Vestibular Neuronal Function during Ischemia

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.

Download Full-text

Effect of papaverine on developmental hyperserotonemia induced autism spectrum disorder related behavioural phenotypes by altering markers of neuronal function, inflammation, and oxidative stress in rats

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.13459 ◽

2021 ◽

Author(s):

Kanishk Luhach ◽

Giriraj T. Kulkarni ◽

Vijay P. Singh ◽

Bhupesh Sharma

Keyword(s):

Oxidative Stress ◽

Autism Spectrum Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Neuronal Function ◽

Behavioural Phenotypes ◽

And Oxidative Stress

Download Full-text

Deubiquitylating enzymes in neuronal health and disease

Cell Death and Disease ◽

10.1038/s41419-020-03361-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Fatima Amer-Sarsour ◽

Alina Kordonsky ◽

Yevgeny Berdichevsky ◽

Gali Prag ◽

Avraham Ashkenazi

Keyword(s):

Human Brain ◽

Neurodegenerative Disorders ◽

Structure And Function ◽

Pivotal Role ◽

Protein Homeostasis ◽

Neuronal Function ◽

Health And Disease ◽

And Function

AbstractUbiquitylation and deubiquitylation play a pivotal role in protein homeostasis (proteostasis). Proteostasis shapes the proteome landscape in the human brain and its impairment is linked to neurodevelopmental and neurodegenerative disorders. Here we discuss the emerging roles of deubiquitylating enzymes in neuronal function and survival. We provide an updated perspective on the genetics, physiology, structure, and function of deubiquitylases in neuronal health and disease.

Download Full-text

Ndufs4 ablation decreases synaptophysin expression in hippocampus

Scientific Reports ◽

10.1038/s41598-021-90127-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Subrata Kumar Shil ◽

Yoshiteru Kagawa ◽

Banlanjo Abdulaziz Umaru ◽

Fumika Nanto-Hara ◽

Hirofumi Miyazaki ◽

...

Keyword(s):

Nadh Dehydrogenase ◽

Leigh Syndrome ◽

Mitochondrial Respiratory Chain ◽

Mitochondrial Activity ◽

Mitochondrial Complex ◽

Neuronal Function ◽

Mouse Hippocampus ◽

Extracellular Regulated Kinase ◽

Presynaptic Protein

AbstractAltered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.

Download Full-text

Genetic, Behavioral and Environmental Determinants of Male Longevity in Caenorhabditis elegans

Genetics ◽

10.1093/genetics/154.4.1597 ◽

2000 ◽

Vol 154 (4) ◽

pp. 1597-1610 ◽

Cited By ~ 1

Author(s):

David Gems ◽

Donald L Riddle

Keyword(s):

Caenorhabditis Elegans ◽

Life Span ◽

Wild Type ◽

Neuronal Function ◽

Nematode Caenorhabditis Elegans ◽

Wild Isolate ◽

Young Males ◽

C Elegans ◽

Single Sex ◽

Solitary Males

Abstract Males of the nematode Caenorhabditis elegans are shorter lived than hermaphrodites when maintained in single-sex groups. We observed that groups of young males form clumps and that solitary males live longer, indicating that male-male interactions reduce life span. By contrast, grouped or isolated hermaphrodites exhibited the same longevity. In one wild isolate of C. elegans, AB2, there was evidence of copulation between males. Nine uncoordinated (unc) mutations were used to block clumping behavior. These mutations had little effect on hermaphrodite life span in most cases, yet many increased male longevity even beyond that of solitary wild-type males. In one case, the neuronal function mutant unc-64(e246), hermaphrodite life span was also increased by up to 60%. The longevity of unc-4(e120), unc-13(e51), and unc-32(e189) males exceeded that of hermaphrodites by 70–120%. This difference appears to reflect a difference in sex-specific life span potential revealed in the absence of male behavior that is detrimental to survival. The greater longevity of males appears not to be affected by daf-2, but is influenced by daf-16. In the absence of male-male interactions, median (but not maximum) male life span was variable. This variability was reduced when dead bacteria were used as food. Maintenance on dead bacteria extended both male and hermaphrodite longevity.

Download Full-text