scholarly journals Alterations in tanycytes and related cell populations of arcuate nucleus in streptozotocin-induced Alzheimer disease model

2021 ◽  
Author(s):  
DN Voronkov ◽  
AV Stavrovskaya ◽  
AS Gushchina ◽  
AS Olshansky
Keyword(s):  
Alzheimer Disease ◽  
Arcuate Nucleus ◽  
Disease Model ◽  
Protein Markers ◽  
Complex Iv ◽  
Mitochondrial Alterations ◽  
Amyloid Accumulation ◽  
Β Amyloid

It is assumed that dysfunction of tanycytes could be one of the components of pathogenesis of both Alzheimer disease and type 2 diabetes mellitus. The study was aimed to assess alterations in the tanycyte morphology in the Alzheimer disease model. The 3 mg/kg streptozotocin dose was injected in the lateral ventricles of Wistar rats in order to model the Alzheimer disease. Alterations in hypothalamic tanycytes were assessed 2 weeks, 4 weeks, 3 months and 6 months after administration of the toxin. Immunohistochemistry was used to identify the protein markers of tanycytes (vimentin, nestin), astrocytes (GFAP, glutamine synthetase) and neurons (HuC/D), as well as to assess cell proliferation (with the use of Ki67 protein) and mitochondrial alterations (mitochondrial complex IV, PGC1a). Administration of streptozotocin lead to β-amyloid accumulation in hypothalamus and ventricular enlargement (p < 0.001). Streptozotocin damaged both α1/α2 tanycytes and β1 tanycytes. The intensity of vimentin staining in α1/α2 tanycytes decreased by week 4 (p = 0.003), and in β1 tanycytes it decreased in three months (p < 0.001). The same trend was observed for nestin. The number of Ki67+ nuclei decreased (p < 0.05), and the expression of proteins associated with mitochondria changed. The density of hypothalamic tanycytes decreased by week 4 after administration of the toxin. Moreover, astrocyte activation was revealed. However, no prominent damage to both astrocytes and neurons was observed within four weeks after administration of streptozotocin. The revealed high tanycyte vulnerability to streptozotocin is in line with the hypothesis of the role of damage to hypothalamic structures in both local and systemic metabolic disorders occurring in the Alzheimer disease models.

scholarly journals Microglia in Alzheimer’s Disease: A Target for Therapeutic Intervention

2021 ◽  
Vol 15 ◽  
Author(s):  
Guimei Zhang ◽  
Zicheng Wang ◽  
Huiling Hu ◽  
Meng Zhao ◽  
Li Sun
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Interventions ◽  
Tau Pathology ◽  
Age Related ◽  
Amyloid Accumulation ◽  
Pathophysiological Role ◽  
Inflammatory Drugs ◽  
Β Amyloid

Alzheimer’s disease (AD) is one of the most common types of age-related dementia worldwide. In addition to extracellular amyloid plaques and intracellular neurofibrillary tangles, dysregulated microglia also play deleterious roles in the AD pathogenesis. Numerous studies have demonstrated that unbridled microglial activity induces a chronic neuroinflammatory environment, promotes β-amyloid accumulation and tau pathology, and impairs microglia-associated mitophagy. Thus, targeting microglia may pave the way for new therapeutic interventions. This review provides a thorough overview of the pathophysiological role of the microglia in AD and illustrates the potential avenues for microglia-targeted therapies, including microglial modification, immunoreceptors, and anti-inflammatory drugs.

scholarly journals ROLE OF INSULIN IN BRAIN: DELVE INTO THE MOLECULAR MECHANISMS

2021 ◽  
Author(s):  
Sofia Khanam
Keyword(s):  
Molecular Mechanisms ◽  
Insulin Signalling ◽  
Diabetic Patients ◽  
Functional Activities ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
The Brain ◽  
And Oxidative Stress

We have learned over the last several decades that the brain is an important target for insulin action. In central nervous system (CNS) it mainly affects feeding behaviour and various aspects of memory and cognition. Insulin signalling in CNS has emerged as a novel field of research since decreases brain insulin levels and signalling were associated to impaired learning, memory and age-related neurodegenerative diseases. Alterations of these functional activities may contribute to the manifestation of several clinical entities, such as central insulin resistance, type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). A close alliance between T2DM and AD has been reported, to the extent that AD is twice more frequent in diabetic patients. There are links between T2DM and AD through mitochondrial alterations and oxidative stress, altered energy and glucose metabolism, cholesterol modifications, dysfunctional protein O-GlcNAcylation, formation of amyloid plaques, altered Aβ metabolism and tau hyperphosphorylation. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: T2DM and AD, both in terms of intracellular signalling and potential therapeutic approach.

