scholarly journals Sex Differences in the Cholinergic Basal Forebrain in the Ts65Dn Mouse Model of Down Syndrome and Alzheimer's Disease

2013 ◽  
Vol 24 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Christy M. Kelley ◽  
Brian E. Powers ◽  
Ramon Velazquez ◽  
Jessica A. Ash ◽  
Stephen D. Ginsberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Down Syndrome ◽  
Mouse Model ◽  
Basal Forebrain ◽  
Ts65dn Mouse ◽  
Cholinergic Basal Forebrain

Impaired Sustained Attention and Error-Induced Stereotypy in the Aged Ts65Dn Mouse: A Mouse Model of Down Syndrome and Alzheimer's Disease.

2004 ◽  
Vol 118 (6) ◽  
pp. 1196-1205 ◽  
Author(s):  
Lori L. Driscoll ◽  
Jenna C. Carroll ◽  
Jisook Moon ◽  
Linda S. Crnic ◽  
David A. Levitsky ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Mouse Model ◽  
Sustained Attention ◽  
Ts65dn Mouse

scholarly journals Oxidative Phosphorylation Is Dysregulated Within the Basocortical Circuit in a 6-month old Mouse Model of Down Syndrome and Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Melissa J. Alldred ◽  
Sang Han Lee ◽  
Grace E. Stutzmann ◽  
Stephen D. Ginsberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Mouse Model ◽  
Oxidative Phosphorylation ◽  
Basal Forebrain ◽  
Complex I ◽  
Neurological Dysfunction ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Oxidative Phosphorylation Pathway

Down syndrome (DS) is the primary genetic cause of intellectual disability (ID), which is due to the triplication of human chromosome 21 (HSA21). In addition to ID, HSA21 trisomy results in a number of neurological and physiological pathologies in individuals with DS, including progressive cognitive dysfunction and learning and memory deficits which worsen with age. Further exacerbating neurological dysfunction associated with DS is the concomitant basal forebrain cholinergic neuron (BFCN) degeneration and onset of Alzheimer’s disease (AD) pathology in early mid-life. Recent single population RNA sequencing (RNA-seq) analysis in the Ts65Dn mouse model of DS, specifically the medial septal cholinergic neurons of the basal forebrain (BF), revealed the mitochondrial oxidative phosphorylation pathway was significantly impacted, with a large subset of genes within this pathway being downregulated. We further queried oxidative phosphorylation pathway dysregulation in Ts65Dn mice by examining genes and encoded proteins within brain regions comprising the basocortical system at the start of BFCN degeneration (6 months of age). In select Ts65Dn mice we demonstrate significant deficits in gene and/or encoded protein levels of Complex I-V of the mitochondrial oxidative phosphorylation pathway in the BF. In the frontal cortex (Fr Ctx) these complexes had concomitant alterations in select gene expression but not of the proteins queried from Complex I-V, suggesting that defects at this time point in the BF are more severe and occur prior to cortical dysfunction within the basocortical circuit. We propose dysregulation within mitochondrial oxidative phosphorylation complexes is an early marker of cognitive decline onset and specifically linked to BFCN degeneration that may propagate pathology throughout cortical memory and executive function circuits in DS and AD.

Sex differences in response to a high fat diet in an Alzheimer’s Disease mouse model

2018 ◽  
Author(s):  
Alejandra Freire Fernández-Regatillo ◽  
María L. de Ceballos ◽  
Jesús Argente ◽  
Sonia Díaz Pacheco ◽  
Clara González Martínez
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Mouse Model ◽  
High Fat Diet ◽  
High Fat

scholarly journals Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Jose L. Martinez ◽  
Matthew D. Zammit ◽  
Nicole R. West ◽  
Bradley T. Christian ◽  
Anita Bhattacharyya
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Basal Forebrain ◽  
Critical Role ◽  
Memory Loss ◽  
Cholinergic Neurons ◽  
Cholinergic Innervation ◽  
Attention And Memory ◽  
Basal Forebrain Cholinergic Neurons

