Review
Biochemistry & Molecular Biology
Sebastien G. Bouret
Summary: The melanocortin system in the brain regulates feeding behavior, energy balance, and body weight. Investigating its development is helping researchers understand and explore treatments for chronic diseases, including obesity and type-2 diabetes. Disruption of the melanocortin system's development may lead to metabolic consequences later in life.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Review
Cell Biology
Yinqiong Huang, Xiahong Lin, Shu Lin
Summary: This research over the past decade has suggested that the pathogenic mechanisms of metabolic syndrome involve both peripheral tissues and central metabolic regulation imbalances. The hypothalamus, particularly the arcuate nucleus, is highlighted as the control center for metabolic homeostasis and energy balance, with Neuropeptide Y neurons playing a crucial role in integrating peripheral metabolic signals with the brain center. The manuscript aims to provide an overview of Neuropeptide Y's regulatory effects on metabolic syndrome and discuss clinical intervention strategies for neurometabolic diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Chen-Liang Zhang, Yi-Zhang Lin, Qi Wu, Chenxu Yan, Matthew Wai-Kin Wong, Fan Zeng, Ping Zhu, Kelsey Bowes, Kailun Lee, Xuan Zhang, Zhi-Yuan Song, Shu Lin, Yan-Chuan Shi
Summary: Chronic high salt intake is a leading cause of hypertension. This study demonstrates that high salt intake results in downregulation of NPY expression in the hypothalamic Arc and upregulation of BDNF and vasopressin expression in the PVN, leading to the development of hypertension.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Anatomy & Morphology
Yvette Ruska, Anett Szilvasy-Szabo, Dora Kovari, Andrea Kadar, Lilla Macsai, Richard Sinko, Erik Hrabovszky, Balazs Gereben, Csaba Fekete
Summary: The study shows the presence of GLP-1 receptor (GLP-1R) protein and mRNA in orexigenic neuropeptide Y (NPY) neurons in the ventromedial arcuate nucleus, along with the innervation of NPY neurons by inhibitory neurons containing GLP-1R. This suggests that GLP-1 signaling can influence NPY neurons both directly and indirectly, revealing a more complex mechanism of GLP-1's effects on energy homeostasis.
BRAIN STRUCTURE & FUNCTION
(2022)
Article
Neurosciences
Jae Hyun Cho, Kyungchan Kim, Han Chae Cho, Jaemeun Lee, Eun-Kyoung Kim
Summary: The study demonstrates the central role of FGF11 in metabolism regulation. Knockdown of FGF11 leads to reduced weight gain and fat mass, increased thermogenesis in brown adipose tissue, and improved glucose and insulin tolerances under high-fat diet conditions. FGF11 regulates Npy gene expression through the glycogen synthase kinase 3-cAMP response element-binding protein pathway.
Article
Biology
Mitsuhiro Yoshimura, Benjamin P. Flynn, Yvonne M. Kershaw, Zidong Zhao, Yoichi Ueta, Stafford L. Lightman, Becky L. Conway-Campbell
Summary: This study demonstrates how the timing of feeding behavior becomes disordered when glucocorticoid rhythms are dissociated from lighting cues. The dysregulated timing of neuropeptide gene expression is associated with this altered feeding pattern.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yanni Zhang, Qiulei Xi, Ming Zhong, Yi Jiang, Qiulin Zhuang, Zuoyou Ding, Shanjun Tan, Junjie Wang, Hao Liu, Zhige Zhang, Ben Zhou, Guohao Wu
Summary: Cachexia is common in cancer patients and its molecular basis is still unclear. This study investigated the regulatory pathway of tumors on appetite-inhibiting neurons (POMC) in the hypothalamus. Results showed that the tumor-expressed SEMA3D is positively related to POMC expression. Knocking out SEMA3D in mice increased food intake and body weight, and reduced muscle and fat catabolism. SEMA3D enhances POMC neuron activity by activating NRP2 and PlxnD1 expression. This research reveals that SEMA3D may play a vital role in appetite suppression and catabolic metabolism.
