scholarly journals Blood lactate dynamics in awake and anaesthetized mice after intraperitoneal and subcutaneous injections of lactate—sex matters

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8328
Author(s):  
Øyvind P. Haugen ◽  
Evan M. Vallenari ◽  
Imen Belhaj ◽  
Milada Cvancarova Småstuen ◽  
Jon Storm-Mathisen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Lactate ◽  
Mouse Models ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
High Intensity Training ◽  
Significant Difference ◽  
5Xfad Mouse ◽  
Lactate Levels

Lactate treatment has shown a therapeutic potential for several neurological diseases, including Alzheimer’s disease. In order to optimize the administration of lactate for studies in mouse models, we compared blood lactate dynamics after intraperitoneal (IP) and subcutaneous (SC) injections. We used the 5xFAD mouse model for familial Alzheimer’s disease and performed the experiments in both awake and anaesthetized mice. Blood glucose was used as an indication of the hepatic conversion of lactate. In awake mice, both injection routes resulted in high blood lactate levels, mimicking levels reached during high-intensity training. In anaesthetized mice, SC injections resulted in significantly lower lactate levels compared to IP injections. Interestingly, we observed that awake males had significantly higher lactate levels than awake females, while the opposite sex difference was observed during anaesthesia. We did not find any significant difference between transgenic and wild-type mice and therefore believe that our results can be generalized to other mouse models. These results should be considered when planning experiments using lactate treatment in mice.

scholarly journals Dynamics of Dynamin-Related Protein 1 in Alzheimer’s Disease and Other Neurodegenerative Diseases

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 961 ◽  
Author(s):  
Darryll Oliver ◽  
P. Reddy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Mouse Models ◽  
Cell Cultures ◽  
Neuronal Damage ◽  
Mitochondrial Dynamics ◽  
Neurological Diseases ◽  
Large Family ◽  
Related Protein

The purpose of this article is to highlight the role of dynamin-related protein 1 (Drp1) in abnormal mitochondrial dynamics, mitochondrial fragmentation, autophagy/mitophagy, and neuronal damage in Alzheimer’s disease (AD) and other neurological diseases, including Parkinson’s, Huntington’s, amyotrophic lateral sclerosis, multiple sclerosis, diabetes, and obesity. Dynamin-related protein 1 is one of the evolutionarily highly conserved large family of GTPase proteins. Drp1 is critical for mitochondrial division, size, shape, and distribution throughout the neuron, from cell body to axons, dendrites, and nerve terminals. Several decades of intense research from several groups revealed that Drp1 is enriched at neuronal terminals and involved in synapse formation and synaptic sprouting. Different phosphorylated forms of Drp1 acts as both increased fragmentation and/or increased fusion of mitochondria. Increased levels of Drp1 were found in diseased states and caused excessive fragmentation of mitochondria, leading to mitochondrial dysfunction and neuronal damage. In the last two decades, several Drp1 inhibitors have been developed, including Mdivi-1, Dynasore, P110, and DDQ and their beneficial effects tested using cell cultures and mouse models of neurodegenerative diseases. Recent research using genetic crossing studies revealed that a partial reduction of Drp1 is protective against mutant protein(s)-induced mitochondrial and synaptic toxicities. Based on findings from cell cultures, mouse models and postmortem brains of AD and other neurodegenerative disease, we cautiously conclude that reduced Drp1 is a promising therapeutic target for AD and other neurological diseases.

scholarly journals Does Chronic Sleep Fragmentation Lead to Alzheimer's Disease in Young Wild-Type Mice?

2021 ◽  
Vol 13 ◽  
Author(s):  
Li Ba ◽  
Lifang Huang ◽  
Ziyu He ◽  
Saiyue Deng ◽  
Yi Xie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Metabolism ◽  
Differential Expression ◽  
Mouse Models ◽  
Neurological Diseases ◽  
Expression Patterns ◽  
Sleep Fragmentation ◽  
Wild Type ◽  
Chronic Sleep

Chronic sleep insufficiency is becoming a common issue in the young population nowadays, mostly due to life habits and work stress. Studies in animal models of neurological diseases reported that it would accelerate neurodegeneration progression and exacerbate interstitial metabolic waste accumulation in the brain. In this paper, we study whether chronic sleep insufficiency leads to neurodegenerative diseases in young wild-type animals without a genetic pre-disposition. To this aim, we modeled chronic sleep fragmentation (SF) in young wild-type mice. We detected pathological hyperphosphorylated-tau (Ser396/Tau5) and gliosis in the SF hippocampus. 18F-labeled fluorodeoxyglucose positron emission tomography scan (18F-FDG-PET) further revealed a significant increase in brain glucose metabolism, especially in the hypothalamus, hippocampus and amygdala. Hippocampal RNAseq indicated that immunological and inflammatory pathways were significantly altered in 1.5-month SF mice. More interestingly, differential expression gene lists from stress mouse models showed differential expression patterns between 1.5-month SF and control mice, while Alzheimer's disease, normal aging, and APOEε4 mutation mouse models did not exhibit any significant pattern. In summary, 1.5-month sleep fragmentation could generate AD-like pathological changes including tauopathy and gliosis, mainly linked to stress, as the incremented glucose metabolism observed with PET imaging suggested. Further investigation will show whether SF could eventually lead to chronic neurodegeneration if the stress condition is prolonged in time.

scholarly journals A novel systems biology approach to evaluate mouse models of late-onset Alzheimer’s disease

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Christoph Preuss ◽  
◽  
Ravi Pandey ◽  
Erin Piazza ◽  
Alexander Fine ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Mouse Models ◽  
Late Onset ◽  
Cost Effective ◽  
Common Disease ◽  
Disease Genes ◽  
Postmortem Human Brain ◽  
5Xfad Mouse