Down syndrome (DS, trisomy 21) is characterized by intellectual impairment at birth and Alzheimer’s disease (AD) pathology in middle age. As individuals with DS age, their cognitive functions decline as they develop AD pathology. The susceptibility to degeneration of a subset of neurons, known as basal forebrain cholinergic neurons (BFCNs), in DS and AD is a critical link between cognitive impairment and neurodegeneration in both disorders. BFCNs are the primary source of cholinergic innervation to the cerebral cortex and hippocampus, as well as the amygdala. They play a critical role in the processing of information related to cognitive function and are directly engaged in regulating circuits of attention and memory throughout the lifespan. Given the importance of BFCNs in attention and memory, it is not surprising that these neurons contribute to dysfunctional neuronal circuitry in DS and are vulnerable in adults with DS and AD, where their degeneration leads to memory loss and disturbance in language. BFCNs are thus a relevant cell target for therapeutics for both DS and AD but, despite some success, efforts in this area have waned. There are gaps in our knowledge of BFCN vulnerability that preclude our ability to effectively design interventions. Here, we review the role of BFCN function and degeneration in AD and DS and identify under-studied aspects of BFCN biology. The current gaps in BFCN relevant imaging studies, therapeutics, and human models limit our insight into the mechanistic vulnerability of BFCNs in individuals with DS and AD.

Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer’s Disease

2020 ◽  
Author(s):  
Melissa J. Alldred ◽  
Sai C. Penikalapati ◽  
Sang Han Lee ◽  
Adriana Heguy ◽  
Panos Roussos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Basal Forebrain ◽  
Differentially Expressed Gene ◽  
Cholinergic Neurons ◽  
Bioinformatic Analysis ◽  
Selective Vulnerability ◽  
Neuronal Population ◽  
Single Population

Abstract Background: Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer’s disease (AD). Current therapeutics have been unsuccessful in slowing disease progression, likely due to complex pathological interactions and dysregulated pathways that are poorly understood. The Ts65Dn trisomic mouse model recapitulates both cognitive and morphological deficits of DS and AD, including BFCN degeneration. Methods: We utilized Ts65Dn mice to understand mechanisms underlying BFCN degeneration to identify novel targets for therapeutic intervention. We performed high-throughput, single population RNA sequencing (RNA-seq) to interrogate transcriptomic changes within medial septal nucleus (MSN) BFCNs, using laser capture microdissection to individually isolate ~500 choline acetyltransferase-immunopositive neurons in Ts65Dn and normal disomic (2N) mice at 6 months of age (MO). Results: Ts65Dn mice had unique MSN BFCNs transcriptomic profiles at ~6 MO clearly differentiating them from 2N mice. Leveraging Ingenuity Pathway Analysis and KEGG analysis, we linked differentially expressed gene (DEG) changes within MSN BFCNs to several canonical pathways and aberrant physiological functions. The dysregulated transcriptomic profile of trisomic BFCNs provides key information underscoring selective vulnerability within the septohippocampal circuit. Conclusions: We propose both expected and novel therapeutic targets for DS and AD, including specific DEGs within cholinergic, glutamate, GABAergic, and neurotrophin pathways, as well as select targets for repairing oxidative phosphorylation status in neurons. We demonstrate and validate an interrogative quantitative bioinformatic analysis of a key dysregulated neuronal population linking single population transcript changes to an established pathological hallmark associated with cognitive decline for therapeutic development in human DS and AD.

scholarly journals The role of calbindin‐D28k in a mouse model of Down syndrome‐related Alzheimer's disease

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Eric D. Hamlett ◽  
Steven L. Carroll ◽  
Ann‐Charlotte Granholm
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Mouse Model ◽  
Calbindin D28k

scholarly journals Sex Differences in Healthspan Predict Lifespan in the 3xTg-AD Mouse Model of Alzheimer’s Disease

2018 ◽  
Vol 10 ◽  
Author(s):  
Alice E. Kane ◽  
Sooyoun Shin ◽  
Aimee A. Wong ◽  
Emre Fertan ◽  
Natalia S. Faustova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
Ad Mouse Model
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