Article
Neurosciences
Selena Gonzalez, Tyne L. M. McHugh, Tao Yang, Wassim Syriani, Stephen M. Massa, Frank M. Longo, Danielle A. Simmons
Summary: The study identified a new drug, PTX-BD10-2, that can help restore symptomatic neuron degeneration in an Alzheimer's disease mouse model and has neuroprotective effects on neurons derived from human induced pluripotent stem cells.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Nima Khalighinejad, Sanjay Manohar, Masud Husain, Matthew F. S. Rushworth
Summary: Decision-making involves choosing actions, as well as determining when and whether to initiate them. Different brain regions, such as DRN, BF, and ACC, contribute to different stages of decision-making, with 5-HT and ACh playing complementary roles.
Article
Biochemistry & Molecular Biology
Elissa Afram, Inger Lauritzen, Alexandre Bourgeois, Wejdane El Manaa, Eric Duplan, Mounia Chami, Audrey Valverde, Bauer Charlotte, Raphaelle Pardossi-Piquard, Frederic Checler
Summary: This study identifies eta CTF as a novel APP cleaving enzyme and suggests its involvement in the pathogenesis of Alzheimer's disease. The study also reveals the localization of eta CTF in Golgi and endosomes, as well as its presence in small extracellular vesicles. Furthermore, the expression of eta CTF in APP-null fibroblasts leads to A beta production, implicating its role in amyloid plaque formation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Geriatrics & Gerontology
Jose L. L. Martinez, Matthew D. D. Zammit, Nicole R. R. West, Bradley T. T. Christian, Anita Bhattacharyya
Summary: Down syndrome and Alzheimer's disease are both linked to cognitive impairment, with basal forebrain cholinergic neurons being vulnerable in both disorders, leading to memory loss and language disturbance. There are gaps in understanding the vulnerability of these neurons, limiting our ability to design effective interventions for individuals with DS and AD.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Masatomo Ishioh, Tsukasa Nozu, Saori Miyagishi, Sho Igarashi, Takuya Funayama, Masumi Ohhira, Toshikatsu Okumura
Summary: Intestinal barrier dysfunction, known as leaky gut, is associated with various diseases such as dementia and irritable bowel syndrome (IBS). This study revealed that basal forebrain cholinergic neurons (BFCNs) improve leaky gut through adenosine A2B signaling and the vagal pathway. Additionally, BFCNs mediate the improvement of intestinal barrier function induced by orexin or butyrate.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ryan Keable, Shangfeng Hu, Grant Pfundstein, Irina Kozlova, Feifei Su, Ximing Du, Hongyuan Yang, Jenny Gunnersen, Melitta Schachner, Iryna Leshchyns'ka, Vladimir Sytnyk
Summary: The association between NCAM2 and BACE1 promotes the targeting of BACE1 to endosomes, thereby regulating its activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yingwei Zheng, Sijue Tao, Yue Liu, Jingjing Liu, Liping Sun, Yawen Zheng, Yu Tian, Peng Su, Xutao Zhu, Fuqiang Xu
Summary: This study reveals the projections of basal forebrain cholinergic neurons and their role in olfactory associative learning. The HMSc-dHIP cholinergic circuit plays a crucial role in regulating olfactory associative learning.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Panna Hegedus, Katalin Sviatko, Balint Kiraly, Sergio Martinez-Bellver, Balazs Hangya
Summary: Basal forebrain cholinergic neurons have an important role in associative learning and processing stimuli that predict future outcomes. This study used calcium imaging and spiking recordings to investigate the impact of outcome probabilities on these neurons in mice. The results showed that the cholinergic neurons responded more strongly to sensory cues that were often paired with reward, and reward delivery activated the neurons, with surprising rewards generating a stronger response. The findings suggest that the cholinergic neurons differentially weigh predictions of positive and negative reinforcement, reflecting the relative salience of appetitive and aversive outcomes.
Article
Biology
Blaise Robert, Eyal Y. Kimchi, Yurika Watanabe, Tatenda Chakoma, Miao Jing, Yulong Li, Daniel B. Polley
Summary: Research shows that basal forebrain cholinergic neurons have different functional characteristics in different regions, broadcasting diverse modulatory signals to downstream brain regions.
