ANTIAMYLOIDOGENIC EFFECT OF MiR-101 IN EXPERIMENTAL ALZHEIMER’S DISEASE
The aim of the study was to determine the effect of miR-101 on the level of β-amyloid peptide and activation of the cytokine system in the brain regions of animals with an experimental model of Alzheimer’s disease. MiR-101 is the key deactivating operator of mRNA function for the amyloid-β protein p...
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National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2019-06-01
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| Series: | Biotechnologia Acta |
| Subjects: | |
| Online Access: | http://biotechnology.kiev.ua/images/storage/3_2019/sokolik_3_2019.pdf |
| _version_ | 1797766892285329408 |
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| author | V. Sokolik O. Berchenko N. Levicheva S. Shulga |
| author_facet | V. Sokolik O. Berchenko N. Levicheva S. Shulga |
| author_sort | V. Sokolik |
| collection | DOAJ |
| description | The aim of the study was to determine the effect of miR-101 on the level of β-amyloid peptide and activation of the cytokine system in the brain regions of animals with an experimental model of Alzheimer’s disease. MiR-101 is the key deactivating operator of mRNA function for the amyloid-β protein precursor. Hence, miR-101 is capable to suppress its synthesis and amyloidogenic processing. Aged male rats were injected intrahippocampally with single-dose unilaterally of β-amyloid peptide 40 aggregates (15 nmol). After 10 days, nasal administration of the liposomal form of miR-101 or empty liposomes was started. After 10 days of therapy, the level of toxic endogenous form β-amyloid peptide 42 and the activity of the cytokine system were determined by the indicators of tumor necrosis factor α, interleukin-6, and interleukin-10 in neocortex, hippocampus and olfactory bulbs. It was found that in rats, aggregates of exogenous β-amyloid peptide 40 model the amyloidogenic and pro-inflammatory situation after 20 days in the neocortex and hippocampus (a significant increase in the concentrations of β-amyloid peptide 42 by 36% and cytokines by 16–18% in the neocortex, and β-amyloid peptide 42 by 27%, proinflammatory cytokines tumor necrosis factor α, interleukin-6 by 14% in the hippocampus), but not in olfactory bulbs. The ten-day course of nasal therapy of liposomal miR-101 normalized the level of β-amyloid peptide 42 and cytokines: in neocortex, the concentration of endogenous toxic β-amyloid peptide 42 decreased by 33%, in the hippocampus by 15%, and concentration of pro-inflammatory cytokines fell by 11–20%. Thus, nasal therapy of miR-101 in liposomes caused a significant anti-amyloidogenic effect in rats with the Alzheimer’s disease model, whereas its anti-inflammatory effect was primarily due to a decrease in β-amyloid peptide 42 concentration. |
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| institution | Directory Open Access Journal |
| issn | 2410-7751 2410-776X |
| language | English |
| last_indexed | 2024-03-12T20:31:50Z |
| publishDate | 2019-06-01 |
| publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
| record_format | Article |
| series | Biotechnologia Acta |
| spelling | doaj.art-f6ae2e82232841ab8183041ab9cfb67a2023-08-02T00:01:14ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryBiotechnologia Acta2410-77512410-776X2019-06-011234149ANTIAMYLOIDOGENIC EFFECT OF MiR-101 IN EXPERIMENTAL ALZHEIMER’S DISEASEV. Sokolik0O. Berchenko1N. Levicheva2S. Shulga3SI “Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine”, KharkivSI “Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine”, KharkivSI “Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine”, KharkivSI “Institute of Food Biotechnology and Genomics of the National Academy of Sciences of Ukraine”, KyivThe aim of the study was to determine the effect of miR-101 on the level of β-amyloid peptide and activation of the cytokine system in the brain regions of animals with an experimental model of Alzheimer’s disease. MiR-101 is the key deactivating operator of mRNA function for the amyloid-β protein precursor. Hence, miR-101 is capable to suppress its synthesis and amyloidogenic processing. Aged male rats were injected intrahippocampally with single-dose unilaterally of β-amyloid peptide 40 aggregates (15 nmol). After 10 days, nasal administration of the liposomal form of miR-101 or empty liposomes was started. After 10 days of therapy, the level of toxic endogenous form β-amyloid peptide 42 and the activity of the cytokine system were determined by the indicators of tumor necrosis factor α, interleukin-6, and interleukin-10 in neocortex, hippocampus and olfactory bulbs. It was found that in rats, aggregates of exogenous β-amyloid peptide 40 model the amyloidogenic and pro-inflammatory situation after 20 days in the neocortex and hippocampus (a significant increase in the concentrations of β-amyloid peptide 42 by 36% and cytokines by 16–18% in the neocortex, and β-amyloid peptide 42 by 27%, proinflammatory cytokines tumor necrosis factor α, interleukin-6 by 14% in the hippocampus), but not in olfactory bulbs. The ten-day course of nasal therapy of liposomal miR-101 normalized the level of β-amyloid peptide 42 and cytokines: in neocortex, the concentration of endogenous toxic β-amyloid peptide 42 decreased by 33%, in the hippocampus by 15%, and concentration of pro-inflammatory cytokines fell by 11–20%. Thus, nasal therapy of miR-101 in liposomes caused a significant anti-amyloidogenic effect in rats with the Alzheimer’s disease model, whereas its anti-inflammatory effect was primarily due to a decrease in β-amyloid peptide 42 concentration.http://biotechnology.kiev.ua/images/storage/3_2019/sokolik_3_2019.pdfmiR-101β-amyloid peptideamyloidosisAlzheimer’s disease. |
| spellingShingle | V. Sokolik O. Berchenko N. Levicheva S. Shulga ANTIAMYLOIDOGENIC EFFECT OF MiR-101 IN EXPERIMENTAL ALZHEIMER’S DISEASE Biotechnologia Acta miR-101 β-amyloid peptide amyloidosis Alzheimer’s disease. |
| title | ANTIAMYLOIDOGENIC EFFECT OF MiR-101 IN EXPERIMENTAL ALZHEIMER’S DISEASE |
| title_full | ANTIAMYLOIDOGENIC EFFECT OF MiR-101 IN EXPERIMENTAL ALZHEIMER’S DISEASE |
| title_fullStr | ANTIAMYLOIDOGENIC EFFECT OF MiR-101 IN EXPERIMENTAL ALZHEIMER’S DISEASE |
| title_full_unstemmed | ANTIAMYLOIDOGENIC EFFECT OF MiR-101 IN EXPERIMENTAL ALZHEIMER’S DISEASE |
| title_short | ANTIAMYLOIDOGENIC EFFECT OF MiR-101 IN EXPERIMENTAL ALZHEIMER’S DISEASE |
| title_sort | antiamyloidogenic effect of mir 101 in experimental alzheimer s disease |
| topic | miR-101 β-amyloid peptide amyloidosis Alzheimer’s disease. |
| url | http://biotechnology.kiev.ua/images/storage/3_2019/sokolik_3_2019.pdf |
| work_keys_str_mv | AT vsokolik antiamyloidogeniceffectofmir101inexperimentalalzheimersdisease AT oberchenko antiamyloidogeniceffectofmir101inexperimentalalzheimersdisease AT nlevicheva antiamyloidogeniceffectofmir101inexperimentalalzheimersdisease AT sshulga antiamyloidogeniceffectofmir101inexperimentalalzheimersdisease |