Article
Neurosciences
Fulton T. Crews, Ryan P. Vetreno
Summary: Inflammatory signaling through HMGB1-TLR4 in BFCNs leads to reversible loss of the cholinergic neuron phenotype via epigenetic gene repression mechanisms. Inhibiting TLR4 can prevent or reverse the loss of ChAT + IR neurons induced by LPS, while inhibition of HMGB1 can also mitigate this effect.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Behavioral Sciences
Linghong Chen, Yuting Ke, Hong Ma, Lei Gao, Yiying Zhou, Huaqiang Zhu, Huifen Liu, Fuqiang Zhang, Wenhua Zhou
Summary: The study revealed that a lesion of HDB cholinergic neurons in rats led to depressive and anxiety-like behaviors. Antidepressants such as fluoxetine or ketamine could reverse depressive-like behaviors but not anxiety-like behaviors.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Jiaojiao Tian, Miao Ren, Peilin Zhao, Shukang Luo, Yingying Chen, Xiaofeng Xu, Tao Jiang, Qingtao Sun, Anan Li, Hui Gong, Xiangning Li, Qingming Luo
Summary: Through synaptic connections, the brain forms functional motifs and executes specific functions. Researchers successfully mapped the whole-brain distribution and architecture of long projections of specific neurons, and found that synaptic degeneration was inconsistent with the accumulation of amyloid-beta plaques but was preferred in memory-related circuits.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Ping Zhong, Qing Cao, Zhen Yan
Summary: Alzheimer's disease is a neurodegenerative disorder associated with cognitive decline. The study reveals that there are functional changes in the neural circuits between the prefrontal cortex and basal forebrain in a tauopathy mouse model, which may contribute to the loss of attention and executive function.
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
Clinical Neurology
Julia Schumacher, Prabesh Kanel, Martin Dyrba, Alexander Storch, Nicolaas Bohnen, Stefan Teipel, Michel J. Grothe
Summary: The study aimed to investigate the relationship between basal forebrain degeneration and cortical acetylcholinesterase activity in Parkinson’s disease, as well as their contribution to cognitive impairment. The findings demonstrated that the hypo-cholinergic Parkinson’s group had significantly reduced posterior basal forebrain volume compared to both the normo-cholinergic Parkinson’s group and the control group. Furthermore, the volume of posterior basal forebrain was significantly associated with cortical acetylcholinesterase activity in Parkinson’s patients, and both cholinergic markers were independently associated with multi-domain cognitive deficits.
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
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
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
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
Neurosciences
Megan K. Gautier, Christy M. Kelley, Sang Han Lee, Melissa J. Alldred, John Mcdaid, Elliott J. Mufson, Grace E. Stutzmann, Stephen D. Ginsberg
Summary: Down syndrome (DS), a genetic disorder, affects brain development and cognitive abilities. Maternal choline supplementation shows potential for protecting vulnerable neurons and improving cognitive function.
NEUROBIOLOGY OF DISEASE
(2023)
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
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
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
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
Melissa J. Alldred, Sai C. Penikalapati, Sang Han Lee, Adriana Heguy, Panos Roussos, Stephen D. Ginsberg
Summary: The basal forebrain cholinergic neuron degeneration is a common feature in Down syndrome and Alzheimer's disease. Utilizing the Ts65Dn trisomic mouse model, researchers identified novel therapeutic targets by analyzing transcriptomic profiles of medial septal nucleus BFCNs. The dysregulated transcriptomic profile of trisomic BFCNs provides key information on selective vulnerability within the septohippocampal circuit, offering potential insights for therapeutic approaches in DS and AD.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Alexander Bolaender, Danuta Zatorska, Huazhong He, Suhasini Joshi, Sahil Sharma, Chander S. Digwal, Hardik J. Patel, Weilin Sun, Brandon S. Imber, Stefan O. Ochiana, Maulik R. Patel, Liza Shrestha, Smit. K. Shah, Shuo Wang, Rashad Karimov, Hui Tao, Pallav D. Patel, Ananda Rodilla Martin, Pengrong Yan, Palak Panchal, Justina Almodovar, Adriana Corben, Andreas Rimner, Stephen D. Ginsberg, Serge Lyashchenko, Eva Burnazi, Anson Ku, Teja Kalidindi, Sang Gyu Lee, Milan Grkovski, Bradley J. Beattie, Pat Zanzonico, Jason S. Lewis, Steve Larson, Anna Rodina, Nagavarakishore Pillarsetty, Viviane Tabar, Mark P. Dunphy, Tony Taldone, Fumiko Shimizu, Gabriela Chiosis
Summary: This study investigates the use of epichaperome-directed chemical probes for detecting and reversing defective chaperomes in diseases, particularly focusing on their application in central nervous system disorders. The results demonstrate the on-target activity and kinetic selectivity of the probes in cells, mice, and human patients in a clinical trial, showing potential for modulating epichaperomes in complex biological systems.
NATURE COMMUNICATIONS
(2021)
Article
Geriatrics & Gerontology
Melissa J. Alldred, Sang Han Lee, Grace E. Stutzmann, Stephen D. Ginsberg
Summary: Down syndrome (DS) is caused by the triplication of human chromosome 21 and leads to intellectual disability as well as a number of neurological and physiological pathologies. Recent RNA sequencing analysis in a DS mouse model showed significant impact on the mitochondrial oxidative phosphorylation pathway. Deficits in this pathway may serve as an early marker of cognitive decline onset and are specifically linked to basocortical system dysfunction.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Medicine, General & Internal
Melissa J. Alldred, Sang Han Lee, Stephen D. Ginsberg
Summary: Down syndrome is a genetic disorder caused by the triplication of chromosome 21, leading to neurological and physiological pathologies which worsen with age. Maternal choline supplementation may attenuate cognitive decline in DS and AD mouse models. The dysregulation of adiponectin (APN) in the brain could be an early marker of cognitive decline and neurodegeneration, suggesting its potential as a biomarker for AD pathology.
JOURNAL OF CLINICAL MEDICINE
(2021)
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
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)
