Abstract
At variance with other organs, where the functional and structural units are repeated, the brain is a composite assembly of groups of cells with different metabolic features and functional units. Deterioration of brain function occurs when the number of neurons or their connections decrease below a critical reserve level and coping with environmental stimulation is seriously hampered. Physiopathological alterations of the synaptic junctional areas are reported to play a central role in the process of brain aging. Current research is documenting an age-related numeric loss of synapses which is paired by a significant enlargement of the persisting contact zones: the final outcome of these balanced changes is a significant reduction of the overall synaptic junctional area per unit volume of neuropil. The progressive decline of the mitochondrial metabolic competence, i.e. the capacity of select pools of organelles to provide adequate amounts of adenosine triphosphate is supposed to represent a key determinant in synaptic aging. Cytochemical estimations of the activity of cytochrome oxidase confirm that mitochondrial dysfunctions play an early role in synaptic deterioration. Zinc ions act as physiological neuromodulators at glutamatergic synapses, however, in order to avoid neurotoxic damage, the intracellular free Zn++ concentration ([Zn++]i) must be tightly controlled by: (i) extrusion (Zn++ transporters); (ii) buffering (metallothioneins) and (iii) sequestration (mitochondria) systems. In physiological aging, if any of these systems is impaired and/or not adequately coordinated with the other two, the resulting significant rise of ([Zn++]i) may inhibit the cellular energy providing systems and affect mitochondria as primary target.
| Original language | English |
|---|---|
| Pages (from-to) | 389-393 |
| Number of pages | 5 |
| Journal | Experimental Gerontology |
| Volume | 43 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2008 |
Fingerprint
Keywords
- Brain aging
- Mitochondrial dysfunction
- Mitochondrial metabolic competence
- Synaptic pathology
- Synaptic plasticity
- Zinc homeostasis
ASJC Scopus subject areas
- Ageing
- Medicine(all)
Cite this
Brain aging : The zinc connection. / Bertoni-Freddari, Carlo; Fattoretti, Patrizia; Casoli, Tiziana; Di Stefano, Giuseppina; Giorgetti, Belinda; Balietti, Marta.
In: Experimental Gerontology, Vol. 43, No. 5, 05.2008, p. 389-393.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Brain aging
T2 - The zinc connection
AU - Bertoni-Freddari, Carlo
AU - Fattoretti, Patrizia
AU - Casoli, Tiziana
AU - Di Stefano, Giuseppina
AU - Giorgetti, Belinda
AU - Balietti, Marta
PY - 2008/5
Y1 - 2008/5
N2 - At variance with other organs, where the functional and structural units are repeated, the brain is a composite assembly of groups of cells with different metabolic features and functional units. Deterioration of brain function occurs when the number of neurons or their connections decrease below a critical reserve level and coping with environmental stimulation is seriously hampered. Physiopathological alterations of the synaptic junctional areas are reported to play a central role in the process of brain aging. Current research is documenting an age-related numeric loss of synapses which is paired by a significant enlargement of the persisting contact zones: the final outcome of these balanced changes is a significant reduction of the overall synaptic junctional area per unit volume of neuropil. The progressive decline of the mitochondrial metabolic competence, i.e. the capacity of select pools of organelles to provide adequate amounts of adenosine triphosphate is supposed to represent a key determinant in synaptic aging. Cytochemical estimations of the activity of cytochrome oxidase confirm that mitochondrial dysfunctions play an early role in synaptic deterioration. Zinc ions act as physiological neuromodulators at glutamatergic synapses, however, in order to avoid neurotoxic damage, the intracellular free Zn++ concentration ([Zn++]i) must be tightly controlled by: (i) extrusion (Zn++ transporters); (ii) buffering (metallothioneins) and (iii) sequestration (mitochondria) systems. In physiological aging, if any of these systems is impaired and/or not adequately coordinated with the other two, the resulting significant rise of ([Zn++]i) may inhibit the cellular energy providing systems and affect mitochondria as primary target.
AB - At variance with other organs, where the functional and structural units are repeated, the brain is a composite assembly of groups of cells with different metabolic features and functional units. Deterioration of brain function occurs when the number of neurons or their connections decrease below a critical reserve level and coping with environmental stimulation is seriously hampered. Physiopathological alterations of the synaptic junctional areas are reported to play a central role in the process of brain aging. Current research is documenting an age-related numeric loss of synapses which is paired by a significant enlargement of the persisting contact zones: the final outcome of these balanced changes is a significant reduction of the overall synaptic junctional area per unit volume of neuropil. The progressive decline of the mitochondrial metabolic competence, i.e. the capacity of select pools of organelles to provide adequate amounts of adenosine triphosphate is supposed to represent a key determinant in synaptic aging. Cytochemical estimations of the activity of cytochrome oxidase confirm that mitochondrial dysfunctions play an early role in synaptic deterioration. Zinc ions act as physiological neuromodulators at glutamatergic synapses, however, in order to avoid neurotoxic damage, the intracellular free Zn++ concentration ([Zn++]i) must be tightly controlled by: (i) extrusion (Zn++ transporters); (ii) buffering (metallothioneins) and (iii) sequestration (mitochondria) systems. In physiological aging, if any of these systems is impaired and/or not adequately coordinated with the other two, the resulting significant rise of ([Zn++]i) may inhibit the cellular energy providing systems and affect mitochondria as primary target.
KW - Brain aging
KW - Mitochondrial dysfunction
KW - Mitochondrial metabolic competence
KW - Synaptic pathology
KW - Synaptic plasticity
KW - Zinc homeostasis
UR - http://www.scopus.com/inward/record.url?scp=42049116337&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42049116337&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2007.11.001
DO - 10.1016/j.exger.2007.11.001
M3 - Article
C2 - 18078729
AN - SCOPUS:42049116337
VL - 43
SP - 389
EP - 393
JO - Experimental Gerontology
JF - Experimental Gerontology
SN - 0531-5565
IS - 5
ER -