scholarly journals BACE1, a Major Determinant of Selective Vulnerability of the Brain to Amyloid-  Amyloidogenesis, is Essential for Cognitive, Emotional, and Synaptic Functions

2005 ◽  
Vol 25 (50) ◽  
pp. 11693-11709 ◽  
Author(s):  
F. M. Laird
Keyword(s):  
Selective Vulnerability ◽  
Major Determinant ◽  
Synaptic Functions ◽  
The Brain

scholarly journals Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Angela M. Crist ◽  
Kelly M. Hinkle ◽  
Xue Wang ◽  
Christina M. Moloney ◽  
Billie J. Matchett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Digital Pathology ◽  
Selective Vulnerability ◽  
Brain Regions ◽  
Biochemical Analyses ◽  
The Brain ◽  
Relevant Gene ◽  
Tau Expression

AbstractSelective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.

scholarly journals PUFA and their derivatives in neurotransmission and synapses: a new hallmark of synaptopathies

2020 ◽  
Vol 79 (4) ◽  
pp. 388-403
Author(s):  
Mathieu Di Miceli ◽  
Clémentine Bosch-Bouju ◽  
Sophie Layé
Keyword(s):  
Synapse Formation ◽  
Synaptic Function ◽  
Past Century ◽  
High Concentration ◽  
Dietary Pufa ◽  
Synaptic Functions ◽  
Neuropsychiatric Diseases ◽  
Optimal Function ◽  
The Brain

PUFA of the n-3 and n-6 families are present in high concentration in the brain where they are major components of cell membranes. The main forms found in the brain are DHA (22 :6, n-3) and arachidonic acid (20:4, n-6). In the past century, several studies pinpointed that modifications of n-3 and n-6 PUFA levels in the brain through dietary supply or genetic means are linked to the alterations of synaptic function. Yet, synaptopathies emerge as a common characteristic of neurodevelopmental disorders, neuropsychiatric diseases and some neurodegenerative diseases. Understanding the mechanisms of action underlying the activity of PUFA at the level of synapses is thus of high interest. In this frame, dietary supplementation in PUFA aiming at restoring or promoting the optimal function of synapses appears as a promising strategy to treat synaptopathies. This paper reviews the link between dietary PUFA, synapse formation and the role of PUFA and their metabolites in synaptic functions.

scholarly journals 14-3-3 Proteins in Glutamatergic Synapses

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Jiajing Zhang ◽  
Yi Zhou
Keyword(s):  
Synaptic Transmission ◽  
Molecular Pathways ◽  
Glutamatergic Synapses ◽  
Synaptic Functions ◽  
The Future ◽  
Important Regulator ◽  
The Brain

The 14-3-3 proteins are a family of proteins that are highly expressed in the brain and particularly enriched at synapses. Evidence accumulated in the last two decades has implicated 14-3-3 proteins as an important regulator of synaptic transmission and plasticity. Here, we will review previous and more recent research that has helped us understand the roles of 14-3-3 proteins at glutamatergic synapses. A key challenge for the future is to delineate the 14-3-3-dependent molecular pathways involved in regulating synaptic functions.

scholarly journals Liver tryptophan pyrrolase. A major determinant of the lower brain 5-hydroxytryptamine concentration in alcohol-preferring C57BL mice

1989 ◽  
Vol 264 (2) ◽  
pp. 597-599 ◽  
Author(s):  
A A B Badawy ◽  
C J Morgan ◽  
J Lane ◽  
K Dhaliwal ◽  
D M Bradley
Keyword(s):  
Alcohol Consumption ◽  
Major Determinant ◽  
Corticosterone Concentration ◽  
Cba Mice ◽  
C57bl Mice ◽  
Biological Determinants ◽  
Tryptophan Pyrrolase ◽  
The Brain

