Review
Biochemistry & Molecular Biology
Xinrong Li, Shih-Chi Chen, Jacque Pak Kan Ip
Summary: This article explores the role of different cells in the brain, such as astrocytes, microglia, and vascular cells, in interacting with neurons and contributing to cognitive impairment in diseases. Specifically, it focuses on the importance of synaptic loss and dysfunction in Alzheimer's disease (AD) and how miRNAs can be essential regulators in this process. The article also discusses the potential of miRNA-related biomarkers, therapeutics, and emerging imaging technologies for AD research.
Article
Neurosciences
Jessica A. Lawrence, Patricia Aguilar-Calvo, Daniel Ojeda-Juarez, Helen Khuu, Katrin Soldau, Donald P. Pizzo, Jin Wang, Adela Malik, Timothy F. Shay, Erin E. Sullivan, Brent Aulston, Seung Min Song, Julia A. Callender, Henry Sanchez, Michael D. Geschwind, Subhojit Roy, Robert A. Rissman, JoAnn Trejo, Nobuyuki Tanaka, Chengbiao Wu, Xu Chen, Gentry N. Patrick, Christina J. Sigurdson
Summary: Endolysosomal defects, including the reduction of Hrs and STAM1, exacerbate synaptic derangements and accelerate neurodegeneration in prion-infected brains. Depletion of neuronal Hrs leads to increased surface levels of PrPC, contributing to the rapidly advancing disease through neurotoxic signaling. The findings highlight the importance of proteostatic pathways and synaptic integrity in prion diseases.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Ye Wang, Amy K. Y. Fu, Nancy Y. Ip
Summary: In the adult hippocampus, astrocytes, the most common glial cells, play a crucial role in regulating synaptic plasticity. Astrocytes are highly heterogeneous in response to changes in neuronal activity and can modulate synaptic communication through various pathways, ultimately influencing memory performance and cognitive functions. Dysregulation of astrocytic signaling can lead to hippocampal circuit dysfunction and cognitive impairment, as observed in conditions like Alzheimer's disease.
Article
Neurosciences
Bruno G. Frenguelli
Summary: This article discusses the Neuropharmacology Special Issue on 'Glutamate Receptors -The Glutamatergic Synapse', focusing on the importance of glutamate as a neurotransmitter and the central role of the glutamatergic synapse in neuronal signaling.
Review
Neurosciences
Damaris Nieves Torres, Sang H. Lee
Summary: Conventional inter-neuronal communication is wired and occurs through chemical synapses, but recent studies suggest that neurons can also communicate wirelessly through small extracellular vesicles (EVs). These small EVs, including exosomes, contain various signaling molecules and can be absorbed by recipient cells. Neuronal small EVs have been found to affect multiple neuronal functions. This volume transmission mediated by small EVs is important for activity-dependent changes in neuronal function and the regulation of local circuitry. In this review, recent discoveries and the potential scope of small EV-mediated inter-neuronal signaling are summarized.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Snjezana Radulovic, Sowmya Sunkara, Christa Maurer, Gerd Leitinger
Summary: Recent research suggests that neurodegeneration may stem from an imbalance in synaptic structural components, particularly inhibitory synapses communicating via neurotransmitters like GABA and glycine. This imbalance can deeply affect the ability of neurons to communicate effectively, leading to progressive failure of synaptic plasticity and memory. New high-resolution visualization methods offer promising opportunities to explore the involvement of inhibitory synapses in neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Cell Biology
Young Mi Oh, Seong Won Lee, Andrew S. Yoo
Summary: Huntington disease (HD) is an inherited neurodegenerative disease that manifests in adulthood. The mechanism behind how aging triggers neurodegeneration in HD patients is still unknown. By modeling the disease progression of HD using medium spiny neurons (MSNs) generated from fibroblasts of HD patients at different stages, researchers found a decline in cellular functions such as autophagy/macroautophagy and onset of neurodegeneration with age. The study also identified that HD-MSNs have increased chromatin accessibility and upregulated MIR29B-3p, which represses STAT3 and leads to HD-MSN degeneration. The findings highlight the dysregulation of microRNA and autophagy associated with MSN degeneration in HD, and propose potential approaches for protecting MSNs by enhancing autophagy.