Article
Neurosciences
Gaq Tu, Adel Halawa, Xiaotian Yu, Samuel Gillman, Kaori Takehara-Nishiuchi
Summary: Acetylcholine controls arousal, attention, and learning through regulating cortical excitability and plasticity. Recent research found that cholinergic neurons emit precise signals about aversive outcomes. This study manipulated cholinergic terminals in the mPFC and discovered that phasic cholinergic signaling plays a crucial role in aversive associative learning.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Environmental Sciences
Emma Sola, Paula Moyano, Andrea Flores, Jimena Garcia, Jose Manuel Garcia, Maria Jose Anadon, Maria Teresa Frejo, Adela Pelayo, Maria de la Cabeza Fernandez, Javier del Pino
Summary: Cadmium exposure damages basal forebrain cholinergic neurons and disrupts thyroid hormone levels, leading to cognitive disabilities. These findings contribute to understanding the mechanisms by which cadmium induces cognitive impairments, and offer potential therapeutic targets.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2022)
Article
Clinical Neurology
Mikahela A. Lopez-Morales, Iris Escobar, Isabel Saul, Charles W. Jackson, Fernando J. Ferrier, Eric A. Fagerli, Ami P. Raval, Kunjan R. Dave, Miguel A. Perez-Pinzon
Summary: This study reveals that focal cerebral ischemia leads to the death of cholinergic neurons in memory-relevant nuclei of the basal forebrain, and resveratrol preconditioning can prevent this cell loss, improve memory performance, and preserve the functionality of memory-processing brain structures.
Article
Medicine, Research & Experimental
Yong-Xia Xu, Can Wang, Xiao-Die Li, Wen-Lu Guo, Guo-Ying Liu, Hua-Bing Zhang, Yan Sun, De-Fa Zhu, Qi Xu
Summary: Cognitive dysfunction is common in hypothyroid patients, even after sufficient levothyroxine replacement therapy. Cholinergic neurons play a role in this cognitive impairment. Activating the BF cholinergic neurons improves cognitive function through the BF-PFC and BF-hippocampus pathways.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biology
Didier De Saint Jan
Summary: This study investigated the role of basal forebrain (BF) inputs in modulating activity of different subtypes of periglomerular (PG) interneurons in the olfactory bulb (OB). The results showed that GABAergic BF inputs effectively inhibited PG cell firing, while cholinergic inputs excited a previously overlooked PG cell subtype. These findings highlight the importance of external inputs in synaptic inhibition in the OB.
Article
Biochemistry & Molecular Biology
Laura Schnoeder, Inge Tomic, Laura Schwindt, Dominic Helm, Mandy Rettel, Walter Schulz-Schaeffer, Elmar Krause, Jens Rettig, Klaus Fassbender, Yang Liu
Summary: Deficiency of p38 alpha-MAPK in neurons leads to increased retrograde transportation of BACE1 in axons, shifting it from axonal terminals to lysosomes in the cell body, which exacerbates amyloid deposition in the brain of Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Stephen D. Ginsberg, Thomas A. Neubert, Sahil Sharma, Chander S. Digwal, Pengrong Yan, Calin Timbus, Tai Wang, Gabriela Chiosis
Summary: The article discusses the relationship between stressor-induced protein interactome network perturbations and the formation of pathologic scaffolds, proposing how epichaperomics can reliably obtain context-dependent interactomes to advance the definition, understanding, and control of complex disease interactome networks.
Editorial Material
Neurosciences
John J. Alam, Ralph A. Nixon
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Neurosciences
John S. Beck, Zachary Madaj, Calvin T. Cheema, Betul Kara, David A. Bennett, Julie A. Schneider, Marcia N. Gordon, Stephen D. Ginsberg, Elliott J. Mufson, Scott E. Counts
Summary: The mechanisms of Alzheimer's disease and mild cognitive impairment involve dysregulation of multiple molecular pathways. This study analyzed gene expression patterns and found that insulin signaling was associated with clinical diagnosis, potentially playing a role in disease onset. Additionally, the platelet-endothelium-leucocyte cell adhesion pathways and hypoxia-oxidative stress were linked to neuropathological diagnostic criteria, potentially impacting disease progression and clinical presentation.
