scholarly journals Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiangpei Yue ◽  
Yanzhao Zhou ◽  
Meng Qiao ◽  
Xingnan Zhao ◽  
Xin Huang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Amyloid Beta ◽  
Cognitive Functions ◽  
Memory Impairment ◽  
Amyloid Plaque ◽  
Morris Water Maze Test ◽  
Gene Expressions ◽  
App Processing ◽  
New Strategy ◽  
The Brain

Abstract Background Alzheimer’s disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model of AD and unravel the mechanism of action of IHT. Methods Six-month-old APPswe/PS1dE9 (APP/PS1) male mice were exposed to hypoxic environment (14.3% O2) 4 h/day for 14 days or 28 days. Cognitive functions were measured by Morris water maze test after either 14 days or 42 days of interval. Thereafter the distribution of amyloid plaque and microglial activation were determined by mouse brain immunohistochemistry, while the amyloid beta (Aβ) and inflammatory cytokines were measured by ELISA and Western Blot. Microarray was used for studying gene expressions in the hippocampus. Results IHT for 14 days or 28 days significantly improved the spatial memory ability of the 6-month-old APP/PS1 mice. The memory improvement by 14 days IHT lasted to 14 days, but not to 42 days. The level of Aβ plaques and neurofilament accumulations was reduced markedly after the IHT exposure. IHT reduced the pro-inflammatory cytokines IL-1β, IL-6 levels, and β-secretase cleavage of APP processing which implies reduced Aβ production. Microarray analysis revealed a large number of genes in the hippocampus were significantly altered which are known to be metabolism-regulated genes. Conclusions This study provides evidence of the beneficial effect of IHT on the progression of AD by alleviating memory impairment, reducing Aβ accumulation and inflammation in the brain. IHT can be developed as a novel measure to relieve the progression of AD by targeting multiple pathways in the AD pathogenesis.

scholarly journals AβPeptide Originated from Platelets Promises New Strategy in Anti-Alzheimer’s Drug Development

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mikhail Y. Inyushin ◽  
Priscila Sanabria ◽  
Legier Rojas ◽  
Yuriy Kucheryavykh ◽  
Lilia Kucheryavykh
Keyword(s):  
Drug Development ◽  
Blood Plasma ◽  
Amyloid Beta ◽  
Blood Cells ◽  
Research Progress ◽  
Future Perspectives ◽  
Amyloid Burden ◽  
New Strategy ◽  
The Brain ◽  
Alternative Theories

The amyloid beta (Aβ) peptide and its deposits in the brain are known to be implicated in the neurodegeneration that occurs during Alzheimer’s disease (AD). Recently, alternative theories views concerning both the source of this peptide and its functions have been developed. It has been shown that, as in all other known types of amyloidosis, the production of Aβoriginates in blood cells or cells related to blood plasma, from which it can then spread from the blood to inside the brain, with the greatest concentration around brain blood vessels. In this review, we summarize research progress in this new area and outline some future perspectives. While it is still unclear whether the main source of Aβdeposits in AD is the blood, the possibility of blocking the chain of reactions that lead to constant Aβrelease from the blood to the brain may be exploited in an attempt to reduce the amyloid burden in AD. Solving the problem of Aβaccumulation in this way may provide an alternative strategy for developing anti-AD drugs.

scholarly journals GFAP Expression in the Cerebral Cortex during the Development of Cerebral Hypoxia in Rats Showing Different Results in the Morris Water Maze

Biomeditsina ◽  
2020 ◽  
Vol 16 (1) ◽  
pp. 89-98
Author(s):  
V. V. Chrishtop ◽  
T. A. Rumyantseva ◽  
D. A. Pozhilov
Keyword(s):  
Morris Water Maze ◽  
Cognitive Functions ◽  
Water Maze ◽  
Cerebrovascular Disorders ◽  
Morris Water Maze Test ◽  
Numerical Density ◽  
Precentral Gyrus ◽  
Learning Abilities ◽  
Brain Data ◽  
The Brain

