scholarly journals A novel interaction between AD risk genes synaptojanin 1 and reticulon‐3 potentially impacts synaptic function and endo‐lysosomal trafficking during disease development and progression

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Dongming Cai ◽  
Min Huang ◽  
Jiqing Cao ◽  
Jianwei Hou ◽  
Li Zhu ◽  
...  
Keyword(s):  
Synaptic Function ◽  
Disease Development ◽  
Risk Genes ◽  
Lysosomal Trafficking ◽  
Synaptojanin 1

scholarly journals Module analysis using single-patient differential expression signatures improve the power of association study for Alzheimer’s disease

2020 ◽  
Author(s):  
Jialan Huang ◽  
Dong Lu ◽  
Guofeng Meng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Expression ◽  
Association Studies ◽  
Clinical Manifestations ◽  
Synaptic Function ◽  
Causal Mechanism ◽  
Single Patient ◽  
Risk Genes ◽  
Module Analysis

AbstractThe causal mechanism of Alzheimer’s disease is extremely complex. It usually requires a huge number of samples to achieve a good statistical power in association studies. In this work, we illustrated a different strategy to identify AD risk genes by clustering AD patients into modules based on their single-patient differential expression signatures. Evaluation suggested that our method could enrich AD patients with common clinical manifestations. Applying it to a cohort of only 310 AD patients, we identified 175 AD risk loci at a strict threshold of empirical p < 0.05 while only two loci were identified using all the AD patients. As an evaluation, we collected 23 AD risk genes reported in a recent large-scale meta-analysis and found that 18 of them were re-discovered by association studies using clustered AD patients, while only three of them were re-discovered using all AD patients. Functional annotation suggested that AD associated genetic variants mainly disturbed neuronal/synaptic function. Our results suggested module analysis, even randomly clustering, helped to enrich AD patients affected by the common risk variants.

scholarly journals Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luye Qin ◽  
Jamal B. Williams ◽  
Tao Tan ◽  
Tiaotiao Liu ◽  
Qing Cao ◽  
...  
Keyword(s):  
Risk Factor ◽  
Prefrontal Cortex ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Treatment Strategies ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Brain Diseases ◽  
Risk Genes

AbstractASH1L, a histone methyltransferase, is identified as a top-ranking risk factor for autism spectrum disorder (ASD), however, little is known about the biological mechanisms underlying the link of ASH1L haploinsufficiency to ASD. Here we show that ASH1L expression and H3K4me3 level are significantly decreased in the prefrontal cortex (PFC) of postmortem tissues from ASD patients. Knockdown of Ash1L in PFC of juvenile mice induces the downregulation of risk genes associated with ASD, intellectual disability (ID) and epilepsy. These downregulated genes are enriched in excitatory and inhibitory synaptic function and have decreased H3K4me3 occupancy at their promoters. Furthermore, Ash1L deficiency in PFC causes the diminished GABAergic inhibition, enhanced glutamatergic transmission, and elevated PFC pyramidal neuronal excitability, which is associated with severe seizures and early mortality. Chemogenetic inhibition of PFC pyramidal neuronal activity, combined with the administration of GABA enhancer diazepam, rescues PFC synaptic imbalance and seizures, but not autistic social deficits or anxiety-like behaviors. These results have revealed the critical role of ASH1L in regulating synaptic gene expression and seizures, which provides insights into treatment strategies for ASH1L-associated brain diseases.

scholarly journals Module Analysis Using Single-Patient Differential Expression Signatures Improves the Power of Association Studies for Alzheimer's Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Jialan Huang ◽  
Dong Lu ◽  
Guofeng Meng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Expression ◽  
Association Studies ◽  
Clinical Manifestations ◽  
Synaptic Function ◽  
Causal Mechanism ◽  
Single Patient ◽  
Risk Genes ◽  
Module Analysis

The causal mechanism of Alzheimer's disease is extremely complex. Achieving great statistical power in association studies usually requires a large number of samples. In this work, we illustrated a different strategy to identify AD risk genes by clustering AD patients into modules based on their single-patient differential expression signatures. The evaluation suggested that our method could enrich AD patients with similar clinical manifestations. Applying this to a cohort of only 310 AD patients, we identified 174 AD risk loci at a strict threshold of empirical p &lt; 0.05, while only two loci were identified using all the AD patients. As an evaluation, we collected 23 AD risk genes reported in a recent large-scale meta-analysis and found that 18 of them were rediscovered by association studies using clustered AD patients, while only three of them were rediscovered using all AD patients. Functional annotation suggested that AD-associated genetic variants mainly disturbed neuronal/synaptic function. Our results suggested module analysis helped to enrich AD patients affected by the common risk variants.

