scholarly journals Inhibition of Adenylate Cyclase of Regeneration-Competent Cells of Nervous Tissue: a Novel Approach for the Treatment of Alcoholic Encephalopathy

2021 ◽  
Vol 12 (2) ◽  
pp. 1547-1560
Keyword(s):  
Adenylate Cyclase ◽  
Subventricular Zone ◽  
Morphological Changes ◽  
Laboratory Animals ◽  
Novel Approach ◽  
Pharmacological Targets ◽  
Urgent Task ◽  
Significant Correction ◽  
Effective Drugs ◽  
The Brain

Researching new pharmacological targets and developing highly effective drugs to treat ethanol-induced encephalopathy is an urgent task of neuroscience and pharmacology. The work aimed to study the neuroprotective and neuroregenerative effects of adenylate cyclase (AC) inhibitors in modeling alcoholic encephalopathy in experimental animals. The morphofunctional repair of the brain and the functioning of progenitors (neural stem cells (NSC) and neuronal-committed progenitors (NCP)) and neuroglial cells (astrocytes, oligodendrocytes, microglial cells) of the subventricular zone of the cerebral hemispheres (SVZ) have been investigated. A significant correction of brain morphological changes, disorders of exploratory behavior, and conditioned reflex activity in laboratory animals under the influence of the AС inhibitor were revealed. Increased proliferation of both types of progenitor cells and accelerated differentiation of the NSC were observed when AC inhibitors were administered to mice with neurodegeneration. Improved neurotrophin secretion by astrocytes and microglia was also identified. The findings show the promise of developing a novel approach to treating alcohol-induced encephalopathy with AC inhibitors.

scholarly journals Identification of conserved transcriptome features between humans and Drosophila in the aging brain utilizing machine learning on combined data from the NIH Sequence Read Archive

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255085
Author(s):  
Joe L. Webb ◽  
Simon M. Moe ◽  
Andrew K. Bolstad ◽  
Elizabeth M. McNeill
Keyword(s):  
Morphological Changes ◽  
Age Groups ◽  
Model Organisms ◽  
Aging Brain ◽  
Sequencing Data ◽  
Genetic Changes ◽  
Age Related ◽  
Novel Approach ◽  
Increased Risk ◽  
The Brain

Aging is universal, yet characterizing the molecular changes that occur in aging which lead to an increased risk for neurological disease remains a challenging problem. Aging affects the prefrontal cortex (PFC), which governs executive function, learning, and memory. Previous sequencing studies have demonstrated that aging alters gene expression in the PFC, however the extent to which these changes are conserved across species and are meaningful in neurodegeneration is unknown. Identifying conserved, age-related genetic and morphological changes in the brain allows application of the wealth of tools available to study underlying mechanisms in model organisms such as Drosophila melanogaster. RNA sequencing data from human PFC and fly heads were analyzed to determine conserved transcriptome signatures of age. Our analysis revealed that expression of 50 conserved genes can accurately determine age in Drosophila (R2 = 0.85) and humans (R2 = 0.46). These transcriptome signatures were also able to classify Drosophila into three age groups with a mean accuracy of 88% and classify human samples with a mean accuracy of 69%. Overall, this work identifies 50 highly conserved aging-associated genetic changes in the brain that can be further studied in model organisms and demonstrates a novel approach to uncovering genetic changes conserved across species from multi-study public databases.

Morphological Changes in the Brain of Acutely Ill and Weight-Recovered Patients with Anorexia Nervosa

2014 ◽  
Vol 42 (1) ◽  
pp. 7-18 ◽  
Author(s):  
Jochen Seitz ◽  
Katharina Bühren ◽  
Georg G. von Polier ◽  
Nicole Heussen ◽  
Beate Herpertz-Dahlmann ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Cognitive Deficits ◽  
Time Course ◽  
Morphological Changes ◽  
Meta Analysis ◽  
Short Term ◽  
Clinical Prognosis ◽  
Qualitative Review ◽  
Brain Changes ◽  
The Brain

