SPECIFIC PROPERTIES OF TUBULIN IN THE PREFRONTAL CORTEX IN CONTROL, SCHIZOPHRENIA AND VASCULAR DEMENTIA

Author(s):  
Burbaeva G.Sh. ◽  
Androsova L.V. ◽  
Vorobyeva E.A. ◽  
Savushkina O.K.

The aim of the study was to evaluate the rate of polymerization of tubulin into microtubules and determine the level of colchicine binding (colchicine-binding activity of tubulin) in the prefrontal cortex in schizophrenia, vascular dementia (VD) and control. Colchicine-binding activity of tubulin was determined by Sherlinе in tubulin-enriched extracts of proteins from the samples. Measurement of light scattering during the polymerization of the tubulin was carried out using the nephelometric method at a wavelength of 450-550 nm. There was a significant decrease in colchicine-binding activity and the rate of tubulin polymerization in the prefrontal cortex in both diseases, and in VD to a greater extent than in schizophrenia. The obtained results suggest that not only in Alzheimer's disease, but also in other mental diseases such as schizophrenia and VD, there is a decrease in the level of tubulin in the prefrontal cortex of the brain, although to a lesser extent than in Alzheimer's disease, and consequently the amount of microtubules.

2020 ◽  
Vol 45 (2) ◽  
Author(s):  
Arpita Chakraborty ◽  
Samir Kumar Praharaj ◽  
R. V. Krishnananda Prabhu ◽  
M. Mukhyaprana Prabhu

AbstractBackgroundMore than half portion of the brain is formed by lipids. They play critical roles in maintaining the brain's structural and functional components. Any dysregulation in these brain lipids can lead to cognitive dysfunction which are associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia, vascular dementia etc. Studies have linked lipids with cognitive impairment. But not much has been studied about the complex brain lipids which might play a pivotal role in cognitive impairment. This review aims to highlight the lipidomic profiles in patients with cognitive dysfunction.ResultsForty-five articles were reviewed. These studies show alterations in complex lipids such as sphingolipids, phospholipids, glycolipids and sterols in brain in various neurological disorders such as vascular dementia, Parkinson's and Alzheimer's disease. However, the classes of fatty acids in these lipids involved are different across studies.ConclusionsThere is a need for targeted lipidomics analysis, specifically including sphingolipids in patients with neurodegenerative disorders so as to improve diagnostics as well as management of these disorders.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 823
Author(s):  
Ekaterina A. Rudnitskaya ◽  
Tatiana A. Kozlova ◽  
Alena O. Burnyasheva ◽  
Natalia A. Stefanova ◽  
Nataliya G. Kolosova

Sporadic Alzheimer’s disease (AD) is a severe disorder of unknown etiology with no definite time frame of onset. Recent studies suggest that middle age is a critical period for the relevant pathological processes of AD. Nonetheless, sufficient data have accumulated supporting the hypothesis of “neurodevelopmental origin of neurodegenerative disorders”: prerequisites for neurodegeneration may occur during early brain development. Therefore, we investigated the development of the most AD-affected brain structures (hippocampus and prefrontal cortex) using an immunohistochemical approach in senescence-accelerated OXYS rats, which are considered a suitable model of the most common—sporadic—type of AD. We noticed an additional peak of neurogenesis, which coincides in time with the peak of apoptosis in the hippocampus of OXYS rats on postnatal day three. Besides, we showed signs of delayed migration of neurons to the prefrontal cortex as well as disturbances in astrocytic and microglial support of the hippocampus and prefrontal cortex during the first postnatal week. Altogether, our results point to dysmaturation during early development of the brain—especially insufficient glial support—as a possible “first hit” leading to neurodegenerative processes and AD pathology manifestation later in life.