Abstract Background Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia worldwide. To date, animal models of Alzheimer’s have focused on rare familial mutations, due to a lack of frank neuropathology from models based on common disease genes. Recent multi-cohort studies of postmortem human brain transcriptomes have identified a set of 30 gene co-expression modules associated with LOAD, providing a molecular catalog of relevant endophenotypes. Results This resource enables precise gene-based alignment between new animal models and human molecular signatures of disease. Here, we describe a new resource to efficiently screen mouse models for LOAD relevance. A new NanoString nCounter® Mouse AD panel was designed to correlate key human disease processes and pathways with mRNA from mouse brains. Analysis of the 5xFAD mouse, a widely used amyloid pathology model, and three mouse models based on LOAD genetics carrying APOE4 and TREM2*R47H alleles demonstrated overlaps with distinct human AD modules that, in turn, were functionally enriched in key disease-associated pathways. Comprehensive comparison with full transcriptome data from same-sample RNA-Seq showed strong correlation between gene expression changes independent of experimental platform. Conclusions Taken together, we show that the nCounter Mouse AD panel offers a rapid, cost-effective and highly reproducible approach to assess disease relevance of potential LOAD mouse models.

P3-296: Characterization of Vascular Alterations in Human Alzheimer's Disease Patients in Comparison to the AppSL and 5XFAD Mouse Models

2016 ◽  
Vol 12 ◽  
pp. P954-P954
Author(s):  
Vera Niederkofler ◽  
Magdalena Temmel ◽  
Karin Lanegger ◽  
Joerg Neddens ◽  
Ewald Auer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
5Xfad Mouse

Bexarotene cannot reduce amyloid beta plaques through inhibition of production of amyloid beta peptides:in silicoandin vitrostudy

2018 ◽  
Vol 20 (37) ◽  
pp. 24329-24338 ◽  
Author(s):  
Huy Dinh Quoc Pham ◽  
Nguyen Quoc Thai ◽  
Zuzana Bednarikova ◽  
Huynh Quang Linh ◽  
Zuzana Gazova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Amyloid Beta ◽  
Therapeutic Potential ◽  
Cancer Drug ◽  
Anti Cancer

Recently, it has been reported that anti-cancer drug bexarotene can remarkably destroy amyloid beta (Aβ) plaques in mouse models suggesting therapeutic potential for Alzheimer's disease.

scholarly journals Mutual Interactions between Brain States and Alzheimer’s Disease Pathology: A Focus on Gamma and Slow Oscillations

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 707
Author(s):  
Nicole Byron ◽  
Anna Semenova ◽  
Shuzo Sakata
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Therapeutic Potential ◽  
Brain Diseases ◽  
Pharmacological Intervention ◽  
Brain State ◽  
Population Activity ◽  
Slow Oscillations ◽  
Brain States

Brain state varies from moment to moment. While brain state can be defined by ongoing neuronal population activity, such as neuronal oscillations, this is tightly coupled with certain behavioural or vigilant states. In recent decades, abnormalities in brain state have been recognised as biomarkers of various brain diseases and disorders. Intriguingly, accumulating evidence also demonstrates mutual interactions between brain states and disease pathologies: while abnormalities in brain state arise during disease progression, manipulations of brain state can modify disease pathology, suggesting a therapeutic potential. In this review, by focusing on Alzheimer’s disease (AD), the most common form of dementia, we provide an overview of how brain states change in AD patients and mouse models, and how controlling brain states can modify AD pathology. Specifically, we summarise the relationship between AD and changes in gamma and slow oscillations. As pathological changes in these oscillations correlate with AD pathology, manipulations of either gamma or slow oscillations can modify AD pathology in mouse models. We argue that neuromodulation approaches to target brain states are a promising non-pharmacological intervention for neurodegenerative diseases.

scholarly journals Sex and Genotype Differences in Odor Detection in the 3×Tg-AD and 5XFAD Mouse Models of Alzheimer’s Disease at 6 Months of Age

2016 ◽  
Vol 41 (5) ◽  
pp. 433-440 ◽  
Author(s):  
Kyle M. Roddick ◽  
Amelia D. Roberts ◽  
Heather M. Schellinck ◽  
Richard E. Brown
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Odor Detection ◽  
5Xfad Mouse

scholarly journals Agmatine: A potential Neurotherapeutic Agent

2021 ◽  
Vol 11 (4) ◽  
pp. 88-92
Author(s):  
Neha Binjhade ◽  
Vinanti Supare ◽  
Shailesh Ghaywat ◽  
Sagar Trivedi ◽  
Kamlesh Wadher ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Neuroprotective Effect ◽  
Cognitive Disorders ◽  
Polyamine Metabolism ◽  
Trauma Brain Injury

Agmatine, a natural polyamine disregarded almost for over 100 years, was discovered in year 1910. Almost after a decade, several researches on Agmatine indicated its modulatory action at multiple molecular targets such as, nitric oxide synthesis, neurotransmitter systems, and polyamine metabolism unbolt the new avenues for extensive therapeutic applications which includes neurotrauma and neurodegenerative diseases, antidepressant, cognitive disorders. Agmatine exerts its varied biological characteristics and therapeutic potential in diverse arena. Agmatine has been extensively researched for its neuroprotective effect in various types of neurological diseases, including stroke and trauma brain injury along with Parkinson's disease, Alzheimer's disease, Hypoxia /Ischemia. In the present review we have summarized the therapeutic potential of agmatine as protective and regenerative properties in the CNS. Keywords: Agmatine, Neuroprotective, Alzheimer's disease, Parkinson's disease, CNS disorders.

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