The lower brain 5-hydroxytryptamine concentration in alcohol-preferring C57BL, compared with -non-preferring CBA, mice is caused by a decrease in circulating tryptophan availability to the brain secondarily to a higher liver tryptophan pyrrolase activity associated with a higher circulating corticosterone concentration. Activity or expression of liver tryptophan pyrrolase and/or their induction by glucocorticoids may be important biological determinants of predisposition to alcohol consumption.

scholarly journals Tau accumulation activates STAT1 triggering memory deficits via suppressing NMDA receptor expression

2018 ◽  
Author(s):  
Xiao-Guang Li ◽  
Xiao-Yue Hong ◽  
Ya-li Wang ◽  
Shu-Juan Zhang ◽  
Jun-Fei Zhang ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nuclear Translocation ◽  
Memory Performance ◽  
Memory Deficits ◽  
Dominant Negative ◽  
Receptor Expression ◽  
Signal Transducer ◽  
Synaptic Functions ◽  
Direct Binding ◽  
The Brain

ABSTRACTIntracellular tau accumulation forming neurofibrillary tangles is hallmark pathology of Alzheimer's disease (AD), but how tau accumulation induces synapse impairment is elusive. By overexpressing human full-length wildtype tau (termed hTau) to mimic tau abnormality as seen in the brain of sporadic AD patients, we found that hTau accumulation activated JAK2 to phosphorylate STAT1 (Signal Transducer and Activator of Transcription 1) at Tyr701 leading to STAT1 dimerization, nuclear translocation and its activation. STAT1 activation suppressed expression of N-methyl-D-aspartate receptors (NMDARs) through direct binding to the specific GAS element of GluN1, GluN2A and GluN2B promoters, while knockdown STAT1 by AAV-Cre in STAT1flox/flox mice or expressing dominant negative Y701F-STAT1 efficiently rescued hTau-induced suppression of NMDARs expression with amelioration of synaptic functions and memory performance. These findings indicate that hTau accumulation impairs synaptic plasticity through JAK2/STAT1-induced suppression of NMDARs expression, revealing a novel mechanism for hTau-associated synapse and memory deficits.

Selective Vulnerability

2017 ◽  
Author(s):  
Robert Laureno
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Brain Structures ◽  
Selective Vulnerability ◽  
Brain Regions ◽  
Degenerative Diseases ◽  
Selective System ◽  
Hereditary Disorders ◽  
The Brain ◽  
Lateral Sclerosis ◽  
Different Parts

This chapter on “Selective Vulnerability” examines the selective vulnerability of different parts of the brain to particular diseases. In one disease, certain areas of brain are particularly vulnerable. In other diseases, different parts of the brain are more susceptible. The concept of selective vulnerability was originally applied to toxic/metabolic and hereditary disorders, but it is also useful in thinking about other neuropathologic processes including neoplastic, infectious, demyelinative, vascular, and traumatic diseases. Diseases can selectively affect brain systems, brain structures, or brain regions. Selective system involvement is clear in degenerative diseases such as amyotrophic lateral sclerosis; selective structure involvement occurs in carbon monoxide’s effect on the globus pallidus; selective region involvement is found in myelinolysis.

Cerebral Palsy

2017 ◽  
Author(s):  
Joan M. Jasien ◽  
Bruce K. Shapiro ◽  
Alexander H. Hoon
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Human Brain ◽  
Selective Vulnerability ◽  
Postnatal Life ◽  
Organizational Changes ◽  
Immature Brain ◽  
The Brain ◽  
Compensatory Plasticity ◽  
Over Time

Cerebral palsy (CP) describes a group of disorders of movement/posture causing activity limitation that are attributed to nonprogressive disturbances in the immature brain that can change over time. The immature human brain undergoes organizational changes during intrauterine and postnatal life creating potential temporal periods of selective vulnerability to damage. Understanding the compensatory plasticity process after the brain injury may provide new insights into the pathogenesis of CP.

Sign in / Sign up

Export Citation Format

Share Document