2021 ◽  
Vol 18 ◽  
Author(s):  
Panoraia I. Siafaka ◽  
Gökce Mutlu ◽  
Neslihan Üstündağ Okur

Background: Dementia and its related types such as Alzheimer’s disease, vascular dementia and mixed dementia belong to brain associated diseases, resulting in long-term progressive memory loss. These diseases are so severe that can affect a person's daily routine. Up to date, treatment of de- mentias is still an unmet challenge due to their complex pathophysiology and unavailable efficient pharmacological approaches. The use of nanotechnology based pharmaceutical products could possibly improve the management of dementia given that nanocarriers could more efficiently deliver drugs to the brain. Objective: The objective of this study is to provide the current nanotechnology based drug delivery systems for the treatment of various dementia types. In addition, the current diagnosis biomarkers for the mentioned dementia types along with their available pharmacological treatment are being dis- cussed. Method: An extensive review of the current nanosystems such as brain drug delivery systems against Alzheimer’s disease, vascular dementia and mixed dementia was performed. Moreover, nan- otheranostics as possible imaging markers for such dementias were also reported. Results: The field of nanotechnology is quite advantageous for targeting dementia given that nanoscale drug delivery systems easily penetrate the blood brain barrier and circulate in the body for prolonged time. These nanoformulations consist of polymeric nanoparticles, solid lipid nanoparticles, nanostruc- tured lipid carriers, microemulsions, nanoemulsions, and liquid crystals. The delivery of the nan- otherapeutics can be achieved via various administration routes such as transdermal, injectable, oral, and more importantly, through the intranasal route. Nonetheless, the nanocarriers are mostly limited to Alzheimer’s disease targeting; thus, nanocarriers for other types of dementia should be developed. Conclusion: To conclude, understanding the mechanism of neurodegeneration and reviewing the cur- rent drug delivery systems for Alzheimer’s disease and other dementia types are significant for medical and pharmaceutical society to produce efficient therapeutic choices and novel strategies based on mul- tifunctional and biocompatible nanocarriers, which can deliver the drug sufficiently into the brain.


Author(s):  
Kenneth M. Heilman

“Actions speak louder than words.” Although clinician’s behavioral evaluations of dementia most often include assessing episodic memory, declarative memories (e.g., naming and calculating), and executive functions (working memory, letter–word fluency), one of the most important functions of the brain is programing actions, including “how” to move and “when” to move. Patients with Alzheimer’s disease, vascular dementia, and other forms of dementia often have impairments in the systems that mediate these how-apraxic and when-intentional behaviors. Although the presence of these apraxic and action-intentional disorders may help with diagnosis and help doctors gain a better understand these patients’ disability, these functions are rarely tested and are often not well understood. The goal of this chapter is to describe the signs of the various types of apraxic disorders (limb-kinetic, ideomotor, conceptual, ideational, and dissociation) and well as action-intentional disorders (akinesia-hypokinesia, impersistence, perseveration, and defective response inhibition), how to test for these disorders, and their pathophysiology.


2020 ◽  
Author(s):  
Xudong Zhang ◽  
Fatima Trebak ◽  
Lucas AC Souza ◽  
Junchao Shi ◽  
Tong Zhou ◽  
...  