Objective: Acute anorexia nervosa (AN) leads to reduced gray (GM) and white matter (WM) volume in the brain, which however improves again upon restoration of weight. Yet little is known about the extent and clinical correlates of these brain changes, nor do we know much about the time-course and completeness of their recovery. Methods: We conducted a meta-analysis and a qualitative review of all magnetic resonance imaging studies involving volume analyses of the brain in both acute and recovered AN. Results: We identified structural neuroimaging studies with a total of 214 acute AN patients and 177 weight-recovered AN patients. In acute AN, GM was reduced by 5.6% and WM by 3.8% compared to healthy controls (HC). Short-term weight recovery 2–5 months after admission resulted in restitution of about half of the GM aberrations and almost full WM recovery. After 2–8 years of remission GM and WM were nearly normalized, and differences to HC (GM: –1.0%, WM: –0.7%) were no longer significant, although small residual changes could not be ruled out. In the qualitative review some studies found GM volume loss to be associated with cognitive deficits and clinical prognosis. Conclusions: GM and WM were strongly reduced in acute AN. The completeness of brain volume rehabilitation remained equivocal.

Conformation as the Therapeutic Target for Neurodegenerative Diseases

2017 ◽  
Vol 14 (4) ◽  
pp. 393-402 ◽  
Author(s):  
Rajaraman Krishnan ◽  
Franz Hefti ◽  
Haim Tsubery ◽  
Michal Lulu ◽  
Ming Proschitsky ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Specific Binding ◽  
Drug Candidate ◽  
High Affinity ◽  
Novel Approach ◽  
Multiple Protein ◽  
Clinical Benefits ◽  
Effective Drugs

Therapeutic strategies that target pathways of protein misfolding and the toxicity of intermediates along these pathways are mainly at discovery and early development stages, with the exception of monoclonal antibodies that have mainly failed to produce convincing clinical benefits in late stage trials. The clinical failures represent potentially critical lessons for future neurodegenerative disease drug development. More effective drugs may be achieved by pursuing the following two strategies. First, conformational targeting of aggregates of misfolded proteins, rather than less specific binding that includes monomer subunits, which vastly outnumber the toxic targets. Second, since neurodegenerative diseases frequently include more than one potential protein pathology, generic targeting of aggregates by shape might also be a crucial feature of a drug candidate. Incorporating both of these critical features into a viable drug candidate along with high affinity binding has not been achieved with small molecule approaches or with antibody fragments. Monoclonal antibodies developed so far are not broadly acting through conformational recognition. Using GAIM (General Amyloid Interaction Motif) represents a novel approach that incorporates high affinity conformational recognition for multiple protein assemblies, as well as recognition of an array of assemblies along the misfolding pathway between oligomers and fibers. A GAIM-Ig fusion, NPT088, is nearing clinical testing.

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.

The Good Sower: A Novel Approach to Teaching Sunday School

2021 ◽  
pp. 073989132199312
Author(s):  
Lisa Marie Anderson-Umana
Keyword(s):  
Daily Life ◽  
Sunday School ◽  
School Students ◽  
The Bible ◽  
Novel Approach ◽  
Approach To Teaching ◽  
The Brain

The problems related to Sunday school students not making the connection between Scripture and daily life and a superficial teaching of the Bible compelled the author to create a novel approach to teaching Sunday school called the “Good Sower.” The imagery of a “Good Sower” is used to teach volunteers how to teach the Bible. Based on solid research regarding how the brain learns, it serves as an overlay in conjunction with published curriculum.

scholarly journals Effects of Brain Size on Adult Neurogenesis in Shrews

2021 ◽  
Vol 22 (14) ◽  
pp. 7664
Author(s):  
Katarzyna Bartkowska ◽  
Krzysztof Turlejski ◽  
Beata Tepper ◽  
Leszek Rychlik ◽  
Peter Vogel ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Molecular Mechanisms ◽  
Brain Size ◽  
Hippocampal Formation ◽  
Small Animals ◽  
Suncus Murinus ◽  
The Brain ◽  
Neomys Fodiens ◽  
Migratory Stream

