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Start Over Descriptor "BFCN" Topic alzheimer disease
3 results on '"BFCN"'

1. CRISPR/Cas9-Correctable mutation-related molecular and physiological phenotypes in iPSC-derived Alzheimer's PSEN2 N141I neurons.

Author

Ortiz-Virumbrales M, Moreno CL, Kruglikov I, Marazuela P, Sproul A, Jacob S, Zimmer M, Paull D, Zhang B, Schadt EE, Ehrlich ME, Tanzi RE, Arancio O, Noggle S, and Gandy S

Subjects
Action Potentials, Adaptor Proteins, Signal Transducing metabolism, Adult, Alzheimer Disease genetics, Alzheimer Disease pathology, Alzheimer Disease therapy, Amyloid beta-Peptides metabolism, Apoptosis Regulatory Proteins, Basal Forebrain metabolism, Cell Death, Cell Line, Cholinergic Neurons pathology, Female, Heterozygote, Humans, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells metabolism, Male, Mutation, Neural Stem Cells cytology, Neural Stem Cells metabolism, Neural Stem Cells pathology, Neurogenesis, Peptide Fragments metabolism, Presenilin-2 metabolism, RNA, Messenger metabolism, Alzheimer Disease physiopathology, CRISPR-Cas Systems, Cholinergic Neurons physiology, Gene Editing, Induced Pluripotent Stem Cells physiology, Presenilin-2 genetics
Abstract

Basal forebrain cholinergic neurons (BFCNs) are believed to be one of the first cell types to be affected in all forms of AD, and their dysfunction is clinically correlated with impaired short-term memory formation and retrieval. We present an optimized in vitro protocol to generate human BFCNs from iPSCs, using cell lines from presenilin 2 (PSEN2) mutation carriers and controls. As expected, cell lines harboring the PSEN2 N141I mutation displayed an increase in the Aβ42/40 in iPSC-derived BFCNs. Neurons derived from PSEN2 N141I lines generated fewer maximum number of spikes in response to a square depolarizing current injection. The height of the first action potential at rheobase current injection was also significantly decreased in PSEN2 N141I BFCNs. CRISPR/Cas9 correction of the PSEN2 point mutation abolished the electrophysiological deficit, restoring both the maximal number of spikes and spike height to the levels recorded in controls. Increased Aβ42/40 was also normalized following CRISPR/Cas-mediated correction of the PSEN2 N141I mutation. The genome editing data confirms the robust consistency of mutation-related changes in Aβ42/40 ratio while also showing a PSEN2-mutation-related alteration in electrophysiology.

Published
2017
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2. Stimulate or degenerate: deep brain stimulation of the nucleus basalis Meynert in Alzheimer dementia.

Author

Hardenacke K, Kuhn J, Lenartz D, Maarouf M, Mai JK, Bartsch C, Freund HJ, and Sturm V

Subjects
Aged, Aged, 80 and over, Alzheimer Disease physiopathology, Alzheimer Disease psychology, Basal Nucleus of Meynert pathology, Cognition physiology, Humans, Neurodegenerative Diseases pathology, Prosencephalon pathology, Prosencephalon physiology, Alzheimer Disease surgery, Basal Nucleus of Meynert physiology, Deep Brain Stimulation methods
Abstract

Objective: Deep brain stimulation (DBS) is a therapeutically effective neurosurgical method originally applied in movement disorders. Over time, the application of DBS has increasingly been considered as a therapeutic option for several neuropsychiatric disorders, including Gilles de la Tourette syndrome, obsessive compulsive disorder, major depression and addiction. Latest research suggests beneficial effects of DBS in Alzheimer dementia (AD). Because of the high prevalence and the considerable burden of the disease, we endeavored to discuss and reveal the challenges of DBS in AD., Methods: Recent literature on the pathophysiology of AD, including translational data and human studies, has been studied to generate a fundamental hypothesis regarding the effects of electrical stimulation on cognition and to facilitate our ongoing pilot study regarding DBS of the nucleus basalis Meynert (NBM) in patients with AD., Results: It is hypothesized that DBS in the nucleus basalis Meynert could probably improve or at least stabilize memory and cognitive functioning in patients with AD by facilitating neural oscillations and by enhancing the synthesis of nerve growth factors., Conclusions: Considering the large number of patients suffering from AD, there is a great need for novel and effective treatment methods. Our research provides insights into the theoretical background of DBS in AD. Providing that our hypothesis will be validated by our ongoing pilot study, DBS could be an opportunity in the treatment of AD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Published
2013
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3. CRISPR/Cas9-Correctable mutation-related molecular and physiological phenotypes in iPSC-derived Alzheimer’s PSEN2N141I neurons

Author

Maitane Ortiz-Virumbrales, Samson T. Jacob, Michelle E. Ehrlich, Scott Noggle, Cesar L. Moreno, Andrew Sproul, Matthew Zimmer, Ottavio Arancio, I. A. Kruglikov, Paula Marazuela, Eric E. Schadt, Daniel Paull, Bin Zhang, Sam Gandy, and Rudolph E. Tanzi

Subjects
0301 basic medicine, Male, Action Potentials, BFCN, lcsh:RC346-429, 0302 clinical medicine, Neural Stem Cells, CRISPR, Cholinergic, Gene Editing, PSEN2, iPSC, Cell Death, Cholinergic Neurons, Electrophysiology, Rheobase, Mutation (genetic algorithm), Female, Alzheimer’s disease, Adult, Heterozygote, Basal Forebrain, Neurogenesis, Induced Pluripotent Stem Cells, Biology, Presenilin, Pathology and Forensic Medicine, Cell Line, Basal forebrain, 03 medical and health sciences, Cellular and Molecular Neuroscience, Alzheimer Disease, Presenilin-2, Humans, RNA, Messenger, Cholinergic neuron, CRISPR/Cas9, lcsh:Neurology. Diseases of the nervous system, Adaptor Proteins, Signal Transducing, Amyloid beta-Peptides, Point mutation, Research, Peptide Fragments, 030104 developmental biology, Mutation, Neurology (clinical), CRISPR-Cas Systems, Apoptosis Regulatory Proteins, Neuroscience, 030217 neurology & neurosurgery
Abstract

Basal forebrain cholinergic neurons (BFCNs) are believed to be one of the first cell types to be affected in all forms of AD, and their dysfunction is clinically correlated with impaired short-term memory formation and retrieval. We present an optimized in vitro protocol to generate human BFCNs from iPSCs, using cell lines from presenilin 2 (PSEN2) mutation carriers and controls. As expected, cell lines harboring the PSEN2 N141I mutation displayed an increase in the Aβ42/40 in iPSC-derived BFCNs. Neurons derived from PSEN2 N141I lines generated fewer maximum number of spikes in response to a square depolarizing current injection. The height of the first action potential at rheobase current injection was also significantly decreased in PSEN2 N141I BFCNs. CRISPR/Cas9 correction of the PSEN2 point mutation abolished the electrophysiological deficit, restoring both the maximal number of spikes and spike height to the levels recorded in controls. Increased Aβ42/40 was also normalized following CRISPR/Cas-mediated correction of the PSEN2 N141I mutation. The genome editing data confirms the robust consistency of mutation-related changes in Aβ42/40 ratio while also showing a PSEN2-mutation-related alteration in electrophysiology.

Published
2017

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