AbstractBackgroundWhile significant advances have been made in uncovering the aetiology of Alzheimer’s disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications are important regulators of complex physiological and pathological processes, including aging, stress responses, and epigenetic inheritance. However, whether small RNAs and their modifications are altered in dementia is not known.MethodsWe performed LC-MS/MS–based, high-throughput assays of small RNA modifications in post-mortem samples of the prefrontal lobe cortices of Alzheimer’s disease (AD) and control individuals. We noted that some of the AD patients has co-occurring vascular cognitive impairment-related pathology (VaD).FindingsWe report altered small RNA modifications in AD samples compared with normal controls. The 15–25-nucleotide (nt) RNA fraction of these samples was enriched for microRNAs, whereas the 30–40-nt RNA fraction was enriched for tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs), and YRNA-derived small RNAs (ysRNAs). Interestingly, most of these altered RNA modifications were detected both in the AD and AD with co-occurring vascular dementia subjects. In addition, sequencing of small RNA in the 30–40-nt fraction from AD cortices revealed reductions in rsRNA-5S, tsRNA-Tyr, and tsRNA-Arg.InterpretationThese data suggest that sncRNAs and their associated modifications are novel signals that may be linked to the pathogenesis and development of Alzheimer’s disease.FundingNIH grants (R01HL122770, R01HL091905, 1P20GM130459, R01HD092431, P50HD098593, GM103440), AHA grant (17IRG33370128), Sigmund Gestetner Foundation Fellowship to P Kehoe.Research in ContextEvidence before this studyAlzheimer’s disease (AD) and vascular dementia (VaD) are marked by cognitive impairment and neuropathologies caused by significant neuronal death. Associated gene mutations are rare in subjects with dementia, and the aetiology of these diseases is still not completely understood. Recent emerging evidence suggests that epigenetic changes are risk factors for the development of dementia. However, studies assessing small RNA modifications—one of the features of epigenetics—in dementia are lacking.Added value of this studyWe used high-throughput liquid chromatography-tandem mass spectrometry and small RNA sequencing to profile small RNA modifications and the composition of small RNAs in post-mortem samples of the prefrontal cortex of AD and control subjects. We detected and quantified 16 types of RNA modifications and identified distinct small non-coding RNAs and modification signatures in AD subjects compared with controls.Implications of all the available evidenceThis study identified novel types and compositions of small RNA modifications in the prefrontal cortex of AD patients compared with control subjects in post-mortem samples. The cellular locations of these RNA modifications and whether they are drivers or outcomes of AD are still not known. However, results from the present study may open new possibilities for dissecting the dementia pathology.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Dongyi Cao ◽  
Dewei Jiang ◽  
Dongming Zhou ◽  
Hong Yu ◽  
Jiali Li

A series of studies have confirmed that DNA methylation disorder (5mC/5hmC) is closely related to the occurrence and development of some diseases, such as Alzheimer’s disease (AD). This study aims at discovering natural compounds that could adjust and control 5-hydroxymethylcytosine (5hmC) levels and improve Alzheimer’s disease (AD) neuronal status. Cordycepin and cordycepic acid were selected as research materials, with resveratrol as positive control. The results of Dot Blot indicated that cordycepin, cordycepic acid, and resveratrol significantly increased the expression level of 5hmC. Combined with qPCR results, it was revealed that cordycepin increased the expression of ten-eleven translocation (TETs) mRNA compared with the abovementioned cordycepic acid and resveratrol. Besides, cordycepin dramatically reduced the transcription level of Apolipoprotein E (ApoE), suggesting that cordycepin might hinder the formation of NFTs (neurofibrillary tangles) and the accumulation of amyloid β-protein (Aβ) in the brain by reducing the expression of ApoE, resulting in affecting the progression of AD. Meanwhile, the immunofluorescence (IF) staining results demonstrated that the percentage of differentiation of SHSY-5Y cells reasonably increased after the treatment of cordycepin and cordycepic acid. Simultaneously, the length of axons and the number of dendritic branches in mouse primary neurons were substantially increased by cordycepin. The screening results illustrated that cordycepin had a positive influence on the level of 5hmC and the morphology of neurons, and most of the effects were better compared to the positive control (resveratrol). It indicated that cordycepin delayed the progression of neurodegenerative diseases such as AD. However, the specific mechanism of action still needs to be further investigated. Our research provided a foundation for further discussion about the influence of cordycepin on AD and a new idea for the pathological study of related diseases.


2021 ◽  
Vol 19 (2) ◽  
pp. 187-207
Author(s):  
Natalia Gawron ◽  
Emilia Łojek ◽  
Beata Hintze ◽  
Anna Rita Egbert

Individuals in the early stages of dementia may demonstrate language difficulties. The aim of the study was an evaluation of the differences in narrative discourse abilities across two types of dementia, i.e., Vascular Dementia (VaD) and Alzheimer’s Disease (AD) in comparison to the young and old elderly. The AD and VaD groups displayed a lower performance than the age-matched YE on tasks involving reasoning. The VaD partici- pants outperformed patients with AD in verbal memory and narrative discourse. Discourse macrostructure analyses showed that the VaD reproduced more propositions than did the AD participants, but that these were comparable to YE and OE. There were more conjunctions in narratives reproduced by the VaD participants as compared to other groups, although this tendency was only present in the story but not in fairy tale reproductions themselves. Individ- uals in the AD group had more difficulties than YE and OE individuals in figuring out the moral of fairy tales. Clinical and control groups reproduced the microstructure and superstructure of texts comparatively well. Discourse recall correlated with performance on verbal memory, attention/working memory, and reasoning. Differences in narrative discourse abilities were found. Alzheimer’s Disease (AD) patients scored lower in verbal memory than did Vascular Dementia (VaD) patients. Both groups however obtained lower results than the young and old elderly.