Shrews are small animals found in many different habitats. Like other mammals, adult neurogenesis occurs in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus (DG) of the hippocampal formation. We asked whether the number of new generated cells in shrews depends on their brain size. We examined Crocidura russula and Neomys fodiens, weighing 10–22 g, and Crocidura olivieri and Suncus murinus that weigh three times more. We found that the density of proliferated cells in the SVZ was approximately at the same level in all species. These cells migrated from the SVZ through the rostral migratory stream to the olfactory bulb (OB). In this pathway, a low level of neurogenesis occurred in C. olivieri compared to three other species of shrews. In the DG, the rate of adult neurogenesis was regulated differently. Specifically, the lowest density of newly generated neurons was observed in C. russula, which had a substantial number of new neurons in the OB compared with C. olivieri. We suggest that the number of newly generated neurons in an adult shrew’s brain is independent of the brain size, and molecular mechanisms of neurogenesis appeared to be different in two neurogenic structures.

scholarly journals Pharmacokinetics and Molecular Modeling Indicate nAChRα4-Derived Peptide HAEE Goes through the Blood–Brain Barrier

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 909
Author(s):  
Yurii A. Zolotarev ◽  
Vladimir A. Mitkevich ◽  
Stanislav I. Shram ◽  
Alexei A. Adzhubei ◽  
Anna P. Tolstova ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Mouse Model ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Laboratory Animals ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Bolus Administration ◽  
Blood Brain ◽  
The Brain

One of the treatment strategies for Alzheimer’s disease (AD) is based on the use of pharmacological agents capable of binding to beta-amyloid (Aβ) and blocking its aggregation in the brain. Previously, we found that intravenous administration of the synthetic tetrapeptide Acetyl-His-Ala-Glu-Glu-Amide (HAEE), which is an analogue of the 35–38 region of the α4 subunit of α4β2 nicotinic acetylcholine receptor and specifically binds to the 11–14 site of Aβ, reduced the development of cerebral amyloidogenesis in a mouse model of AD. In the current study on three types of laboratory animals, we determined the biodistribution and tissue localization patterns of HAEE peptide after single intravenous bolus administration. The pharmacokinetic parameters of HAEE were established using uniformly tritium-labeled HAEE. Pharmacokinetic data provided evidence that HAEE goes through the blood–brain barrier. Based on molecular modeling, a role of LRP1 in receptor-mediated transcytosis of HAEE was proposed. Altogether, the results obtained indicate that the anti-amyloid effect of HAEE, previously found in a mouse model of AD, most likely occurs due to its interaction with Aβ species directly in the brain.

scholarly journals THE PATHOLOGIC EFFECTS OF STREPTOCOCCI FROM CASES OF POLIOMYELITIS AND OTHER SOURCES

1917 ◽  
Vol 25 (4) ◽  
pp. 557-580 ◽  
Author(s):  
Carroll G. Bull
Keyword(s):  
Spinal Cord ◽  
Guinea Pigs ◽  
The Other ◽  
Laboratory Animals ◽  
Histological Changes ◽  
Other Hand ◽  
Brain And Spinal Cord ◽  
The Brain

Streptococci cultivated from the tonsils of thirty-two cases of poliomyelitis were used to inoculate various laboratory animals. In no case was a condition induced resembling poliomyelitis clinically or pathologically in guinea pigs, dogs, cats, rabbits, or monkeys. On the other hand, a considerable percentage of the rabbits and a smaller percentage of some of the other animals developed lesions due to streptococci. These lesions consisted of meningitis, meningo-encephalitis, abscess of the brain, arthritis, tenosynovitis, myositis, abscess of the kidney, endocarditis, pericarditis, and neuritis. No distinction in the character or frequency of the lesions could be determined between the streptococci derived from poliomyelitic patients and from other sources. Streptococci isolated from the poliomyelitic brain and spinal cord of monkeys which succumbed to inoculation with the filtered virus failed to induce in monkeys any paralysis or the characteristic histological changes of poliomyelitis. These streptococci are regarded as secondary bacterial invaders of the nervous organs. Monkeys which have recovered from infection with streptococci derived from cases of poliomyelitis are not protected from infection with the filtered virus, and their blood does not neutralize the filtered virus in vitro. We have failed to detect any etiologic or pathologic relationship between streptococci and epidemic poliomyelitis in man or true experimental poliomyelitis in the monkey.

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