The state of cognitive functions in cerebrovascular disorders is one of the most urgent healthcare problems. Recently obtained data convincingly indicate the participation of astrocytes in the formation of cognitive functions of the brain. We conducted a study on 88 Wistar rats. Following the results of testing the rats in a Morris water maze, all animals were divided into two subgroups: those with a high (HLA) and low (LLA) level of spatial situational learning abilities in the Morris water maze test. The animals in the experimental group (48 animals) underwent bilateral ligation of both carotid arteries. The animals were removed from the experiment on the 21st, 60th and 90th day after the operation. Glial fibrillar acidic protein (GFAP), a marker of mature astrocytes, was detected using primary polyclonal rabbit antibodies on histological sections of the precentral gyrus of the brain. Data were obtained on a more pronounced decrease in the numerical density of astrocyte bodies and the number of astrocyte main processes in HLA and LLA animals in earlier (on the 21st day) and later (on the 90th day) stages of the experiment, respectively. The growth of the area occupied by the astrocyte processes occurred earlier in HLA animals (on the 60th day after the simulation) compared to LLA animals (on the 90th day after the simulation). The conducted factor analysis confirmed the presence of two factors associated with the dynamics of the studied parameters. The conclusion is made about alternative variants of changes in the studied groups. The HLA subgroup predominantly demonstrated changes of an alterational character in earlier experimental stages, while adaptive changes were observed in the later stages of the experiment. Conversely, in the LLA subgroup, alterations and adaptations occurred in later and earlier experimental stages, respectively.

Fisiopatología de la hidrocefália idiopática de presión normal (parte 3): sistemaa glinfático

2016 ◽  
Vol 21 (2) ◽  
pp. 28-37
Author(s):  
Oscar Solís-Salgado ◽  
José Luis López-Payares ◽  
Mauricio Ayala-González
Keyword(s):  
Amyloid Beta ◽  
Interstitial Fluid ◽  
Amyloid Β ◽  
Bulk Flow ◽  
Polyethylene Glycols ◽  
Brain Interstitial Fluid ◽  
El Sistema ◽  
Arterial Pulsation ◽  
The Brain

Las vías de drenaje solutos del sistema nervioso central (SNC) participan en el recambio de liquido intersticial con el líquido cefalorraquídeo (LIT-LCR), generando un estado de homeostasis. Las alteraciones dentro de este sistema homeostático afectará la eliminación de solutos del espacio intersticial (EIT) como el péptido βa y proteína tau, los cuales son sustancias neurotóxicas para el SNC. Se han utilizado técnicas experimentales para poder analizar el intercambio LIT-LCR, las cuales revelan que este intercambio tiene una estructura bien organizada. La eliminación de solutos del SNC no tiene una estructura anatómica propiamente, se han descubierto vías de eliminación de solutos a través de marcadores florecentes en el espacio subaracnoideo, cisternas de la base y sistema ventricular que nos permiten observar una serie de vías ampliamente distribuidas en el cerebro. El LCR muestra que tiene una función linfática debido a su recambio con el LIT a lo largo de rutas paravasculares. Estos espacios que rodean la superficie arterial así como los espacios de Virchow-Robin y el pie astrocitico junto con la AQP-4, facilitan la entrada de LCR para-arterial y el aclaramiento de LIT para-venoso dentro del cerebro. El flujo y dirección que toma el LCR por estas estructuras, es conducido por la pulsación arterial. Esta función será la que finalmente llevara a la eliminación de estas sustancias neurotóxicas. En base a la dependencia de este flujo para la eliminación de sustancias se propone que el sistema sea llamado “ la Vía Glinfática”. La bibliografía así como las limitaciones que se encuentran en esta revisión están dadas por la metodología de búsqueda que ha sido realizada principalmente en PubMed utilizando los siguientes términos Mesh: Cerebral Arterial Pulsation, the brain via paravascular, drainage of amyloid-beta, bulk flow of brain interstitial fluid, radiolabeled polyethylene glycols and albumin, amyloid-β, the perivascular astroglial sheath, Brain Glymphatic Transport.

