scholarly journals Regulation of Hippocampal Synaptic Function by the Metabolic Hormone, Leptin: Implications for Health and Neurodegenerative Disease

2018 ◽  
Vol 12 ◽  
Author(s):  
Gemma McGregor ◽  
Jenni Harvey
Keyword(s):  
Neurodegenerative Disease ◽  
Synaptic Function ◽  
Metabolic Hormone

The Astrogenic Balance in the Aging Brain

2021 ◽  
Vol 19 ◽  
Author(s):  
Fotis Andromidas ◽  
Saeid Atashpanjeh ◽  
Abigail J. Myers ◽  
Brooke E. MacKinnon ◽  
Melanie M. Shaffer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Neurodegenerative Disease ◽  
Inverse Correlation ◽  
The Elderly ◽  
Synaptic Function ◽  
Aging Brain ◽  
Therapeutic Approaches ◽  
Disease States ◽  
Prevalence Of Cancer

: An inverse correlation between the incidence of cancer and neurodegenerative disease has been observed, with the prevalence of cancer peaking around 60 years of age, then slowly tapering off as neurodegenerative diseases increase in the elderly. Although the diseases rarely occur concurrently, the same genes are differentially expressed between the diseases, with four transcription factors found to be in common for their expression. In the brain, mature astrocytes are the origin of astrocytoma, which make up 58.2% of malignant brain tumors in patients 65 or older, while GFAP+ astrocyte-like neural stem cells from the subventricular zone give rise to glioblastoma and anaplastic astrocytoma, which make up 41.6%. Likewise, in neurodegenerative disease, a decrease in astrocyte density is observed in early disease states, and senescent astrocytes increase. Because astrocytes coordinate synaptic function, astrocyte dysfunction likely contributes to or causes initial synapse loss and cognitive decline seen in neurodegenerative disease. In non-disease states, astrocytes retain their ability to successfully re-enter the cell cycle through adult astrogenesis to maintain the neuroenvironment, and controlled astrocytic proliferation could be an important contributor to neurological function. Disruption to this astrogenic balance could account for the inverse correlation of cell cycle dysregulation resulting in malignant astrocytes and tumorigenesis, and astrocytic senescence and cell death without self-renewal in aging resulting in neurodegenerative disease. The current understanding of the astrocytic roles of the transcription factors that could be the cause of this imbalance will be discussed, as well as possible therapeutic approaches to modulate their expression in the astrocyte.

scholarly journals Dysfunction of Mitochondrial Ca2+ Regulatory Machineries in Brain Aging and Neurodegenerative Diseases

2020 ◽  
Vol 8 ◽  
Author(s):  
Hyunsu Jung ◽  
Su Yeon Kim ◽  
Fatma Sema Canbakis Cecen ◽  
Yongcheol Cho ◽  
Seok-Kyu Kwon
Keyword(s):  
Synaptic Transmission ◽  
Neurodegenerative Disease ◽  
Mitochondrial Permeability Transition ◽  
Brain Aging ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Synaptic Function ◽  
Inner Mitochondrial Membrane

Calcium ions (Ca2+) play critical roles in neuronal processes, such as signaling pathway activation, transcriptional regulation, and synaptic transmission initiation. Therefore, the regulation of Ca2+ homeostasis is one of the most important processes underlying the basic cellular viability and function of the neuron. Multiple components, including intracellular organelles and plasma membrane Ca2+-ATPase, are involved in neuronal Ca2+ control, and recent studies have focused on investigating the roles of mitochondria in synaptic function. Numerous mitochondrial Ca2+ regulatory proteins have been identified in the past decade, with studies demonstrating the tissue- or cell-type-specific function of each component. The mitochondrial calcium uniporter and its binding subunits are major inner mitochondrial membrane proteins contributing to mitochondrial Ca2+ uptake, whereas the mitochondrial Na+/Ca2+ exchanger (NCLX) and mitochondrial permeability transition pore (mPTP) are well-studied proteins involved in Ca2+ extrusion. The level of cytosolic Ca2+ and the resulting characteristics of synaptic vesicle release properties are controlled via mitochondrial Ca2+ uptake and release at presynaptic sites, while in dendrites, mitochondrial Ca2+ regulation affects synaptic plasticity. During brain aging and the progress of neurodegenerative disease, mitochondrial Ca2+ mishandling has been observed using various techniques, including live imaging of Ca2+ dynamics. Furthermore, Ca2+ dysregulation not only disrupts synaptic transmission but also causes neuronal cell death. Therefore, understanding the detailed pathophysiological mechanisms affecting the recently discovered mitochondrial Ca2+ regulatory machineries will help to identify novel therapeutic targets. Here, we discuss current research into mitochondrial Ca2+ regulatory machineries and how mitochondrial Ca2+ dysregulation contributes to brain aging and neurodegenerative disease.

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.

Memory Processes, Aging, Cognitive Decline, and Neurodegenerative Diseases

2006 ◽  
Vol 11 (4) ◽  
pp. 304-311 ◽  
Author(s):  
Lars-Göran Nilsson
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Neurodegenerative Disease ◽  
Genetic Markers ◽  
Brain Activity ◽  
Memory Performance ◽  
Modeling And Simulations ◽  
Aging And Health ◽  
Explained Variance ◽  
Different Levels

This paper presents four domains of markers that have been found to predict later cognitive impairment and neurodegenerative disease. These four domains are (1) data patterns of memory performance, (2) cardiovascular factors, (3) genetic markers, and (4) brain activity. The critical features of each domain are illustrated with data from the longitudinal Betula Study on memory, aging, and health ( Nilsson et al., 1997 ; Nilsson et al., 2004 ). Up to now, early signs regarding these domains have been examined one by one and it has been found that they are associated with later cognitive impairment and neurodegenerative disease. However, it was also found that each marker accounts for only a very small part of the total variance, implying that single markers should not be used as predictors for cognitive decline or neurodegenerative disease. It is discussed whether modeling and simulations should be used as tools to combine markers at different levels to increase the amount of explained variance.

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