scholarly journals Skeletal muscle insulin resistance: role of mitochondria and other ROS sources

2017 ◽  
Vol 233 (1) ◽  
pp. R15-R42 ◽  
Author(s):  
Sergio Di Meo ◽  
Susanna Iossa ◽  
Paola Venditti
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Early Event ◽  
Ros Production ◽  
Obese People ◽  
Skeletal Muscle Insulin Resistance ◽  
Mitochondrial Alterations

At present, obesity is one of the most important public health problems in the world because it causes several diseases and reduces life expectancy. Although it is well known that insulin resistance plays a pivotal role in the development of type 2 diabetes mellitus (the more frequent disease in obese people) the link between obesity and insulin resistance is yet a matter of debate. One of the most deleterious effects of obesity is the deposition of lipids in non-adipose tissues when the capacity of adipose tissue is overwhelmed. During the last decade, reduced mitochondrial function has been considered as an important contributor to ‘toxic’ lipid metabolite accumulation and consequent insulin resistance. More recent reports suggest that mitochondrial dysfunction is not an early event in the development of insulin resistance, but rather a complication of the hyperlipidemia-induced reactive oxygen species (ROS) production in skeletal muscle, which might promote mitochondrial alterations, lipid accumulation and inhibition of insulin action. Here, we review the literature dealing with the mitochondria-centered mechanisms proposed to explain the onset of obesity-linked IR in skeletal muscle. We conclude that the different pathways leading to insulin resistance may act synergistically because ROS production by mitochondria and other sources can result in mitochondrial dysfunction, which in turn can further increase ROS production leading to the establishment of a harmful positive feedback loop.

Sex differences in CSF biomarkers vary by Alzheimer disease stage and APOE ε4 genotype

Neurology ◽  
2020 ◽  
Vol 95 (17) ◽  
pp. e2378-e2388 ◽  
Author(s):  
Rosha Babapour Mofrad ◽  
Betty M. Tijms ◽  
Philip Scheltens ◽  
Frederik Barkhof ◽  
Wiesje M. van der Flier ◽  
...  
Keyword(s):  
Sex Differences ◽  
Alzheimer Disease ◽  
Clinical Disease ◽  
Disease Stage ◽  
Subjective Cognitive Decline ◽  
Csf Biomarkers ◽  
Β Amyloid ◽  
Disease Stages ◽  
T Tau

ObjectiveTo evaluate sex differences in CSF biomarkers, taking the potential modifying role of clinical disease stage and APOE ε4 genotype into account.MethodWe included participants (n = 1,801) with probable Alzheimer disease (AD) dementia (n = 937), mild cognitive impairment (MCI; n = 437), and subjective cognitive decline (SCD; n = 427). Main outcomes were CSF β-amyloid1–42 (Aβ42), total tau (t-Tau), and tau phosphorylated at threonine 181 (p-Tau) levels. Age-corrected 3-way interactions between sex, disease stage (i.e., syndrome diagnosis at baseline), and APOE ε4 were tested with linear regression analyses for each outcome measure. In case of significant interactions (p < 0.05), sex differences were further evaluated by stratifying analyses for clinical disease stage and APOE ε4 genotype, including age as a covariate.ResultsThree-way interactions were significant for t-Tau (p < 0.001) and p-Tau (p < 0.01) but not Aβ42. In APOE ε4 carriers, women showed higher p-Tau concentrations than men in SCD (Cohen d [95% confidence interval]: t-Tau = 0.52 [0.19–0.84], p < 0.001; p-Tau = 0.44 [0.11–0.77] p = 0.004) and MCI (Cohen d [95% CI]: t-Tau = 0.54 [0.28–0.80], p < 0.001; p-Tau = 0.52 [0.26–0.77], p < 0.001) but not in AD dementia. In APOE ε4 noncarriers, women showed higher p-Tau concentrations in MCI (Cohen d [95% CI]: t-Tau = 0.49 [0.17–0.80], p = 0.002; p-Tau = 0.47 [0.16–0.78], p = 0.003) and AD dementia (Cohen d [95% CI]: t-Tau = 0.42 [0.19–0.65], p < 0.001; p-Tau = 0.38 [0.15–0.61] p = 0.002) but not in SCD.ConclusionsWithin APOE ε4 carriers, sex differences in CSF p-Tau are more evident in early disease stages, whereas for APOE ε4 noncarriers, sex differences are more evident in advanced disease stages. These findings suggest that the effect of APOE ε4 on sex differences in CSF biomarkers depends on disease stage in AD.

scholarly journals Sex differences in β-amyloid accumulation in 3xTg-AD mice: Role of neonatal sex steroid hormone exposure