Article
Pharmacology & Pharmacy
Kaori Ishikawa, Satoshi Yamamoto, Satoko Hattori, Naoya Nishimura, Hirokazu Matsumoto, Tsuyoshi Miyakawa, Kazuto Nakada
Summary: This study generated a novel mouse model expressing a dominant-negative form of MFN2 and found that continuous expression of the mutated MFN2 resulted in hyperactivity and cognitive impairments, while transient expression showed different phenotypes. Abnormal mitochondrial dynamics can lead to stress, triggering neuronal degeneration. Normalization of mitochondrial dynamics may prevent neurodegeneration. The mouse model created in this study can serve as a useful tool for investigating neuronal plasticity mechanisms and neurodegeneration.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Sandra Dubes, Anais Soula, Sebastien Benquet, Beatrice Tessier, Christel Poujol, Alexandre Favereaux, Olivier Thoumine, Mathieu Letellier
Summary: This study reveals the molecular mechanism of synapse-specific homeostatic plasticity. The synaptic tagging mechanism, driven by synaptopodin, regulates the enhancement of synaptic strength in a synapse-specific manner. This finding shifts the understanding of homeostatic plasticity towards the idea that the ability for changes depends on the functional and biochemical state of individual synapses.
Article
Cell Biology
Julia Solana-Balaguer, Genis Campoy-Campos, Nuria Martin-Flores, Leticia Perez-Sisques, Laia Sitja-Roqueta, Melike Kucukerden, Ana Gamez-Valero, Albert Coll-Manzano, Eulalia Marti, Esther Perez-Navarro, Jordi Alberch, Jordi Soriano, Merce Masana, Cristina Malagelada
Summary: Extracellular vesicles, specifically neuron-derived EVs, play a crucial role in intercellular communication within the central nervous system. These EVs carry signaling molecules and exert a trophic effect on neurons, influencing synaptic events and promoting neuronal protection.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Biochemistry & Molecular Biology
Przemyslaw A. Stempor, Dror Avni, Raya Leibowitz, Yechezkel Sidi, Maria Stepien, Tomasz Dzieciatkowski, Paula Dobosz
Summary: Personalised medicine is the future of patient care, particularly in diseases like cancer. MicroRNAs play crucial roles in bladder cancer pathogenesis, treatment response, and immune system interactions, highlighting their potential for personalized medicine interventions. Analysis of microRNA and gene expression data has identified several potential candidates for targeted therapeutics and diagnostics in bladder cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Zhendong Feng, Lopamudra Saha, Clio Dritsa, Qi Wan, Oleg O. O. Glebov
Summary: The function of the central nervous system is strongly influenced by temperature. This study reveals that hypothermia and hyperthermia trigger bidirectional re-organization of presynaptic architecture in hippocampal neurons, resulting in synaptic strengthening and weakening respectively. Hypothermia also remodels inhibitory postsynaptic scaffold, leading to enlarged sparse synapses enriched with GABAA receptors.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Katarzyna M. Grochowska, Marit Sperveslage, Rajeev Raman, Antonio V. Failla, Dawid Glow, Christian Schulze, Laura Laprell, Boris Fehse, Michael R. Kreutz
Summary: The complex morphology of neurons presents a challenge for proteostasis, but recent studies have shown that mature lysosomes can be found in dendrites and release their content through fusion with the plasma membrane. These dendritic lysosomes are heterogeneous in composition and only those containing LAMP2A and LAMP2B exhibit activity-dependent motility. They dock near NMDAR receptors via an association with SAP102/Dlg3, and NMDAR activation decreases lysosome motility and promotes fusion with the membrane. Chaperone-mediated autophagy supplies content that is released through lysosome exocytosis, enabling local disposal of aggregation-prone proteins.