Correction
Neurosciences
Melissa J. Alldred, Sai C. Penikalapati, Sang Han Lee, Adriana Heguy, Panos Roussos, Stephen D. Ginsberg
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Ju-Hyun Lee, Dun-Sheng Yang, Chris N. Goulbourne, Eunju Im, Philip Stavrides, Anna Pensalfini, Han Chan, Cedric Bouchet-Marquis, Cynthia Bleiwas, Martin J. Berg, Chunfeng Huo, James Peddy, Monika Pawlik, Efrat Levy, Mala Rao, Mathias Staufenbiel, Ralph A. Nixon
Summary: This study reveals unique autophagy dysregulation within neurons in Alzheimer's disease mouse models, particularly deficient autolysosome acidification, leading to the accumulation of autophagic vacuoles and the formation of flower-like structures called "PANTHOS," which may contribute to the development of senile plaques in Alzheimer's disease.
NATURE NEUROSCIENCE
(2022)
Article
Neurosciences
Yann Dromard, Margarita Arango-Lievano, Amelie Borie, Maheva Dedin, Pierre Fontanaud, Joan Torrent, Michael J. Garabedian, Stephen D. Ginsberg, Freddy Jeanneteau
Summary: Aberrant cortisol and activation of the glucocorticoid receptor (GR) contribute to the progression of Alzheimer's disease (AD). Disrupting BDNF-dependent GR phosphorylation exacerbates the detrimental effects of AD in mice, while downregulated BDNF signaling and upregulated cortisol pathway activation are observed in postmortem AD subjects. These findings suggest that targeting the neurotrophin-mediated GR phosphorylation pathway could be a novel approach to treat AD dementia.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Cell Biology
Mala Rao, Sandipkumar Darji, Philip H. Stavrides, Chris N. Goulbourne, Asok Kumar, Dun-Sheng Yang, Lang Yoo, James Peddy, Ju-Hyun Lee, Aidong Yuan, Ralph A. Nixon
Summary: This study reveals the important role of autophagy in the degradation of neurofilament proteins in neurons, which may regulate the size of axon cytoskeleton and the responses of the neurofilament cytoskeleton to injury and disease.
Article
Neurosciences
Aidong Yuan, Ralph A. Nixon
Summary: Neurofilament and tau proteins are involved in regulating stability and functions of the microtubule network in axons, axonal transport, and learning and memory. Their expression is regulated at the transcriptional and posttranscriptional levels, with RNA-binding proteins and microRNAs playing important roles in their regulation through the 3'-untranslated regions of their mRNA.
BRAIN RESEARCH BULLETIN
(2023)
Article
Immunology
Anne-Laure Hemonnot-Girard, Cedric Meersseman, Manuela Pastore, Valentin Garcia, Nathalie Linck, Catherine Rey, Amine Chebbi, Freddy Jeanneteau, Stephen D. Ginsberg, Joel Lachuer, Christelle Reynes, Francois Rassendren, Helene Hirbec
Summary: This study used cell-specific laser capture microdissection and RNA-seq analysis to isolate and analyze plaque-associated and plaque-distant microglia in an AD mouse model. The results showed distinct transcriptional differences between these two microglial subtypes, indicating their different roles in AD progression.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Pharmacology & Pharmacy
Stephen D. Ginsberg, Sahil Sharma, Larry Norton, Gabriela Chiosis
Summary: Diseases are complex manifestations of changes in protein-protein interaction networks caused by stressors, genetics, environment, and their combinations, affecting molecular interactions and disrupting the normal function of cells, tissues, and organisms. Disrupting epichaperomes, which enable dysfunctional rewiring of these networks, is proposed as a mechanism for reverting context-specific dysfunction to a normative state. This has potential implications for precision medicine in detecting and treating complex diseases like cancer and neurodegenerative disorders.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Melissa J. Alldred, Harshitha Pidikiti, Adriana Heguy, Panos Roussos, Stephen D. Ginsberg
Summary: Basal forebrain cholinergic neuron (BFCN) degeneration is a characteristic of Down syndrome (DS) and Alzheimer's disease (AD). Maternal choline supplementation (MCS) has been shown to attenuate the degeneration of BFCNs in a mouse model, suggesting a potential therapeutic effect for DS and AD.
Article
Medicine, General & Internal
Melissa J. J. Alldred, Stephen D. D. Ginsberg
Summary: Single-cell and single-population RNA sequencing is a valuable tool in studying the transcriptomic profiles of neurons based on their spatial localization. Laser capture microdissection and RNA purification allow for the isolation of desired neurons for downstream analysis, such as differential gene expression and pathway exploration.