Article
Medicine, Research & Experimental
Doaa M. Samy, Dalia Kamal Mostafa, Doaa A. Abdelmonsif, Cherine A. Ismail, Passainte S. Hassaan
Summary: The study reveals the complex role of chemerin in appetite regulation, with uncertainty surrounding its mechanism and relationship with histamine and AMPK. New findings suggest that neurobiochemical pathways play a crucial role in appetite and obesity regulation, highlighting the importance of further research on chemerin for clinical implications.
Article
Cell Biology
Juliana Bezerra Medeiros de Lima, Chidera Ubah, Lucas Kniess Debarba, Iven Ayyar, Olesya Didyuk, Marianna Sadagurski
Summary: The hypothalamus plays a key role in controlling physiological functions and whole-body metabolism. Growth hormone (GH) and the GH receptor (GHR) are expressed in hypothalamic regions involved in regulating feeding and energy balance. SIRT1, a NAD(+)-dependent protein deacetylase, interacts with GHR signaling and plays a role in sensing nutrient availability in response to caloric restriction. In the arcuate nucleus (ARC) of the hypothalamus, GHR-expressing neurons also express SIRT1 and upregulate SIRT1 expression in response to fasting, revealing a novel interaction between GH and SIRT1 in fasting responses.
Article
Nutrition & Dietetics
Yermek Rakhat, Kentaro Kaneko, Lei Wang, Wanxin Han, Yutaka Seino, Daisuke Yabe, Toshihiko Yada
Summary: d-allulose can suppress hunger-associated feeding and inhibit hunger-promoting neurons in the hypothalamic arcuate nucleus.
Article
Neurosciences
Haofang E. Li, Mark A. Rossi, Glenn D. R. Watson, H. Gregory Moore, Min Tong Cai, Namsoo Kim, Katrina A. Vokt, Dongye Lu, Ryan A. Bartholomew, Ryan N. Hughes, Henry H. Yin
Summary: Choice behavior is influenced by temporal discounting, with hungry mice showing a preference for immediate food rewards while satiated mice are indifferent to reward delay. Activation of AgRP-expressing neurons in the hypothalamus or neuropeptide Y type 1 receptors in the BNST can induce temporal discounting, revealing a novel circuit that determines choice behavior.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Amelia M. Douglass, Jon M. Resch, Joseph C. Madara, Hakan Kucukdereli, Ofer Yizhar, Abhinav Grama, Masahito Yamagata, Zongfang Yang, Bradford B. Lowell
Summary: Fasting activates the HPA axis through the inhibition of GABAergic afferents by AgRP neurons in the PVH. This study reveals the neural basis for fasting-induced HPA axis activation and provides insights into the mechanisms underlying stress-induced HPA axis activation.
Article
Multidisciplinary Sciences
Amanda Rao, David Briskey, Carla dos Reis, Alistair R. Mallard
Summary: The study showed that Caralluma Fimbriata extract (CFE) can effectively reduce calorie intake, decrease waist circumference, maintain stable body weight, and have positive effects on body fat levels and BMI.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Monica Imbernon, Chiara Saponaro, Hans Christian Cederberg Helms, Manon Duquenne, Daniela Fernandois, Eleonora Deligia, Raphael G. P. Denis, Daniela Herrera Moro Chao, Sowmyalakshmi Rasika, Bart Staels, Francois Pattou, Frank W. Pfrieger, Birger Brodin, Serge Luquet, Caroline Bonner, Vincent Prevot
Summary: Liraglutide is transported to the hypothalamus by specialized ependymoglial cells called tanycytes, bypassing the blood-brain barrier. Silencing GLP1R in tanycytes or inhibiting tanycytic transport blocks the effects of liraglutide on hypothalamic neurons and its anti-obesity effects.
Article
Endocrinology & Metabolism
Surbhi, Gabor Wittmann, Malcolm J. Low, Ronald M. Lechan
Summary: The study showed that Rax(+) progenitors can generate POMC neurons in adult mice, leading to reduced body fat mass, improved glucose tolerance, increased insulin sensitivity, and decreased bodyweight, mitigating metabolic abnormalities.
