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
Clinical Neurology
Claire Andre, Marie-eve Martineau-Dussault, Veronique Daneault, Helene Blais, Sonia Frenette, Dominique Lorrain, Carol Hudon, Celyne Bastien, Dominique Petit, Alexandre Lafreniere, Cynthia Thompson, Jacques Montplaisir, Nadia Gosselin, Julie Carrier
Summary: This study investigated the associations between the volume of basal forebrain nuclei and REM sleep characteristics, and the impact of cognitive status on these links. The findings suggest that REM sleep disturbances may be an early manifestation of the degeneration of the basal forebrain cholinergic system, especially in participants with mild memory deficits.
ALZHEIMERS RESEARCH & THERAPY
(2023)
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
Neurosciences
Mihai Avram, Michel J. Grothe, Lena Meinhold, Claudia Leucht, Stefan Leucht, Stefan Borgwardt, Felix Brandl, Christian Sorg
Summary: Research suggests that patients with schizophrenia have lower volumes of cholinergic basal forebrain nuclei, which are associated with cognitive deficits, specifically in attention.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Sweyta Lohani, Andrew H. Moberly, Hadas Benisty, Boris Landa, Miao Jing, Yulong Li, Michael J. Higley, Jessica A. Cardin
Summary: This study investigates the relationship between fluctuations in behavioral state and brain activity, particularly focusing on the role of acetylcholine in the neocortex. The findings suggest that different levels of arousal in distinct behavioral states are linked to dynamic patterns of cholinergic modulation and network correlations.
NATURE NEUROSCIENCE
(2022)
Article
Neuroimaging
Christine Kindler, Neeraj Upadhyay, Zeynep Bendella, Franziska Dorn, Vera C. Keil, Gabor C. Petzold
Summary: This study explored the influence of white matter hyperintensities on the degeneration of cholinergic basal forebrain structures in Alzheimer's disease (AD). The results showed that the volumes of cholinergic basal forebrain structures were significantly smaller in AD patients compared to controls, but there was no clear correlation between white matter hyperintensity burden and cholinergic basal forebrain structure volumes.
NEUROIMAGE-CLINICAL
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Piao Zhang, Siming Rong, Chentao He, Yan Li, Xiaohong Li, Zhenzhen Chen, Kun Nie, Limin Wang, Lijuan Wang, Yuhu Zhang
Summary: This study investigated the cholinergic basal forebrain pathology in Parkinson's disease with mild cognitive impairment (PD-MCI) and found that functional connectivity changes are frequency-specific, providing new insights into the functional alterations within the cholinergic system in cognitive impairment.
QUANTITATIVE IMAGING IN MEDICINE AND SURGERY
(2023)
Article
Clinical Neurology
Julia Schumacher, Nicola J. Ray, Calum A. Hamilton, Paul C. Donaghy, Michael Firbank, Gemma Roberts, Louise Allan, Rory Durcan, Nicola Barnett, John T. O'Brien, John-Paul Taylor, Alan J. Thomas
Summary: Patients with dementia with Lewy bodies and Alzheimer's disease exhibited early degeneration of the cholinergic nucleus basalis of Meynert. However, it remains unknown how white matter projections between the nucleus basalis of Meynert and the cortex are affected in neurodegenerative diseases. This study utilized diffusion-weighted imaging to investigate the white matter pathways originating from the nucleus basalis of Meynert in patients with different cognitive conditions. The results demonstrated that the integrity of these pathways is associated with cognition and attention, and might serve as an early indicator for the risk of dementia conversion in individuals with mild cognitive impairment.
Article
Clinical Neurology
Nicola J. J. Ray, Prabesh Kanel, Nicolaas I. I. Bohnen
Summary: Structural imaging of the cholinergic basal forebrain may provide a biomarker for cholinergic system integrity in Parkinson's disease. This study validates the correlation between cholinergic basal forebrain morphometry and vesicular acetylcholine transporter in a large Parkinson's sample.
