Cholinergic neuron gene expression differences captured by translational profiling in a mouse model of Alzheimer's disease. 2017

Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.

Cholinergic neurotransmission is impaired in Alzheimer's disease (AD), and loss of basal forebrain cholinergic neurons is a key component of disease pathogenicity and symptomatology. To explore the molecular basis of this cholinergic dysfunction, we paired translating ribosome affinity purification (TRAP) with RNA sequencing (TRAP-Seq) to identify the actively translating mRNAs in anterior forebrain cholinergic neurons in the TgCRND8 mouse model of AD. Bioinformatic analyses revealed the downregulation of 67 of 71 known cholinergic-related transcripts, consistent with cholinergic neuron dysfunction in TgCRND8 mice, as well as transcripts related to oxidative phosphorylation, neurotrophins, and ribosomal processing. Upregulated transcripts included those related to axon guidance, glutamatergic synapses and kinase activity and included AD-risk genes Sorl1 and Ptk2b. In contrast, the total transcriptome of the anterior forebrain showed upregulation in cytokine signaling, microglia, and immune system pathways, including Trem2, Tyrobp, and Inpp5d. Hence, TRAP-Seq clearly distinguished the differential gene expression alterations occurring in cholinergic neurons of TgCRND8 mice compared with wild-type littermates, providing novel candidate pathways to explore for therapeutic development in AD.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009414 Nerve Growth Factors Factors which enhance the growth potentialities of sensory and sympathetic nerve cells. Neurite Outgrowth Factor,Neurite Outgrowth Factors,Neuronal Growth-Associated Protein,Neuronotrophic Factor,Neurotrophic Factor,Neurotrophic Factors,Neurotrophin,Neurotrophins,Growth-Associated Proteins, Neuronal,Neuronal Growth-Associated Proteins,Neuronotrophic Factors,Neurotrophic Protein,Neurotrophic Proteins,Proteins, Neuronal Growth-Associated,Factor, Neurite Outgrowth,Factor, Neuronotrophic,Factor, Neurotrophic,Factors, Nerve Growth,Factors, Neurite Outgrowth,Factors, Neuronotrophic,Factors, Neurotrophic,Growth Associated Proteins, Neuronal,Growth-Associated Protein, Neuronal,Neuronal Growth Associated Protein,Neuronal Growth Associated Proteins,Outgrowth Factor, Neurite,Outgrowth Factors, Neurite,Protein, Neuronal Growth-Associated
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011973 Receptors, LDL Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking. LDL Receptors,Lipoprotein LDL Receptors,Receptors, Low Density Lipoprotein,LDL Receptor,LDL Receptors, Lipoprotein,Low Density Lipoprotein Receptor,Low Density Lipoprotein Receptors,Receptors, Lipoprotein, LDL,Receptor, LDL,Receptors, Lipoprotein LDL
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000071437 Axon Guidance The mechanism by which a neuronal process outgrows toward a target led by the GROWTH CONE. Local guidance cues are provided by cell surface proteins that act on the growing axon. Axon Pathfinding,Axonal Pathfinding,Neural Guidance,Neural Pathfinding,Neurite Guidance,Neuronal Guidance,Neuronal Pathfinding,Pathfinding, Axon
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
January 2016, Journal of Alzheimer's disease : JAD,
Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
August 2003, The Journal of comparative neurology,
Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
January 2019, Journal of Alzheimer's disease : JAD,
Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
January 2018, Journal of Alzheimer's disease : JAD,
Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
January 2017, Current Alzheimer research,
Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
July 2010, Neurobiology of aging,
Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
July 2006, NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics,
Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
January 2012, Journal of Alzheimer's disease : JAD,
Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
December 2022, Cell insight,
Paul M McKeever, and TaeHyung Kim, and Andrew R Hesketh, and Laura MacNair, and Denise Miletic, and Giorgio Favrin, and Stephen G Oliver, and Zhaolei Zhang, and Peter St George-Hyslop, and Janice Robertson
January 2017, BioMed research international,
Copied contents to your clipboard!