increasing spatial precision of synaptic communication. Dysfunction of these transporters can lead to elevated glutamate concentration, enhanced spread, and potentially neuronal death.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Kuniyuki Aso, Michihito Kono, Masatoshi Kanda, Yuki Kudo, Kodai Sakiyama, Ryo Hisada, Kohei Karino, Yusho Ueda, Daigo Nakazawa, Yuichiro Fujieda, Masaru Kato, Olga Amengual, Tatsuya Atsumi
Summary: The study reveals that itaconate can alter T cell function and impact the development of autoimmune diseases through modulation of metabolic and epigenetic programs. Itaconate inhibits Th17 cell differentiation and promotes Treg cell differentiation by suppressing glycolysis and oxidative phosphorylation. The metabolic changes induced by itaconate also affect chromatin accessibility, transcription factor binding, and gene expression in Th17 and Treg cell differentiation. Furthermore, the adoptive transfer of itaconate-treated Th17 cells can ameliorate autoimmune encephalomyelitis. These findings suggest that itaconate is a crucial metabolic regulator for Th17/Treg cell balance and can be a potential therapeutic agent for autoimmune diseases.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Elna Dickson, Amoolya Sai Dwijesha, Natalie Andersson, Sofia Lundh, Maria Bjorkqvist, Asa Petersen, Rana Soylu-Kucharz
Summary: This study investigated the transcriptional changes caused by hypothalamic expression of huntingtin (HTT) gene in Huntington's disease (HD). The results showed that both wild-type HTT (wtHTT) and mutant HTT (mHTT) overexpression altered the hypothalamic transcriptome profile, with mHTT specifically affecting neuroendocrine circuits. However, the ubiquitous expression of full-length mHTT in the BACHD mouse model moderately affected the transcriptomic profile.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Nikhil Maheshwari, Aijaz Ahmed Khan, Riaz Mahmood
Summary: Pentachlorophenol (PCP), widely used in biocide and pesticide industries, causes oxidative damage to rat kidneys by increasing reactive oxygen species (ROS) and inhibiting antioxidant enzymes. PCP treatment also results in DNA damage, dysfunction of brush border membrane (BBM) enzymes, and increased plasma levels of creatinine and urea. These findings highlight the significance of PCP-induced oxidative stress in nephrotoxicity.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Osama Elabi, Abderahim Gaceb, Robert Carlsson, Thomas Padel, Rana Soylu-Kucharz, Irene Cortijo, Wen Li, Jia-Yi Li, Gesine Paul
Summary: The pathological hallmark of Parkinson's disease is the formation of Lewy bodies containing alpha-synuclein, but microvascular alterations have also been linked to neurodegeneration in PD. Using a human alpha-synuclein overexpression mouse model, researchers demonstrated compromised blood-brain barrier integrity, dynamic changes in vessel morphology, and activation of pericytes, supporting the occurrence of vascular pathology as an important aspect in PD. This model provides a powerful tool to investigate disease-modifying factors and guide the development of new treatments for Parkinson's disease.
SCIENTIFIC REPORTS
(2021)
Article
Clinical Neurology
Alexander Svanbergsson, Fredrik Ek, Isak Martinsson, Jordi Rodo, Di Liu, Edoardo Brandi, Caroline Haikal, Laura Torres-Garcia, Wen Li, Gunnar Gouras, Roger Olsson, Tomas Bjorklund, Jia-Yi Li
Summary: This study identified inhibitors capable of preventing α-synuclein aggregation by targeting p38 MAPK and PKC, suggesting their potential therapeutic value. The research also revealed alterations in the endo-lysosomal system as likely candidates for the protective effects, underscoring the importance of high-throughput screening in investigating α-synuclein aggregation mechanisms and discovering novel therapeutic compounds.
Review
Neurosciences
Tomas Bjorklund, Marcus Davidsson
Summary: Recent technological and conceptual advances have led to a variety of novel engineered AAV vector variants, including synthetic capsids with potential in treating PD and future therapeutic strategies.