Postsynaptic neuronal geometry and synaptic effectiveness

1987 ◽  
Vol 45 ◽  
pp. 690-697
Author(s):  
C.J. Wilson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Function ◽  
Postsynaptic Neuron ◽  
Synaptic Inputs ◽  
Partial Analysis ◽  
Postsynaptic Cell ◽  
Neuronal Geometry ◽  
The Relationship ◽  
Complex Scale

Most central nervous system neurons receive synaptic input from hundreds or thousands of other neurons, and the computational function of such neurons results from the interactions of inputs on a large and complex scale. In most situations that have yielded to a partial analysis, the synaptic inputs to a neuron are not alike in function, but rather belong to distinct categories that differ qualitatively in the nature of their effect on the postsynaptic cell, and quantitatively in the strength of their influence. Many factors have been demonstrated to contribute to synaptic function, but one of the simplest and best known of these is the geometry of the postsynaptic neuron. The fundamental nature of the relationship between neuronal shape and synaptic effectiveness was established on theoretical grounds prior to its experimental verification.

Three-dimensional structure of dendritic spines, neuronal specializations that impart both stability and flexibility to synaptic function

1993 ◽  
Vol 51 ◽  
pp. 92-93
Author(s):  
Kristen M. Harris
Keyword(s):  
Dendritic Spines ◽  
Three Dimensional ◽  
Synaptic Function ◽  
Dimensional Structure ◽  
Excitatory Synapses ◽  
Concept Of Function ◽  
Section Electron ◽  
High Quality Information ◽  
The Central Nervous System ◽  
Mathematical Analyses

Dendritic spines are the tiny protrusions that stud the surface of many neurons and they are the location of over 90% of all excitatory synapses that occur in the central nervous system. Their small size and variable shapes has in large part made detailed study of their structure refractory to conventional light microscopy and single section electron microscopy (EM). Yet their widespread occurrence and likely involvement in learning and memory has motivated extensive efforts to obtain quantitative descriptions of spines in both steady state and dynamic conditions. Since the seminal mathematical analyses of D’Arcy Thompson, the power of establishing quantitatively key parameters of structure has become recognized as a foundation of successful biological inquiry. For dendritic spines highly precise determinations of structure and its variation are proving themselves as the kingpin for establishing a valid concept of function. The recent conjunction of high quality information about the structure, function, and theoretical implications of dendritic spines has produced a flurry of new considerations of their role in synaptic transmission.

Effects of High BMI on Synaptic Function and Metabolic Connectivity in the Brain—Evidence of Gender Difference

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 363-OR ◽  
Author(s):  
ARIANNA SALA ◽  
MAURA MALPETTI ◽  
ANNA FERRULLI ◽  
LUIGI GIANOLLI ◽  
LIVIO LUZI ◽  
...  
Keyword(s):  
Gender Difference ◽  
Synaptic Function ◽  
Metabolic Connectivity ◽  
The Brain ◽  
High Bmi

RESISTANCE TO MILDEW OF SELECTION FAMILY OF RED CURRANT THE BELAYA POTAPENKO × № 1426-21-80

1970 ◽  
pp. 38-40
Author(s):  
O. O. Kalinina ◽  
O. D. Golyaeva ◽  
O. V. Panfilova ◽  
А. V. Pikunova
Keyword(s):  
Powdery Mildew ◽  
Field Resistance ◽  
Disease Development ◽  
Artificial Infection ◽  
Sources Of Resistance ◽  
Climate Conditions ◽  
High Productivity ◽  
Local Soil ◽  
The Family ◽  
Red Currant

Powdery mildew is one of the most harmful fungal diseases that causes economically significant damage to berry plantations. The disease is common in all areas of currant cultivation in the Russian Federation. In this regard, in modern conditions of intensive berry growing, the problem of breeding cultivars that are highly resistant to diseases and pests becomes urgent. Breeders have a difficult task to combine the adaptive potential of the cultivar with its annual high productivity and resistance to biotic environmental factors. When studying the adaptability of introduced cultivars of red currant and selected forms of the Institute to local soil and climate conditions, the following cultivars were identified as sources of economic and useful characteristics and involved in selection: ‘Belaya Potapenko’ as a complex source of resistance powdery mildew and high marketable and taste qualities of berries; SS 1426-21-80 as a source of high productivity and long racemes (raceme length 11-13 cm; up to 20 berries in the raceme). On their base the selection family of red currant has been developed: Belaya Potapenko × ♂SS 1426-21-80. The study of data on the destruction of hybrid seedlings of the selection family by powdery mildew showed that in epiphytotic conditions, the percentage of intensity of the disease development varies over the periods of screening from 0.2% in May to 20.4% in June. Such indicators served as a prerequisite for conducting a comparative test of breeding material in the field under artificial infection with powdery mildew. After artificial infection on the background of epiphytosis, the rate of intensity of the disease development increased slightly and amounted to 35.6% for the family. There were 30 highly resistant seedlings in the family, 10 of which have remained stable and highly resistant since 2018. In these plants we can assume the presence of the so-called field resistance, controlled by polygens, each of which does not give a visible effect of stability, but with different combinations determines one or another of its degree. Highly resistant seedlings will be used in further breeding studies to identify new sources of resistance to powdery mildew.

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