2010 ◽  
Vol 1366 ◽  
pp. 233-245 ◽  
Author(s):  
Jenna C. Carroll ◽  
Emily R. Rosario ◽  
Sara Kreimer ◽  
Angela Villamagna ◽  
Elisabet Gentzschein ◽  
...  
Keyword(s):  
Sex Differences ◽  
Steroid Hormone ◽  
Sex Steroid ◽  
Sex Steroid Hormone ◽  
Amyloid Accumulation ◽  
Hormone Exposure ◽  
Β Amyloid

Alzheimer’s disease pathogenesis is dependent on neuronal receptor PTPσ

2016 ◽  
Author(s):  
Yuanzheng Gu ◽  
Yaoling Shu ◽  
Angela W. Corona ◽  
Kui Xu ◽  
Allen F. Yi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Behavioral Deficits ◽  
Amyloid Accumulation ◽  
Β Amyloid ◽  
Neuronal Receptor ◽  
Tau Aggregation

β-amyloid accumulation and Tau aggregation are hallmarks of Alzheimer’s disease, yet their underlying molecular mechanisms remain obscure, hindering therapeutic advances. Here we report that neuronal receptor PTPσ mediates both β-amyloid and Tau pathogenesis in two mouse models. In the brain, PTPσ binds to β-amyloid precursor protein (APP). Depletion of PTPσ reduces the affinity between APP and β-secretase, diminishing APP proteolytic products by β- and γ-cleavage without affecting other major substrates of the secretases, suggesting a specificity of β-amyloidogenic regulation. In human APP transgenic mice during aging, the progression of β-amyloidosis, Tau aggregation, neuroinflammation, synaptic loss, as well as behavioral deficits, all show unambiguous dependency on the expression of PTPσ. Additionally, the aggregates of endogenous Tau are found in a distribution pattern similar to that of early stage neurofibrillary tangles in Alzheimer brains. Together, these findings unveil a gatekeeping role of PTPσ upstream of the degenerative pathogenesis, indicating a potential for this neuronal receptor as a drug target for Alzheimer’s disease.

scholarly journals Protective Role of Foeniculum vulgare Mill. in Brain Disorders; A New Window

2020 ◽  
pp. 131-140
Author(s):  
Afshan Abbas ◽  
Rahila Ikram ◽  
Saadia Iftikhar ◽  
Qurrat ul Ain Bukhari ◽  
Uzair Nisar ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Disease Model ◽  
Study Groups ◽  
Protective Role ◽  
Control Group ◽  
Foeniculum Vulgare ◽  
Herbal Products

Aims: Alzheimer disease and epilepsy are two of the central nervous system (CNS) disorders that not only affect the quality of life of patients but also of family members and caretakers. Remedies for these illnesses are available in allopathic medicines but not without side effects. Herbal products are being investigated for these ailments. Protective role of Foeniculum vulgare Mill. was assessed in this study. Study Design: Laboratory based randomized controlled trial. Place and Duration of Study: Conducted in Pharmacology Department of University of Karachi, between March 2018 and April 2018. Methodology: Mice and rats were divided in three groups, control, 2% and 4% F. vulgare groups, each containing 10 rodents. Control group was fed standard rodent diet, whereas, study groups were given 2% and 4% F. vulgare seeds (crushed) incorporated in standard rodent diet. Epilepsy model was made for mice and Alzheimer disease study was done using rats and passive avoidance test. Results: Lower incidence of seizures and mortality in both study groups as compared to control in epilepsy model and memory retaining effect in both treated groups in Alzheimer disease model was recorded with statistical significance. Conclusion: Clinical studies should be conducted to validate the protective role of this herb in these disorders.

scholarly journals Searching the Missing Link Between Alzheimer’s Disease and Diabetes

2013 ◽  
Vol 20 (2) ◽  
pp. 177-181
Author(s):  
Adina Mitrea ◽  
Simona Georgiana Popa ◽  
Cristina Muntean ◽  
Andreea Soare ◽  
Laura Trotta ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Alzheimer Disease ◽  
Per Se ◽  
Type 3 ◽  
Term Type

Abstract Recent studies strongly suggest a significant association between diabetes mellitus and Alzheimer Disease (AD) justifying the term “type 3 diabetes”. Studies show that impairment of glucose metabolism occurs very early in the course of AD, leading to a broad range of consequences, among which the accumulation of amyloid beta (Aβ), which per se induces insulin resistance. Furthermore, adipocytokines, recognised markers of insulin resistance, seem to play a role in the development of AD. As for insulin resistance, when AD is considered, the most studied ones are leptin and adiponectin, but also a recently described adipokine - progranulin. It is our belief that both prospective and transversal studies on subjects with both AD and type 2 diabetes (T2D) may prove the role of adipokines not only in AD, but also in this most somber association.

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