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Susceptibility to Calcium Dysregulation during Brain Aging.

Kumar A, Bodhinathan K, Foster TC - Front Aging Neurosci (2009)

Bottom Line: Calcium (Ca(2+)) is a highly versatile intracellular signaling molecule that is essential for regulating a variety of cellular and physiological processes ranging from fertilization to programmed cell death.Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence.The nature of altered Ca(2+) homeostasis is cell specific and may represent a deficit or a compensatory mechanism, producing complex patterns of impaired cellular function.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida Gainesville, FL, USA.

ABSTRACT
Calcium (Ca(2+)) is a highly versatile intracellular signaling molecule that is essential for regulating a variety of cellular and physiological processes ranging from fertilization to programmed cell death. Research has provided ample evidence that brain aging is associated with altered Ca(2+) homeostasis. Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence. The current review takes a broader perspective, assessing age-related changes in Ca(2+) sources, Ca(2+) sequestration, and Ca(2+) binding proteins throughout the nervous system. The nature of altered Ca(2+) homeostasis is cell specific and may represent a deficit or a compensatory mechanism, producing complex patterns of impaired cellular function. Incorporating the knowledge of the complexity of age-related alterations in Ca(2+) homeostasis will positively shape the development of highly effective therapeutics to treat brain disorders.

No MeSH data available.


Related in: MedlinePlus

Ca2+ homeostasis in the neuron. Model depicting various Ca2+ sources, sequestrating, buffering mechanisms, and Ca2+ signaling events in a healthy neuron. Indicated are the voltage-dependent Ca2+ channels (VDCC), N-methyl-d-aspartate receptor (NMDAR), and G protein-coupled receptor (GPCR) involved in Ca2+ (red balls) influx into the cytosol (blue dashed arrows). The release of Ca2+ into the cytoplasm also occurs from the intracellular Ca2+ stores (ICS) through inositol (1,4,5)-trisphosphate receptor (IP3R) and ryanodine receptors (RyR). Organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes act as a Ca2+ buffering system, releasing and sequestering Ca2+. Further, the model depicts Ca2+ buffering and extrusion pathways (red dashed arrows), involving Na+/Ca2+ exchanger (NCX) and plasma membrane Ca2+ ATPase (PMCA), sarcoplasmic reticulum Ca2+ ATPases (SERCA), nicotinic acid adenine dinucleotide phosphate (NAADP), various Ca2+ binding proteins (CBP). Mitochondrial permeability transition pore (mPTP) and mitochondrial Na+/Ca2+ exchanger (mNCX) and secretory pathway Ca2+-ATPases (SPCA) contribute to Ca2+ regulation.
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Figure 1: Ca2+ homeostasis in the neuron. Model depicting various Ca2+ sources, sequestrating, buffering mechanisms, and Ca2+ signaling events in a healthy neuron. Indicated are the voltage-dependent Ca2+ channels (VDCC), N-methyl-d-aspartate receptor (NMDAR), and G protein-coupled receptor (GPCR) involved in Ca2+ (red balls) influx into the cytosol (blue dashed arrows). The release of Ca2+ into the cytoplasm also occurs from the intracellular Ca2+ stores (ICS) through inositol (1,4,5)-trisphosphate receptor (IP3R) and ryanodine receptors (RyR). Organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes act as a Ca2+ buffering system, releasing and sequestering Ca2+. Further, the model depicts Ca2+ buffering and extrusion pathways (red dashed arrows), involving Na+/Ca2+ exchanger (NCX) and plasma membrane Ca2+ ATPase (PMCA), sarcoplasmic reticulum Ca2+ ATPases (SERCA), nicotinic acid adenine dinucleotide phosphate (NAADP), various Ca2+ binding proteins (CBP). Mitochondrial permeability transition pore (mPTP) and mitochondrial Na+/Ca2+ exchanger (mNCX) and secretory pathway Ca2+-ATPases (SPCA) contribute to Ca2+ regulation.

Mentions: Ca2+-signaling depends principally on a rapid and transient increase in intracellular Ca2+ concentration through influx of Ca2+ from several sources. In most cells, multiple mechanisms exist whereby elevation in intracellular Ca2+ concentrations may occur. The major sources of intracellular Ca2+ include Ca2+ influx through ligand-gated glutamate receptors, such as N-methyl-d-aspartate (NMDA) receptor (NMDAR) or various voltage-dependent Ca2+ channels (VDCCs), as well as the release of Ca2+ from intracellular stores (Ghosh et al., 1994; Geiger et al., 1995; Berridge, 1998). The relative contribution of these sources will depend on the cell type: neuron, astrocyte, oligodendrocyte or microglia. In the case of neurons, Ca2+ sources will vary depending on their size, transmitter system, and location in neural circuits (i.e., excitatory or inhibitory). Finally, we discuss age-related changes to the other aspect of Ca2+ homeostasis, the Ca2+ buffering and extrusion mechanisms (Figure 1).