MOLECULAR METABOLISM
(2021)
Article
Endocrinology & Metabolism
Sara Carmo-Silva, Marisa Ferreira-Marques, Clevio Nobrega, Mariana Botelho, Daniela Costa, Celia A. Aveleira, Stefan M. Pulst, Luis Pereira de Almeida, Claudia Cavadas
Summary: The ATXN2 gene is located in a trait locus for obesity and its knockout mice exhibit obesity and insulin resistance. This study shows that a high-fat diet decreases ataxin-2 levels in the hypothalamus and liver. Overexpression of ataxin-2 in the hypothalamus prevents high-fat diet-induced obesity and insulin resistance, and also rescues the circadian alterations observed in the knockout mice. These findings suggest that ataxin-2 plays a role in metabolic regulation and the circadian clock.
JOURNAL OF MOLECULAR ENDOCRINOLOGY
(2023)
Article
Clinical Neurology
Holger Hengel, Peter Martus, Jennifer Faber, Paola Giunit, Hector Garcia-Moreno, Nita Solanky, Thomas Klockgether, Kathrin Reetz, Bart P. van de Warrenburg, Magda M. Santana, Patrick Silva, Ines Cunha, Luis Pereira de Almeida, Dagmar Timmann, Jon Infante, Jeroen de Vries, Manuela Lima, Paula Pires, Khalaf Bushara, Heike Jacobi, Chiadi Onyike, Jeremy D. Schmahmann, Jeannette Hubener-Schmid, Matthis Synofzik, Ludger Schoels
Summary: This study reveals that non-motor symptoms such as sleep disturbance, restless legs syndrome, mild cognitive impairment, depression, bladder dysfunction, and pallhypesthesia are common among SCA3 patients and are significantly associated with disease severity and daily activities. Lifestyle factors like alcohol consumption, smoking, and physical activity may also be related to non-motor symptoms.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Rebekah Koppenol, Andre Conceicao, Ines T. Afonso, Ricardo Afonso-Reis, Rafael G. Costa, Sandra Tome, Diogo Teixeira, Joana Pinto da Silva, Jose Miguel Codesso, David V. C. Brito, Liliana Mendonca, Adriana Marcelo, Luis Pereira de Almeida, Carlos A. Matos, Clevio Nobrega
Summary: Koppenol et al. demonstrate that overexpression of G3BP1 reduces aggregation of ataxin-2 and ataxin-3 in cell models of SCA2 and SCA3. Lentiviral delivery of G3BP1 leads to improved motor function and neuropathology in preclinical models, suggesting its potential as a therapeutic target for polyQ disorders.
Review
Biochemistry & Molecular Biology
Elena Grao-Cruces, Carmen M. Claro-Cala, Sergio Montserrat de la Paz, Clevio Nobrega
Summary: Alzheimer's disease (AD), characterized by amyloid plaques and tau neurofibrillary tangles, is the most common form of dementia. Neuroinflammation and cellular stress have emerged as important factors in AD development and pathology. Chronic stress leads to the formation of stress granules (SGs), which have a protective role but can become pathological and neurotoxic, contributing to increased tau aggregation. Impaired lipid metabolism, specifically cholesterol efflux and lipid transport, is associated with a higher risk of AD. This review provides insight into the interplay between cellular stress, SGs, protein aggregation, and lipid metabolism in AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
David Rufino-Ramos, Patricia R. Albuquerque, Kevin Leandro, Vitor Carmona, Ines M. Martins, Rita Fernandes, Carina Henriques, Diana Lobo, Rosario Faro, Rita Perfeito, Liliana S. Mendonca, Dina Pereira, Celia M. Gomes, Rui Jorge Nobre, Luis Pereira de Almeida
Summary: Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is a common autosomal dominantly inherited ataxia caused by an over-repetition of the trinucleotide CAG within the ATXN3 gene. This study investigates the use of extracellular vesicles (EVs) as delivery vehicles for therapeutic miRNAs to treat MJD/SCA3. The results show that bioengineered EVs carrying miRNA-based silencing sequences effectively decrease mutant ATXN3 mRNA in cerebellar neurons and a mouse model.
