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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

Integrative model of the impact of aging on the Ca2+ handling mechanisms and physiological processes. During aging there is an interaction between increased oxidative stress and decreased neuron health with mechanisms for Ca2+ regulation including NMDA receptors (NMDAR), voltage-dependent Ca2+ channels (VDCC), intracellular calcium stores (ICS), and Ca2+ buffering and extrusion mechanisms. These changes are region and cell specific rather than representing a global change. An indication of regional specificity (hippocampus, frontal cortex, cortex, basal forebrain) and the direction of change (increase – red arrow and decrease – green arrow) for each mechanism are also provided. The shift in Ca2+ homeostatic mechanisms may represent neuroprotective mechanisms to decrease further rise in intracellular Ca2+ by decreasing neuron activity. These changes also impair the function of the neuron.
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Figure 2: Integrative model of the impact of aging on the Ca2+ handling mechanisms and physiological processes. During aging there is an interaction between increased oxidative stress and decreased neuron health with mechanisms for Ca2+ regulation including NMDA receptors (NMDAR), voltage-dependent Ca2+ channels (VDCC), intracellular calcium stores (ICS), and Ca2+ buffering and extrusion mechanisms. These changes are region and cell specific rather than representing a global change. An indication of regional specificity (hippocampus, frontal cortex, cortex, basal forebrain) and the direction of change (increase – red arrow and decrease – green arrow) for each mechanism are also provided. The shift in Ca2+ homeostatic mechanisms may represent neuroprotective mechanisms to decrease further rise in intracellular Ca2+ by decreasing neuron activity. These changes also impair the function of the neuron.

Mentions: Cell specific susceptibility to Ca2+ dysregulation depends on environmental and genomic factors in addition to the availability of mechanisms for handling Ca2+. The level of neural activity may render some regions more susceptible to oxidative stress, resulting in multiple changes to increase intracellular Ca2+ including increased release of Ca2+ from ICS, impaired Ca2+ pumps, and weakened Ca2+ buffering (Figure 2). In turn, gene mutations may interact with age and cell specific alterations in Ca2+ regulation to produce the pattern of neuronal death which characterizes neurodegenerative diseases.


Susceptibility to Calcium Dysregulation during Brain Aging.

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

Integrative model of the impact of aging on the Ca2+ handling mechanisms and physiological processes. During aging there is an interaction between increased oxidative stress and decreased neuron health with mechanisms for Ca2+ regulation including NMDA receptors (NMDAR), voltage-dependent Ca2+ channels (VDCC), intracellular calcium stores (ICS), and Ca2+ buffering and extrusion mechanisms. These changes are region and cell specific rather than representing a global change. An indication of regional specificity (hippocampus, frontal cortex, cortex, basal forebrain) and the direction of change (increase – red arrow and decrease – green arrow) for each mechanism are also provided. The shift in Ca2+ homeostatic mechanisms may represent neuroprotective mechanisms to decrease further rise in intracellular Ca2+ by decreasing neuron activity. These changes also impair the function of the neuron.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Integrative model of the impact of aging on the Ca2+ handling mechanisms and physiological processes. During aging there is an interaction between increased oxidative stress and decreased neuron health with mechanisms for Ca2+ regulation including NMDA receptors (NMDAR), voltage-dependent Ca2+ channels (VDCC), intracellular calcium stores (ICS), and Ca2+ buffering and extrusion mechanisms. These changes are region and cell specific rather than representing a global change. An indication of regional specificity (hippocampus, frontal cortex, cortex, basal forebrain) and the direction of change (increase – red arrow and decrease – green arrow) for each mechanism are also provided. The shift in Ca2+ homeostatic mechanisms may represent neuroprotective mechanisms to decrease further rise in intracellular Ca2+ by decreasing neuron activity. These changes also impair the function of the neuron.
Mentions: Cell specific susceptibility to Ca2+ dysregulation depends on environmental and genomic factors in addition to the availability of mechanisms for handling Ca2+. The level of neural activity may render some regions more susceptible to oxidative stress, resulting in multiple changes to increase intracellular Ca2+ including increased release of Ca2+ from ICS, impaired Ca2+ pumps, and weakened Ca2+ buffering (Figure 2). In turn, gene mutations may interact with age and cell specific alterations in Ca2+ regulation to produce the pattern of neuronal death which characterizes neurodegenerative diseases.

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