Article
Neurosciences
Sergio Hernandez-Diaz, Saurav Ghimire, Irene Sanchez-Mirasierra, Carla Montecinos-Oliva, Jef Swerts, Sabine Kuenen, Patrik Verstreken, Sandra-Fausia Soukup
Summary: Synapses are essential for neuronal communication and brain function, and autophagy plays a critical role in maintaining synaptic homeostasis. Synaptic dysfunction is a characteristic feature of neurodegenerative diseases, including Parkinson's disease. This study identifies Endophilin-B (EndoB) as a novel regulator of synaptic autophagy in health and disease. The findings demonstrate that EndoB is required for autophagosome biogenesis at the synapse and loss of EndoB impairs autophagy induction promoted by the PD-associated mutation LRRK2(G2019S). Furthermore, EndoB is necessary for preventing neuronal loss and it plays a role in synaptic contact formation.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
Yi Wang, Ping Yuan, Lu Ding, Jie Zhu, Xinrui Qi, Yanyan Zhang, Yunxia Li, Xiaohuan Xia, Jialin C. C. Zheng
Summary: This study investigated the miRNA profiles in serum-derived EVs from AD, MCI patients, and healthy individuals. Differential expression patterns of CEmiRs were observed and classified into 10 clusters. By analyzing the predicted targets of these differentially expressed CEmiRs, our study revealed the temporal regulation of complex and precise signaling networks on AD pathogenesis.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Erica de Sousa, Marilia Ines Movio, Theo Henrique de Lima-Vasconcellos, Gabrieli Bovi dos Santos, Talita dos Santos Gomes, Lais Takata Walter, Daniela Almeida da Silva, Tiago Rodrigues, Giselle Cerchiaro, Alexandre Hiroaki Kihara
Summary: The regulation of VDAC1 plays a crucial role in neuronal survival and the activation of microglial cells. Inhibition of VDAC1 oligomerization has neuroprotective effects and prevents microglial polarization. These findings suggest that VDAC1 could be a potential therapeutic target in neuronal disorders.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Peter J. Schuette, Juliane M. Ikebara, Sandra Maesta-Pereira, Anita Torossian, Ekayana Sethi, Alexandre H. Kihara, Jonathan C. Kao, Fernando M. C. Reis, Avishek Adhikari
Summary: This study investigates the neural activity of glutamatergic and GABAergic neurons in the CA1 region of the hippocampus during environmental changes. The results show that GABAergic neurons have decreased remapping compared to glutamatergic neurons, while the spatial encoding of glutamatergic neurons remains stable across multiple days. However, GABAergic neurons are less likely to remain active and exhibit consistent place coding across recording days.
SCIENTIFIC REPORTS
(2022)
Review
Cell Biology
Cayo Almeida, Renan Paschoalino Pongilio, Marilia Ines Movio, Guilherme Shigueto Vilar Higa, Rodrigo Ribeiro Resende, Jianxiong Jiang, Erika Reime Kinjo, Alexandre Hiroaki Kihara
Summary: Temporal lobe epilepsy (TLE) is associated with oxidative stress and neuroinflammation, which involve various types of cells. Molecules involved in oxidative stress response and neuroinflammation have been proposed as potential targets for TLE treatment. This review examines the roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase 2 (NOX2) and Myeloid Differentiation Primary Response 88 (MyD88) in astrocytes, microglia, and neurons during epileptogenesis. The use of single-cell RNA sequencing, transgenic technologies, and viral serotypes with specific promoters is also discussed for studying gene expression in different cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Marilia Ines Movio, Theo Henrique de Lima-Vasconcellos, Gabrieli Bovi dos Santos, Marcela Bermudez Echeverry, Elisabetta Colombo, Leonardo S. Mattos, Rodrigo Ribeiro Resende, Alexandre Hiroaki Kihara
Summary: Human-induced pluripotent stem cells (hiPSCs) have revolutionized the study of neurodegenerative diseases, including retinal dystrophies. In vitro modeling of retinal diseases using hiPSCs has offered new insights and possibilities for early diagnosis of conditions like Alzheimer's disease (AD) and Parkinson's disease (PD). This review highlights recent progress in the field and emphasizes the potential of retinal organoids obtained from potential patients to evaluate disease-related changes long before symptoms appear.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Lucas Felipe de Oliveira, Daniel Mendes Filho, Bruno Lemes Marques, Giovana Figueiredo Maciel, Ricardo Cambraia Parreira, Jose Rodrigues do Carmo Neto, Priscilla Elias Ferreira Da Silva, Rhanoica Oliveira Guerra, Marcos Vinicius da Silva, Helton da Costa Santiago, Alexander Birbrair, Alexandre H. Kihara, Valdo Jose Dias da Silva, Talita Glaser, Rodrigo R. Resende, Henning Ulrich
Summary: Infectious diseases have significant impacts on human health globally, and there is an urgent need for a better understanding. In vitro and in vivo infection models have made significant contributions to our current knowledge of these diseases. Organoids simulate tissue architecture and function, recapitulating many characteristics of human diseases and elucidating host-pathogen interactions in various systems. In this article, we discuss the applicability of organoid technology in modeling pathogenesis, host response, and features, which can be explored for the development of preventive and therapeutic treatments.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Bruno L. Marques, Giovana Figueiredo Maciel, Marcello R. Brito Junior, Lucas D. Dias, Sergio Scalzo, Anderson K. Santos, Alexandre Hiroaki Kihara, Helton da Costa Santiago, Ricardo C. Parreira, Alexander Birbrair, Rodrigo R. Resende