Dendrobium officinalis Flower Improves Learning and Reduces Memory Impairment by Mediating Antioxidant Effect and Balancing the Release of Neurotransmitters in Senescent Rats

2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Brain Aging ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Histopathological Analysis ◽  
Hippocampal Damage ◽  
Common Belief ◽  
Mao B ◽  
Positive Effects ◽  
The Brain

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.

Current Strategies and Novel Drug Approaches for Alzheimer Disease

2020 ◽  
Vol 19 (9) ◽  
pp. 676-690 ◽  
Author(s):  
Roma Ghai ◽  
Kandasamy Nagarajan ◽  
Meenakshi Arora ◽  
Parul Grover ◽  
Nazakat Ali ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinergic Neurons ◽  
Amyloid Plaque ◽  
Neural Pathways ◽  
Current Trends ◽  
Personality Changes ◽  
Traditional Therapies ◽  
Novel Drug ◽  
The Brain

Alzheimer’s Disease (AD) is a chronic, devastating dysfunction of neurons in the brain leading to dementia. It mainly arises due to neuronal injury in the cerebral cortex and hippocampus area of the brain and is clinically manifested as a progressive mental failure, disordered cognitive functions, personality changes, reduced verbal fluency and impairment of speech. The pathology behind AD is the formation of intraneuronal fibrillary tangles, deposition of amyloid plaque and decline in choline acetyltransferase and loss of cholinergic neurons. Tragically, the disease cannot be cured, but its progression can be halted. Various cholinesterase inhibitors available in the market like Tacrine, Donepezil, Galantamine, Rivastigmine, etc. are being used to manage the symptoms of Alzheimer’s disease. The paper’s objective is to throw light not only on the cellular/genetic basis of the disease, but also on the current trends and various strategies of treatment including the use of phytopharmaceuticals and nutraceuticals. Enormous literature survey was conducted and published articles of PubMed, Scifinder, Google Scholar, Clinical Trials.org and Alzheimer Association reports were studied intensively to consolidate the information on the strategies available to combat Alzheimer’s disease. Currently, several strategies are being investigated for the treatment of Alzheimer’s disease. Immunotherapies targeting amyloid-beta plaques, tau protein and neural pathways are undergoing clinical trials. Moreover, antisense oligonucleotide methodologies are being approached as therapies for its management. Phytopharmaceuticals and nutraceuticals are also gaining attention in overcoming the symptoms related to AD. The present review article concludes that novel and traditional therapies simultaneously promise future hope for AD treatment.

Sex Differences in Cognition

2019 ◽  
pp. 41-66
Author(s):  
Elizabeth Hampson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sex Differences ◽  
Spatial Cognition ◽  
Sex Steroids ◽  
Cognitive Functions ◽  
Laboratory Animals ◽  
Human Central Nervous System ◽  
The Brain

Organizational and activational effects of sex steroids were first discovered in laboratory animals, but these concepts extend to hormonal actions in the human central nervous system. This chapter begins with a brief overview of how sex steroids act in the brain and how the organizational-activational hypothesis originated in the field of endocrinology. It then reviews common methods used to study these effects in humans. Interestingly, certain cognitive functions appear to be subject to modification by sex steroids, and these endocrine influences may help explain the sex differences often seen in these functions. The chapter considers spatial cognition as a representative example because the spatial family of functions has received the most study by researchers interested in the biological roots of sex differences in cognition. The chapter reviews evidence that supports an influence of both androgens and estrogens on spatial functions, and concludes with a glimpse of where the field is headed.

scholarly journals Development of a New Polymeric Nanocarrier Dedicated to Controlled Clozapine Delivery at the Dopamine D2-Serotonin 5-HT1A Heteromers