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Michel J. Grothe, Miguel A. Labrador-Espinosa, Silvia Jesus, Daniel Macias-Garcia, Astrid Adarmes-Gomez, Fatima Carrillo, Elena Iglesias Camacho, Pablo Franco-Rosado, Florinda Roldan Lora, Juan Francisco Martin-Rodriguez, Miquel Aguilar Barbera, Pau Pastor, Sonia Escalante Arroyo, Berta Solano Vila, Anna Cots Foraster, Javier Ruiz Martinez, Francisco Carrillo Padilla, Mercedes Pueyo Morlans, Isabel Gonzalez Aramburu, Jon Infante Ceberio, Jorge Hernandez Vara, Oriol de Fabregues-Boixar, Teresa de Deus Fonticoba, Berta Pascual-Sedano, Jaime Kulisevsky, Pablo Martinez-Martin, Diego Santos-Garcia, Pablo Mir
Summary: Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Elisabetta Coppi, Federica Cherchi, Erica Sarchielli, Irene Fusco, Giulia Guarnieri, Pasquale Gallina, Renato Corradetti, Felicita Pedata, Gabriella B. Vannelli, Anna Maria Pugliese, Annamaria Morelli
Summary: This study characterized cholinergic effects in human NBM neurons, showing that acetylcholine can modulate ion channels by enhancing K currents, reducing Na currents, and activating different receptors. Spontaneous acetylcholine release from neuroblasts in the human fetal NBM may play a key role in brain development.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Neurosciences
Frances J. Northington, Panagiotis Kratimenos, Victoria Turnbill, Debra L. Flock, Daniella Asafu-Adjaye, Raul Chavez-Valdez, Lee J. Martin
Summary: Neonatal hypoxic-ischemic encephalopathy results in loss of choline acetyltransferase-positive neurons in the basal forebrain, correlated with hippocampal area loss. Abnormal ChAT+ neurons in the striatum and nbM are related to cortical and striatal area loss. Upregulation of cathepsin D+ particles is observed in the nbM, indicating cholinergic neuropathology may contribute to long-term dysfunction after neonatal brain injury.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Yuko Kondo-Takuma, Masayuki Mizuno, Yo Tsuda, Yuta Madokoro, Kengo Suzuki, Toyohiro Sato, Hiroshi Takase, Yuto Uchida, Ken-Ichi Adachi, Hideki Hida, Cesario Borlongan, Noriyuki Matsukawa
Summary: The cholinergic efferent network from the medial septal nucleus to the hippocampus is important for learning and memory processes. HCNP, a peptide involved in acetylcholine synthesis, plays a role in regulating acetylcholine release and incorporation into synaptic vesicles in the hippocampus. Knockout mice lacking HCNP-pp exhibited reduced acetylcholine release and levels of vesicular acetylcholine transporter in the hippocampus, indicating a potential role for HCNP in the cholinergic regulation of the septo-hippocampal network.
SCIENTIFIC REPORTS
(2021)
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
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
Biochemical Research Methods
Megan K. Gautier, Stephen D. Ginsberg
Summary: This study presents a method for quantifying immunolabeled early endosomes within basal forebrain cholinergic neurons using 3D reconstructed confocal z-stacks with Imaris software. Comparison of two image analysis programs, ImageJ and Imaris, revealed that Imaris provides superior accuracy and resolution in quantifying early endosomes. The method enables precise and direct quantification of all immunolabeled vesicles within a defined cell of interest.
JOURNAL OF NEUROSCIENCE METHODS
(2021)
Article
Multidisciplinary Sciences
Pasquale D'Acunzo, Rocio Perez-Gonzalez, Yohan Kim, Tal Hargash, Chelsea Miller, Melissa J. Alldred, Hediye Erdjument-Bromage, Sai C. Penikalapati, Monika Pawlik, Mitsuo Saito, Mariko Saito, Stephen D. Ginsberg, Thomas A. Neubert, Chris N. Goulbourne, Efrat Levy
Summary: The study identified a previously unknown population of double-membraned EVs called mitovesicles, which contain specific mitochondrial constituents and undergo changes during pathophysiological processes involving mitochondrial dysfunction. The development of a method for the selective isolation of mitovesicles opens up new possibilities for characterizing biological processes connecting EV biology and mitochondria dynamics in vivo, as well as for innovative therapeutic and diagnostic strategies.
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.
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)
Editorial Material
Geriatrics & Gerontology
Elliott J. Mufson, Stephen D. Ginsberg, Tao Ma, Aurelie Ledreux, Sylvia E. Perez
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Biology
Suhasini Joshi, Erica DaGama Gomes, Tai Wang, Adriana Corben, Tony Taldone, Srinivasa Gandu, Chao Xu, Sahil Sharma, Salma Buddaseth, Pengrong Yan, Lon Yin L. Chan, Askan Gokce, Vinagolu K. Rajasekhar, Lisa Shrestha, Palak Panchal, Justina Almodovar, Chander S. Digwal, Anna Rodina, Swathi Merugu, NagaVaraKishore Pillarsetty, Vlad Miclea, Radu I. Peter, Wanyan Wang, Stephen D. Ginsberg, Laura Tang, Marissa Mattar, Elisa de Stanchina, Kenneth H. Yu, Maeve Lowery, Olivera Grbovic-Huezo, Eileen M. O'Reilly, Yelena Janjigian, John H. Healey, William R. Jarnagin, Peter J. Allen, Chris Sander, Hediye Erdjument-Bromage, Thomas A. Neubert, Steven D. Leach, Gabriela Chiosis
Summary: By manipulating epichaperomes pharmacologically, the interactomes within tumors can be re-engineered for vulnerability and improved treatment efficacy, offering a paradigm to overcome drug resistance through pharmacologic manipulation of proteome-wide protein-protein interaction networks.
COMMUNICATIONS BIOLOGY
(2021)
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
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)
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)
Meeting Abstract
Cell & Tissue Engineering
M. N. Gordon, J. S. Beck, N. M. Kanaan, S. Kamath, K. Nash, S. D. Ginsberg, S. E. Counts
CELL TRANSPLANTATION
(2021)