Summary: As the world population's life expectancy increases, more efficient therapies are needed for neurodegenerative disorders common in old age. Neural stem cells (NSCs) play a crucial role in the development and functioning of the nervous system and have broad therapeutic applications for neurodegenerative diseases. Understanding the mechanisms that govern NSC self-renewal, differentiation, and cell signaling is essential for these therapies.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Anderson K. Santos, Sergio Scalzo, Raysa T. V. de Souza, Pedro H. G. Santana, Bruno L. Marques, Lucas F. Oliveira, M. Filho Daniel, Alexandre Hiroaki Kihara, Helton da Costa Santiago, Ricardo C. Parreira, Alexander Birbrair, Henning Ulrich, Rodrigo R. Resende
Summary: Organoid development and organ-on-a-chip are technologies that utilize stem cells to create 3D multicellular structures resembling organs and tissues in vivo. They can be strategically employed for disease modeling, drug screening, and host-pathogen studies.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Luciana Simoes Rafagnin Marinho, Gabrielly Maria Denadai Chiarantin, Juliane Midori Ikebara, Debora Sterzeck Cardoso, Theo Henrique de Lima-Vasconcellos, Guilherme Shigueto Vilar Higa, Mariana Sacrini Ayres Ferraz, Roberto De Pasquale, Silvia Honda Takada, Fabio Papes, Alysson R. Muotri, Alexandre Hiroaki Kihara
Summary: The use of antidepressants during pregnancy can benefit the mother but has potential negative effects on neurodevelopment. In utero exposure to SSRIs has been linked to developmental abnormalities and an increased risk of ASD and ADHD. The development of hiPSC methods and cerebral organoids provides a valuable tool for studying the effects of these compounds on neurodevelopment. Single-cell RNA sequencing and electrophysiological measurements can be used to analyze the impact of antidepressants on developing neurons.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Behavioral Sciences
F. S. Borges, E. C. Gabrickc, P. R. Protachevicz, G. S. V. Higa, E. L. Lameu, P. X. R. Rodriguez, M. S. A. Ferraz, J. D. Szezech Jr, A. M. Batista, A. H. Kihara
Summary: Neuronal synchronization is crucial for brain communication and learning, but changes in connectivity can lead to hyper-synchronized states associated with epileptic seizures. The ARC protein is linked to synaptic alterations and epilepsy. Intense ARC immunoreactive neurons (IAINs) with increased connectivity and conductance are observed during status epilepticus, potentially contributing to abnormal seizure activity. This study investigates how IAINs connectivity influences firing patterns and synchronization. Synchronized burst patterns and intermittent up and down activities are observed in neural networks with increased IAINs connectivity. Optogenetics control effectively suppresses synchronized bursts when IAINs are targeted, highlighting their important role in both generating and suppressing highly synchronous activities.
EPILEPSY & BEHAVIOR
(2023)
Editorial Material
Biochemistry & Molecular Biology
Zhi Dong Zhou, Alexandre Hiroaki Kihara
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Miguel Tabanez, Ilma R. Santos, Juliane M. Ikebara, Mariana L. M. Camargo, Bianca A. Dos Santos, Bruna M. Freire, Bruno L. Batista, Silvia H. Takada, Rosanna Squitti, Alexandre H. Kihara, Giselle Cerchiaro
Summary: As people age, they become more susceptible to neurodegenerative illnesses such as Alzheimer's disease. This study found that the antioxidant hydroxytyrosol can regulate metal levels and improve learning performance in a rat model of AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Rafael Bandeira Fabres, Debora Sterzeck Cardoso, Brian Aranibar Aragon, Bruna Petrucelli Arruda, Pamela Pinheiro Martins, Juliane Midori Ikebara, Alexander Drobyshevsky, Alexandre Hiroaki Kihara, Luciano Sturmer de Fraga, Carlos Alexandre Netto, Silvia Honda Takada
Summary: Oxygen deprivation is a major cause of mortality and morbidity in newborns, especially preterm infants. Surviving infants may develop neuropsychological pathologies, including learning difficulties and cerebral palsy. White matter injury, primarily affecting the myelin sheath, leads to long-term cognitive and motor impairments. Recent research has focused on the potential therapeutic targets of oligodendrocytes and myelination to minimize the impact of oxygen deprivation on the central nervous system. Furthermore, sexual dimorphism may influence neuroinflammation and white matter injury induced by oxygen deprivation.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2023)
Article
Physics, Fluids & Plasmas
Mariana Sacrini Ayres Ferraz, Alexandre Hiroaki Kihara
Summary: The vast amount of available data requires efforts to extract meaningful information. In this study, different measurements of information entropy in binary series with temporal correlations are compared. A new measure called the binary permutation index (BPI) is proposed, which efficiently discriminates patterns in the series and offers advantages over previous methods.