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1000
Author(s):  
Sylwia Łukasiewicz
Keyword(s):  
Physicochemical Parameters ◽  
Modern Science ◽  
Dopamine D2 ◽  
Targeted Transport ◽  
First Choice ◽  
New Strategy ◽  
Cell Components ◽  
Second Generation Antipsychotic ◽  
The Brain ◽  
Polymeric Nanocarrier

Clozapine, the second generation antipsychotic drug, is one of the prominent compounds used for treatment of schizophrenia. Unfortunately, use of this drug is still limited due to serious side effects connected to its unspecific and non-selective action. Nevertheless, clozapine still remains the first-choice drug for the situation of drug-resistance schizophrenia. Development of the new strategy of clozapine delivery into well-defined parts of the brain has been a great challenge for modern science. In the present paper we focus on the presentation of a new nanocarrier for clozapine and its use for targeted transport, enabling its interaction with the dopamine D2 and serotonin 5-HT1A heteromers (D2-5-HT1A) in the brain tissue. Clozapine polymeric nanocapsules (CLO-NCs) were prepared using anionic surfactant AOT (sodium docusate) as an emulsifier, and bio-compatible polyelectrolytes such as: poly-L-glutamic acid (PGA) and poly-L-lysine (PLL). Outer layer of the carrier was grafted by polyethylene glycol (PEG). Several variants of nanocarriers containing the antipsychotic varying in physicochemical parameters were tested. This kind of approach may enable the availability and safety of the drug, improve the selectivity of its action, and finally increase effectiveness of schizophrenia therapy. Moreover, the purpose of the manuscript is to cover a wide scope of the issues, which should be considered while designing a novel means for drug delivery. It is important to determine the interactions of a new nanocarrier with many cell components on various cellular levels in order to be sure that the new nanocarrier will be safe and won’t cause undesired effects for a patient.

scholarly journals Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident

2021 ◽  
Vol 22 (15) ◽  
pp. 7847
Author(s):  
Anthony Fringuello ◽  
Philip D. Tatman ◽  
Tadeusz Wroblewski ◽  
John A. Thompson ◽  
Xiaoli Yu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Hemorrhagic Stroke ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Interleukin 7 ◽  
Poor Outcomes ◽  
Patient Prognosis ◽  
The Brain

Background: A major contributor to disability after hemorrhagic stroke is secondary brain damage induced by the inflammatory response. Following stroke, global increases in numerous cytokines—many associated with worse outcomes—occur within the brain, cerebrospinal fluid, and peripheral blood. Extracellular vesicles (EVs) may traffic inflammatory cytokines from damaged tissue within the brain, as well as peripheral sources, across the blood–brain barrier, and they may be a critical component of post-stroke neuroinflammatory signaling. Methods: We performed a comprehensive analysis of cytokine concentrations bound to plasma EV surfaces and/or sequestered within the vesicles themselves. These concentrations were correlated to patient acute neurological condition by the Glasgow Coma Scale (GCS) and to chronic, long-term outcome via the Glasgow Outcome Scale-Extended (GOS-E). Results: Pro-inflammatory cytokines detected from plasma EVs were correlated to worse outcomes in hemorrhagic stroke patients. Anti-inflammatory cytokines detected within EVs were still correlated to poor outcomes despite their putative neuroprotective properties. Inflammatory cytokines macrophage-derived chemokine (MDC/CCL2), colony stimulating factor 1 (CSF1), interleukin 7 (IL7), and monokine induced by gamma interferon (MIG/CXCL9) were significantly correlated to both negative GCS and GOS-E when bound to plasma EV membranes. Conclusions: These findings correlate plasma-derived EV cytokine content with detrimental outcomes after stroke, highlighting the potential for EVs to provide cytokines with a means of long-range delivery of inflammatory signals that perpetuate neuroinflammation after stroke, thus hindering recovery.

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