JOURNAL OF CLINICAL MEDICINE
(2023)
Editorial Material
Neurosciences
John J. Alam, Ralph A. Nixon
MOLECULAR NEURODEGENERATION
(2023)
Article
Clinical Neurology
Christy M. Kelley, Stephen D. Ginsberg, Winnie S. Liang, Scott E. Counts, Elliott J. Mufson
Summary: RNA-seq analysis of the posterior cingulate cortex in aged individuals revealed differential gene expression and transcription factor binding sites between different Braak stages, suggesting a potential role for synaptic genes in cognitive resilience.
BRAIN COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Nicole Beaulieu Perez, Allison A. Vorderstrasse, Gary Yu, Gail D'Eramo Melkus, Fay Wright, Stephen D. Ginsberg, Cindy A. Crusto, Yan Sun, Jacquelyn Y. Taylor
Summary: In African American women, the associations between age acceleration, depressive symptoms, and cardiometabolic traits are complex and may be influenced by factors other than age acceleration. Factors other than age acceleration may explain the connection between depressive symptoms and cardiometabolic traits in this population. African American women with cardiometabolic traits may be at increased risk of accelerated aging.
EPIGENETICS INSIGHTS
(2022)
Article
Geriatrics & Gerontology
Sarah N. Kraeutner, Cristina Rubino, Jennifer K. Ferris, Shie Rinat, Lauren Penko, Larissa Chiu, Brian Greeley, Christina B. Jones, Beverley C. Larssen, Lara A. Boyd
Summary: This study examined the age-related changes in brain function and baseline brain structure that support motor skill acquisition. The findings showed that older adults experienced decreases in functional connectivity during motor skill acquisition, while younger adults experienced increases. Additionally, regardless of age group, lower baseline microstructure in a frontoparietal tract was associated with slower motor skill acquisition.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Karen Nuytemans, Farid Rajabli, Melissa Jean-Francois, Jiji Thulaseedhara Kurup, Larry D. Adams, Takiyah D. Starks, Patrice L. Whitehead, Brian W. Kunkle, Allison Caban-Holt, Jonathan L. Haines, Michael L. Cuccaro, Jeffery M. Vance, Goldie S. Byrd, Gary W. Beecham, Christiane Reitz, Margaret A. Pericak-Vance
Summary: This study conducted genetic research on African American AD families and identified a significant linkage signal associated with AD, highlighting the importance of diverse population-level genetic data in understanding the genetic determinants of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Kazuya Suwabe, Ryuta Kuwamizu, Kazuki Hyodo, Toru Yoshikawa, Takeshi Otsuki, Asako Zempo-Miyaki, Michael A. Yassa, Hideaki Soya
Summary: Physical exercise has a positive impact on hippocampal memory decline with aging. Recent studies have shown that even light exercise can improve memory and this improvement is mediated by the ascending arousal system. This study aimed to investigate the effects of light-intensity exercise on hippocampal memory function in healthy older adults and found that pupil dilation during exercise played a role in the memory improvement.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Ajay Sood, Ana Werneck Capuano, Robert Smith Wilson, Lisa Laverne Barnes, Alifiya Kapasi, David Alan Bennett, Zoe Arvanitakis
Summary: The objective of this study was to explore the impact of metformin on cognition and brain pathology. The results showed that metformin users had slower decline in global cognition, episodic memory, and semantic memory compared to non-users. However, the relationship between metformin use and certain brain pathology remains uncertain.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Brian N. Lee, Junwen Wang, Molly A. Hall, Dokyoon Kim, Shana D. Stites, Li Shen
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. This study analyzed participants from the Alzheimer's Disease Neuroimaging Initiative and found differential associations between cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes, as well as variations between sexes. These findings suggest that sex differences may play a role in the development of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Thomas T. Austin, Christian L. Thomas, Ben Warren
Summary: This study investigated the effects of age on the robustness and resilience of auditory system using the desert locust. The researchers found that gene expression changes were mainly influenced by age rather than noise exposure. Both young and aged locusts were able to recover their auditory nerve function within 48 hours of noise exposure, but the recovery of transduction current magnitude was impaired in aged locusts. Key genes responsible for robustness to noise exposure in young locusts and potential candidates for compensatory mechanisms in auditory neurons of aged locusts were identified.
NEUROBIOLOGY OF AGING
(2024)
