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Alterations in Lipid Levels of Mitochondrial Membranes Induced by Amyloid-β: A Protective Role of Melatonin.

Rosales-Corral SA, Lopez-Armas G, Cruz-Ramos J, Melnikov VG, Tan DX, Manchester LC, Munoz R, Reiter RJ - Int J Alzheimers Dis (2012)

Bottom Line: The majority of these studies have been focused on the cytoplasmic membrane; meanwhile the mitochondrial membranes have been less explored.The purpose was to determine how Aβ may be responsible for beginning of a vicious cycle where oxidative stress and alterations in cholesterol, lipids and fatty acids, feed back on each other to cause mitochondrial dysfunction.Melatonin, a well-known antioxidant and neuroimmunomodulator indoleamine, reversed some of these alterations and protected mitochondrial membranes from obvious damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA.

ABSTRACT
Alzheimer pathogenesis involves mitochondrial dysfunction, which is closely related to amyloid-β (Aβ) generation, abnormal tau phosphorylation, oxidative stress, and apoptosis. Alterations in membranal components, including cholesterol and fatty acids, their characteristics, disposition, and distribution along the membranes, have been studied as evidence of cell membrane alterations in AD brain. The majority of these studies have been focused on the cytoplasmic membrane; meanwhile the mitochondrial membranes have been less explored. In this work, we studied lipids and mitochondrial membranes in vivo, following intracerebral injection of fibrillar amyloid-β (Aβ). The purpose was to determine how Aβ may be responsible for beginning of a vicious cycle where oxidative stress and alterations in cholesterol, lipids and fatty acids, feed back on each other to cause mitochondrial dysfunction. We observed changes in mitochondrial membrane lipids, and fatty acids, following intracerebral injection of fibrillar Aβ in aged Wistar rats. Melatonin, a well-known antioxidant and neuroimmunomodulator indoleamine, reversed some of these alterations and protected mitochondrial membranes from obvious damage. Additionally, melatonin increased the levels of linolenic and n-3 eicosapentaenoic acid, in the same site where amyloid β was injected, favoring an endogenous anti-inflammatory pathway.

No MeSH data available.


Related in: MedlinePlus

Aβ stain by immunoelectron microscopy. 36 hours after the intracerebral injection of Aβ tissues from the injected area were obtained and subjected to immunohistochemistry by using a primary polyclonal antibody against Aβ. Deposits of Aβ forming deposits in the extracellular space were revealed by conventional light microscopy (data not shown). Aβ immunoreactivity was then revealed with a 6 nm gold label and observed in a transmission electron microscope which allows us to identify (a) deposits of Aβ within myelin axons (black arrows) and in the vasculature (white arrows). (b) Deposits of Aβ (black arrows) penetrate the axon membranes causing demyelination and appear in the axons. Axons look like bulb onions. (c) Aβ appears within the mitochondria finally, where it forms deposits along the cristae (black arrows) and causes intense inflammation, destruction of membranes, and vacuolization (magnification at 27800x).
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fig1: Aβ stain by immunoelectron microscopy. 36 hours after the intracerebral injection of Aβ tissues from the injected area were obtained and subjected to immunohistochemistry by using a primary polyclonal antibody against Aβ. Deposits of Aβ forming deposits in the extracellular space were revealed by conventional light microscopy (data not shown). Aβ immunoreactivity was then revealed with a 6 nm gold label and observed in a transmission electron microscope which allows us to identify (a) deposits of Aβ within myelin axons (black arrows) and in the vasculature (white arrows). (b) Deposits of Aβ (black arrows) penetrate the axon membranes causing demyelination and appear in the axons. Axons look like bulb onions. (c) Aβ appears within the mitochondria finally, where it forms deposits along the cristae (black arrows) and causes intense inflammation, destruction of membranes, and vacuolization (magnification at 27800x).

Mentions: 12, 24, 36 and 48 hours following the intracerebral injection of fibrillar Aβ, deposits of Aβ forming aggregates were reactive to Aβ polyclonal antibody and revealed by immunohistochemistry. Congophilic amyloid deposits remained visible up to 21 days following the intracerebral injection (data not shown). Tissue sections of 50 μm, obtained with a vibratome, were used for immunoelectron microscopy and the Aβ positive immunoreactions were observed in mitochondria along the membranes and deep in the cristae. The presence of Aβ deposits in mitochondria was accompanied by a significant lost of their architecture, characterized by swelling, broken cristae, lost of membrane integrity, and vacuole formation (Figure 1).