2021 ◽  
Vol 3 (1) ◽  
pp. 125-128
Author(s):  
Citra Ananta Avis

Dementia is a chronic progressive brain illness syndrome defined by the loss of numerous cognitive processes, including memory, aphasia, apraxia, agnosia, and executive function. Consciousness is usually unaffected. Psychological and behaviour issues are sometimes present. Dementia is caused by a number of diseases and accidents that affect the brain, either directly or indirectly, such as Alzheimer's disease or stroke. Vascular dementia is a loss of thinking capacity caused by disorders that impede blood flow to certain parts of the brain, depriving brain cells of oxygen and nutrients. After Alzheimer's disease, vascular dementia is the second most frequent kind of dementia. This case study looks at a 76-year-old woman who has vascular dementia. The goal of pharmacological management with risperidone in low dose, as well as psychotherapy, in patients is to preserve and maximize function, reduce behaviour problems, relieve caregiver stress, and delay advancement to the next level. Ginkgo Biloba is one of the plants classified as phytopharmacology or medicines derived from of the plant is Ginkgo biloba Plant G. biloba (Gb) is included in the family Ginkgoaceae. In the G. biloba extract has antioxidant, antiviral, anti-inflammatory, and anti-carcinogenic properties. And also have it was stated that G. biloba extract had a good effect on the function of the CNS (central nervous system).


2021 ◽  
Vol 12 ◽  
Author(s):  
Ajneesh Kumar ◽  
Vo Minh Doan ◽  
Balázs Kunkli ◽  
Éva Csősz

The reanalysis of genomics and proteomics datasets by bioinformatics approaches is an appealing way to examine large amounts of reliable data. This can be especially true in cases such as Alzheimer’s disease, where the access to biological samples, along with well-defined patient information can be challenging. Considering the inflammatory part of Alzheimer’s disease, our aim was to examine the presence of antimicrobial and immunomodulatory peptides in human proteomic datasets deposited in the publicly available proteomics database ProteomeXchange (http://www.proteomexchange.org/). First, a unified, comprehensive human antimicrobial and immunomodulatory peptide database, containing all known human antimicrobial and immunomodulatory peptides was constructed and used along with the datasets containing high-quality proteomics data originating from the examination of Alzheimer’s disease and control groups. A throughout network analysis was carried out, and the enriched GO functions were examined. Less than 1% of all identified proteins in the brain were antimicrobial and immunomodulatory peptides, but the alterations characteristic of Alzheimer’s disease could be recapitulated with their analysis. Our data emphasize the key role of the innate immune system and blood clotting in the development of Alzheimer’s disease. The central role of antimicrobial and immunomodulatory peptides suggests their utilization as potential targets for mechanistic studies and future therapies.


Author(s):  
Alifiya Kapasi ◽  
Julia A. Schneider

There are numerous distinct brain pathologies that underlie a clinical diagnosis of dementia. This chapter focuses on the two most common and well-recognized brain pathologies associated with dementia, Alzheimer’s disease and vascular dementia. The authors describe the distinguishing pathological characteristics of Alzheimer’s disease, followed by the pathological hallmarks of vascular dementia including the characteristics of vessel disease and cerebrovascular tissue injuries. The chapter highlights the importance of mixed or co-morbid Alzheimer’s disease and vascular cerebral injury that has been described in multiple clinical pathologic studies, especially in community-based studies. Finally, the authors discuss how data obtained from both clinical and neuropsychological examination of the brain can be integrated.


Sign in / Sign up

Export Citation Format

Share Document