Article
Clinical Neurology
Magda M. Santana, Laetitia S. Gaspar, Maria M. Pinto, Patrick Silva, Diana Adao, Dina Pereira, Joana Afonso Ribeiro, Ines Cunha, Jeannette Huebener-Schmid, Mafalda F. Raposo, Ana F. Ferreira, Jennifer Faber, Sandra Kuhs, Hector Garcia-Moreno, Kathrin Reetz, Andreas Thieme, Jon Infante, Bart P. C. van de Warrenburg, Paola Giunti, Olaf Riess, Ludger Schoels, Manuela Lima, Thomas Klockgether, Cristina Januario, Luis Pereira de Almeida
Summary: The European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative (ESMI) aims to establish the largest European trial-ready cohort for Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD), a common inherited ataxia. ESMI has focused on identifying biomarkers for SCA3/MJD to facilitate future intervention studies. To ensure accurate biomarker outcomes, ESMI standardized biosampling procedures. This consensus protocol may also be applicable to other neurodegenerative disorders, particularly ataxias, and marks the first step towards protocol harmonization in this field.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Behavioral Sciences
Catarina Carvalhas-Almeida, Joana Serra, Joaquim Moita, Claudia Cavadas, Ana Rita Alvaro
Summary: According to the World Health Organization, insomnia symptoms affect about one-third of the population, with chronic insomnia affecting around 10-15% of individuals. Chronic sleep deprivation and insomnia can lead to disruption in the internal synchronisation of biological clocks, resulting in negative health impacts. Glial cells, particularly microglia and astrocytes, play a role in circadian rhythm regulation and sleep/circadian regulation and overall healthy brain function. Understanding the interplay between glial cells and neurons is crucial in addressing sleep disorders and maintaining brain health.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Zoe A. Arnaut, Sara M. A. Pinto, Rafael T. Aroso, Anita S. Amorim, Catarina S. Lobo, Fabio A. Schaberle, Dina Pereira, Jisette Nunez, Sandra C. C. Nunes, Alberto A. C. C. Pais, Paulo Rodrigues-Santos, Luis Pereira de Almeida, Mariette M. Pereira, Luis G. Arnaut
Summary: The COVID-19 pandemic has highlighted our vulnerability to viruses, and traditional disinfection methods and existing medicines have limitations in combating SARS-CoV-2. In this study, a new photosensitizer for antimicrobial photodynamic therapy (aPDT) was synthesized to effectively inactivate SARS-CoV-2 at low concentration and intensity without toxicity to human cells. This chlorin-based aPDT offers fast, safe, and broad-spectrum photodisinfection with low risk of resistance.
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
(2023)
Article
Neurosciences
Mischa Uebachs, Philipp Wegner, Sebastian Schaaf, Simon Kugai, Heike Jacobi, Sheng-Han Kuo, Tetsuo Ashizawa, Juliane Fluck, Thomas Klockgether, Jennifer Faber
Summary: With SCAview, scientists can browse large datasets of common spinocerebellar ataxias intuitively and effortlessly. It offers various plot types to visualize data points and allows researchers to define subgroups and investigate them without technical effort.
Review
Neurosciences
Thomas Klockgether, Matthis Synofzik
Summary: To accelerate and facilitate clinical trials, the Ataxia Global Initiative (AGI) was established as a worldwide research platform for trial readiness in ataxias. One of AGI's major goals is the harmonization and standardization of outcome assessments. Clinical outcome assessments (COAs) that describe or reflect how a patient feels or functions are indispensable for clinical trials, but similarly important for observational studies and in routine patient care. The AGI working group on COAs has defined a set of data including a graded catalog of COAs that are recommended as a standard for future assessment and sharing of clinical data and joint clinical studies.
Review
Geriatrics & Gerontology
Catarina Carvalhas-Almeida, Claudia Cavadas, Ana Rita Alvaro
Summary: Despite age-related changes in sleep, a high percentage of older adults experience sleep dissatisfaction and chronic insomnia. Chronic insomnia, the most common sleep disorder worldwide, is expected to increase due to aging and obesity. This can lead to adverse health outcomes, promoting physical and cognitive decline and aggravating frailty in older adults. The link between chronic insomnia, hallmarks of aging, and frailty is discussed in this review, along with the potential effects of insomnia therapeutic approaches on cellular aging.
AGING CLINICAL AND EXPERIMENTAL RESEARCH
(2023)