Alterations in Lipid Levels of Mitochondrial Membranes Induced by Amyloid-β: A Protective Role of Melatonin.

Rosales-Corral SA, Lopez-Armas G, Cruz-Ramos J, Melnikov VG, Tan DX, Manchester LC, Munoz R, Reiter RJ - Int J Alzheimers Dis (2012)

Aβ stain by immunoelectron microscopy. 36 hours after the intracerebral injection of Aβ tissues from the injected area were obtained and subjected to immunohistochemistry by using a primary polyclonal antibody against Aβ. Deposits of Aβ forming deposits in the extracellular space were revealed by conventional light microscopy (data not shown). Aβ immunoreactivity was then revealed with a 6 nm gold label and observed in a transmission electron microscope which allows us to identify (a) deposits of Aβ within myelin axons (black arrows) and in the vasculature (white arrows). (b) Deposits of Aβ (black arrows) penetrate the axon membranes causing demyelination and appear in the axons. Axons look like bulb onions. (c) Aβ appears within the mitochondria finally, where it forms deposits along the cristae (black arrows) and causes intense inflammation, destruction of membranes, and vacuolization (magnification at 27800x).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3362052&req=5

fig1: Aβ stain by immunoelectron microscopy. 36 hours after the intracerebral injection of Aβ tissues from the injected area were obtained and subjected to immunohistochemistry by using a primary polyclonal antibody against Aβ. Deposits of Aβ forming deposits in the extracellular space were revealed by conventional light microscopy (data not shown). Aβ immunoreactivity was then revealed with a 6 nm gold label and observed in a transmission electron microscope which allows us to identify (a) deposits of Aβ within myelin axons (black arrows) and in the vasculature (white arrows). (b) Deposits of Aβ (black arrows) penetrate the axon membranes causing demyelination and appear in the axons. Axons look like bulb onions. (c) Aβ appears within the mitochondria finally, where it forms deposits along the cristae (black arrows) and causes intense inflammation, destruction of membranes, and vacuolization (magnification at 27800x).
Mentions: 12, 24, 36 and 48 hours following the intracerebral injection of fibrillar Aβ, deposits of Aβ forming aggregates were reactive to Aβ polyclonal antibody and revealed by immunohistochemistry. Congophilic amyloid deposits remained visible up to 21 days following the intracerebral injection (data not shown). Tissue sections of 50 μm, obtained with a vibratome, were used for immunoelectron microscopy and the Aβ positive immunoreactions were observed in mitochondria along the membranes and deep in the cristae. The presence of Aβ deposits in mitochondria was accompanied by a significant lost of their architecture, characterized by swelling, broken cristae, lost of membrane integrity, and vacuole formation (Figure 1).

Bottom Line: The majority of these studies have been focused on the cytoplasmic membrane; meanwhile the mitochondrial membranes have been less explored.The purpose was to determine how Aβ may be responsible for beginning of a vicious cycle where oxidative stress and alterations in cholesterol, lipids and fatty acids, feed back on each other to cause mitochondrial dysfunction.Melatonin, a well-known antioxidant and neuroimmunomodulator indoleamine, reversed some of these alterations and protected mitochondrial membranes from obvious damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA.

ABSTRACT
Alzheimer pathogenesis involves mitochondrial dysfunction, which is closely related to amyloid-β (Aβ) generation, abnormal tau phosphorylation, oxidative stress, and apoptosis. Alterations in membranal components, including cholesterol and fatty acids, their characteristics, disposition, and distribution along the membranes, have been studied as evidence of cell membrane alterations in AD brain. The majority of these studies have been focused on the cytoplasmic membrane; meanwhile the mitochondrial membranes have been less explored. In this work, we studied lipids and mitochondrial membranes in vivo, following intracerebral injection of fibrillar amyloid-β (Aβ). The purpose was to determine how Aβ may be responsible for beginning of a vicious cycle where oxidative stress and alterations in cholesterol, lipids and fatty acids, feed back on each other to cause mitochondrial dysfunction. We observed changes in mitochondrial membrane lipids, and fatty acids, following intracerebral injection of fibrillar Aβ in aged Wistar rats. Melatonin, a well-known antioxidant and neuroimmunomodulator indoleamine, reversed some of these alterations and protected mitochondrial membranes from obvious damage. Additionally, melatonin increased the levels of linolenic and n-3 eicosapentaenoic acid, in the same site where amyloid β was injected, favoring an endogenous anti-inflammatory pathway.

No MeSH data available.


Related in: MedlinePlus