Susceptibility to Calcium Dysregulation during Brain Aging.

Kumar A, Bodhinathan K, Foster TC - Front Aging Neurosci (2009)

Ca2+ homeostasis in the neuron. Model depicting various Ca2+ sources, sequestrating, buffering mechanisms, and Ca2+ signaling events in a healthy neuron. Indicated are the voltage-dependent Ca2+ channels (VDCC), N-methyl-d-aspartate receptor (NMDAR), and G protein-coupled receptor (GPCR) involved in Ca2+ (red balls) influx into the cytosol (blue dashed arrows). The release of Ca2+ into the cytoplasm also occurs from the intracellular Ca2+ stores (ICS) through inositol (1,4,5)-trisphosphate receptor (IP3R) and ryanodine receptors (RyR). Organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes act as a Ca2+ buffering system, releasing and sequestering Ca2+. Further, the model depicts Ca2+ buffering and extrusion pathways (red dashed arrows), involving Na+/Ca2+ exchanger (NCX) and plasma membrane Ca2+ ATPase (PMCA), sarcoplasmic reticulum Ca2+ ATPases (SERCA), nicotinic acid adenine dinucleotide phosphate (NAADP), various Ca2+ binding proteins (CBP). Mitochondrial permeability transition pore (mPTP) and mitochondrial Na+/Ca2+ exchanger (mNCX) and secretory pathway Ca2+-ATPases (SPCA) contribute to Ca2+ regulation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874411&req=5

Figure 1: Ca2+ homeostasis in the neuron. Model depicting various Ca2+ sources, sequestrating, buffering mechanisms, and Ca2+ signaling events in a healthy neuron. Indicated are the voltage-dependent Ca2+ channels (VDCC), N-methyl-d-aspartate receptor (NMDAR), and G protein-coupled receptor (GPCR) involved in Ca2+ (red balls) influx into the cytosol (blue dashed arrows). The release of Ca2+ into the cytoplasm also occurs from the intracellular Ca2+ stores (ICS) through inositol (1,4,5)-trisphosphate receptor (IP3R) and ryanodine receptors (RyR). Organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes act as a Ca2+ buffering system, releasing and sequestering Ca2+. Further, the model depicts Ca2+ buffering and extrusion pathways (red dashed arrows), involving Na+/Ca2+ exchanger (NCX) and plasma membrane Ca2+ ATPase (PMCA), sarcoplasmic reticulum Ca2+ ATPases (SERCA), nicotinic acid adenine dinucleotide phosphate (NAADP), various Ca2+ binding proteins (CBP). Mitochondrial permeability transition pore (mPTP) and mitochondrial Na+/Ca2+ exchanger (mNCX) and secretory pathway Ca2+-ATPases (SPCA) contribute to Ca2+ regulation.
Mentions: Ca2+-signaling depends principally on a rapid and transient increase in intracellular Ca2+ concentration through influx of Ca2+ from several sources. In most cells, multiple mechanisms exist whereby elevation in intracellular Ca2+ concentrations may occur. The major sources of intracellular Ca2+ include Ca2+ influx through ligand-gated glutamate receptors, such as N-methyl-d-aspartate (NMDA) receptor (NMDAR) or various voltage-dependent Ca2+ channels (VDCCs), as well as the release of Ca2+ from intracellular stores (Ghosh et al., 1994; Geiger et al., 1995; Berridge, 1998). The relative contribution of these sources will depend on the cell type: neuron, astrocyte, oligodendrocyte or microglia. In the case of neurons, Ca2+ sources will vary depending on their size, transmitter system, and location in neural circuits (i.e., excitatory or inhibitory). Finally, we discuss age-related changes to the other aspect of Ca2+ homeostasis, the Ca2+ buffering and extrusion mechanisms (Figure 1).

Bottom Line: Calcium (Ca(2+)) is a highly versatile intracellular signaling molecule that is essential for regulating a variety of cellular and physiological processes ranging from fertilization to programmed cell death.Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence.The nature of altered Ca(2+) homeostasis is cell specific and may represent a deficit or a compensatory mechanism, producing complex patterns of impaired cellular function.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida Gainesville, FL, USA.

ABSTRACT
Calcium (Ca(2+)) is a highly versatile intracellular signaling molecule that is essential for regulating a variety of cellular and physiological processes ranging from fertilization to programmed cell death. Research has provided ample evidence that brain aging is associated with altered Ca(2+) homeostasis. Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence. The current review takes a broader perspective, assessing age-related changes in Ca(2+) sources, Ca(2+) sequestration, and Ca(2+) binding proteins throughout the nervous system. The nature of altered Ca(2+) homeostasis is cell specific and may represent a deficit or a compensatory mechanism, producing complex patterns of impaired cellular function. Incorporating the knowledge of the complexity of age-related alterations in Ca(2+) homeostasis will positively shape the development of highly effective therapeutics to treat brain disorders.

No MeSH data available.


Related in: MedlinePlus