JOURNAL OF PARKINSONS DISEASE
(2021)
Article
Multidisciplinary Sciences
Jo B. Henningsen, Rana Soylu-Kucharz, Maria Bjorkqvist, Asa Petersen
Summary: Huntington disease is a fatal neurodegenerative movement disorder caused by a mutant huntingtin protein. Despite certain brain regions being affected, the role of excitotoxicity in the loss of hypothalamic neuronal populations in HD remains unclear. Further research is needed to understand the underlying mechanisms of selective vulnerability of certain neurons in HD.
Article
Cell & Tissue Engineering
Patrick Aldrin-Kirk, Malin Akerblom, Tiago Cardoso, Sara Nolbrant, Andrew F. Adler, Xiaohe Liu, Andreas Heuer, Marcus Davidsson, Malin Parmar, Tomas Bjorklund
Summary: Transplanting hESC-derived DA neurons in Parkinson's disease using a novel virus vector to observe their projections, revealing potential integration with host circuitry based on differential afferent inputs.
Article
Multidisciplinary Sciences
Rana Soylu-Kucharz, Ali Khoshnan, Asa Petersen
Summary: Huntington disease is a neurodegenerative disorder caused by a genetic mutation, leading to metabolic imbalance, especially in the hypothalamus. Female mice show an obese phenotype when expressing mutant HTT in the hypothalamus, while inactivation of the IKK beta gene can inhibit weight gain.
Article
Endocrinology & Metabolism
Elna Dickson, Rana Soylu-Kucharz, Asa Petersen, Maria Bjorkqvist
Summary: This study aimed to investigate the effects of hypothalamic huntingtin (HTT) protein levels on metabolic phenotype and disease features in Huntington's disease (HD). The results showed that hypothalamic overexpression of mutant HTT led to weight gain, particularly in the early stages of the disease, accompanied by behavioral alterations and transcriptional changes.
MOLECULAR METABOLISM
(2022)
Article
Neurosciences
Elna Dickson, Amoolya Sai Dwijesha, Natalie Andersson, Sofia Lundh, Maria Bjorkqvist, Asa Petersen, Rana Soylu-Kucharz
Summary: This study investigated the transcriptional changes caused by hypothalamic expression of huntingtin (HTT) gene in Huntington's disease (HD). The results showed that both wild-type HTT (wtHTT) and mutant HTT (mHTT) overexpression altered the hypothalamic transcriptome profile, with mHTT specifically affecting neuroendocrine circuits. However, the ubiquitous expression of full-length mHTT in the BACHD mouse model moderately affected the transcriptomic profile.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cell Biology
Kerstin Griess, Michael Rieck, Nadine Muller, Gergely Karsai, Sonja Hartwig, Angela Pelligra, Robert Hardt, Caroline Schlegel, Jennifer Kuboth, Celina Uhlemeyer, Sandra Trenkamp, Kay Jeruschke, Jurgen Weiss, Leon Peifer-Weiss, Weiwei Xu, Sandra Cames, Xiaoyan Yi, Miriam Cnop, Mathias Beller, Holger Stark, Arun Kumar Kondadi, Andreas S. Reichert, Daniel Markgraf, Marianne Wammers, Dieter Haeussinger, Oliver Kuss, Stefan Lehr, Decio Eizirik, Heiko Lickert, Eckhard Lammert, Michael Roden, Dominic Winter, Hadi Al-Hasani, Doris Hoeglinger, Thorsten Hornemann, Jens C. Bruning, Bengt-Frederik Belgardt
Summary: Impaired proinsulin-to-insulin processing in pancreatic beta-cells is a key defective step in both type 1 diabetes and type 2 diabetes. This study reveals the roles of specific sphingolipid species and sphingolipid-binding proteins in beta-cell function and T2D-associated beta-cell failure.
NATURE CELL BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Celina Uhlemeyer, Nadine Mueller, Michael Rieck, Jennifer Kuboth, Caroline Schlegel, Kerstin Griess, Tim Florian Dorweiler, Sonja Heiduschka, Juergen Eckel, Michael Roden, Eckhard Lammert, Markus Stoffel, Bengt -Frederik Belgardt
Summary: In this study, the role of P53 in beta cells was investigated using beta cell specific knockout mice. The results showed that P53 is not essential for beta cell failure and death, suggesting that P53 signaling in other cell types and organs may predominantly regulate glucose homeostasis.
MOLECULAR METABOLISM
(2023)
Article
Geriatrics & Gerontology
Oleg Zhukov, Chen He, Rana Soylu-Kucharz, Changsi Cai, Andreas D. Lauritzen, Blanca Irene Aldana, Maria Bjorkqvist, Martin Lauritzen, Krzysztof Kucharz
Summary: Using two-photon microscopy and microscopy, this study observed the function of cerebral vasculature and neurovascular coupling in an AD mouse model. The results showed that the blood-brain barrier and neurovascular coupling were preserved, and the density of capillary pericytes was not affected. These findings suggest that microvascular function is preserved in the 5xFAD mice and highlight the importance of choosing appropriate preclinical models of AD.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Cansu Ozdemir, Duygu Akcay, Digdem Yoyen-Ermis, Ekim Zihni Taskiran, Rana Soylu-Kucharz, Guenes Esendagli, Yusuf Cetin Kocaefe
Summary: Chronic skeletal muscle degeneration is characterized by fiber atrophy accompanied by deposition of extracellular matrix (ECM) components and fatty infiltration. Excessive accumulation of ECM leads to fibrosis via the contribution of fibro-adipogenic precursors (FAPs). Fibrosis also accompanies disuse atrophy and sarcopenia without significant inflammation.
Article
Neurosciences
Elna Dickson, Claes Fryklund, Rana Soylu-Kucharz, Marie Sjogrena, Karin G. Stenkula, Maria Bjorkqvista
Summary: The present study investigates the molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice. The study found early sex-specific changes in adipocyte cell size distribution in WAT of R6/2 and leptin-deficient R6/2 mice. Female mice had a reduction in body weight accompanied by an increased proportion of smaller adipocytes, while male mice displayed a shift towards larger adipocyte sizes without significant body weight reduction.
JOURNAL OF HUNTINGTONS DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Delsi Altenhofen, Jenny Minh-An Khuong, Tanja Kuhn, Sandra Lebek, Sarah Goerigk, Katharina Kaiser, Christian Binsch, Kerstin Griess, Birgit Knebel, Bengt-Frederik Belgardt, Sandra Cames, Samaneh Eickelschulte, Torben Stermann, Axel Rasche, Ralf Herwig, Juergen Weiss, Heike Vogel, Annette Schuermann, Alexandra Chadt, Hadi Al-Hasani
Summary: By using a combined approach, including positional cloning, gene expression analyses, and in silico predictions, we identified the novel T2D-associated gene Nbg15 and its potential causative genes Cbx6, Fam135b, and Kdelr3, which are involved in the dysfunction of pancreatic beta cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Mathematical & Computational Biology
Lina Marcela Gallego-Paez, Jan Mauer
Summary: RNA-seq analysis has greatly enhanced our understanding of transcriptome complexity in health and disease. However, the use of existing bioinformatic pipelines for transcriptome-wide splicing analysis is limited to experts in the field. This article introduces DJExpress, an R package that allows differential expression analysis of transcriptomic features and their associations with molecular/clinical traits. DJExpress can handle both annotated and de novo identified splice junctions and provides interactive and intuitive visualization formats. It also offers a web-compatible graphical interface for data analysis and visualization of splice events. DJExpress is a powerful and user-friendly tool for exploring alternative splicing alterations in RNA-seq data.
FRONTIERS IN BIOINFORMATICS
(2022)