Dmitry Aronov - Academia.edu (original) (raw)

Papers by Dmitry Aronov

Research paper thumbnail of A high‐fat diet changes astrocytic metabolism to promote synaptic plasticity and behavior

A high‐fat diet changes astrocytic metabolism to promote synaptic plasticity and behavior

Acta Physiologica

Research paper thumbnail of A high-fat diet changes astrocytic metabolism to enhance synaptic plasticity and promote exploratory behavior

SummaryA high-fat diet (HFD) is generally considered to negatively influence the body, the brain,... more SummaryA high-fat diet (HFD) is generally considered to negatively influence the body, the brain, and cognitive abilities. On the other hand, fat and fatty acids are essential for nourishing and constructing brain tissue. Astrocytes are central for lipolysis and fatty acids metabolism. Here we show that exposure of young mice to one month of HFD elevates lipid content and increases the relative amount of reduced cytochromes in astrocytes but not in neurons. Metabolic changes were paralleled with an enlargement of astrocytic territorial domains due to an increased outgrowth of branches and leaflets. Astrocyte remodeling was associated with an increase in expression of ezrin and with no changes in glial fibrillary acidic protein (GFAP), glutamate transporter-1 (GLT-1), and glutamine synthetase (GS). Such physiological (non-reactive) enlargement of astrocytes in the brain active milieu promoted glutamate clearance and long-term potentiation. These changes translated into improved explo...

Research paper thumbnail of α-SYNUCLEINOPATHY FORM IN BLRB-Rb(8.17)1Iem MICE WITH SYMPTOMS OF CATATONIA, AKATHISIA AND PARKINSONISM

Neuroscience for Medicine and Psychology, May 13, 2019

Пациенты с эпилепсией вынуждены хронически применять антиэпилептические препараты (АЭП). Ранее на... more Пациенты с эпилепсией вынуждены хронически применять антиэпилептические препараты (АЭП). Ранее нами было показано увеличение эффективности препарата карбамазепина (КБЗ), включенного в наночастицы PLGA (КБЗ-НЧ) в 30 раз, по сравнению со свободной формой (КБЗ). Хроническое применение КБЗ может оказать влияние на поведение. Для КБЗ показаны нормотимические эффекты, а также снижение двигательной активности и тревожности. Изменение поведения при хроническом приеме КБЗ-НЧ в данном исследовании изучили впервые. Эксперимент проводили на крысах Wistar. Животным из 5 групп (n = 60) в течение 28 дней в хвостовую вену вводили следующие препараты: 1) КБЗ: карбамазепин (раствор в 10% Poloxamer 188) 30 мг/кг; 2) КБЗ-НЧ: КБЗ, включенный наночастицы PLGA (суспензия в 1% Poloxamer 188) 1 мг/кг; 3) ненагруженные наночастицы PLGA (плацебо) в 1% Poloxamer 188. Животные в контрольных группах получали физраствор или 10% Poloxamer 188. Поведение исследовали в тестах «открытое поле» (ОП), «приподнятый крестообразный лабиринт» (ПКЛ) и «Лабиринт Барнс». Животные в группах, получавших плацебо, раствор Poloxamer 188 и физраствор, не отличались от контроля ни по одному из исследованных параметров. В тестах ОП и ПКЛ в группе КБЗ отличий от контроля выявлено не было. Крысы из группы КБЗ-НЧ в тесте ОП показали увеличение двигательной и исследовательской активности, а также снижение тревожности животных. В тесте ПКЛ эта же группа показала увеличение времени нахождения в светлых рукавах лабиринта, что также свидетельствует о снижении тревожности. В тесте «Лабиринт Барнс» животные из группы КБЗ-НЧ в процессе обучения дольше оставались на поверхности лабиринта, что связано с их пониженной тревожностью. Однако, они совершали меньше ошибок в финальном тестировании. Животные из группы КБЗ в процессе обучения не отличались от контроля, однако, в финальном тестировании больше времени тратили на поиск убежища. Таким образом, мы показали, что КБЗ снижает обучаемость животных, в то время как КБЗ-НЧ не только повышает обучаемость, но и снижает тревожность, а также увеличивает двигательную и исследовательскую активность. Вероятно, такие эффекты связаны со способностью наночастиц изменять биораспределение препаратов в головном мозге.

Research paper thumbnail of Glycan-binding profile of DC-like cells

Glycoconjugate Journal, 2019

Modification of vaccine carriers by decoration with glycans can enhance binding to and even targe... more Modification of vaccine carriers by decoration with glycans can enhance binding to and even targeting of dendritic cells (DCs), thus augmenting vaccine efficacy. To find a specific glycan-"vector" it is necessary to know glycan-binding profile of DCs. This task is not trivial; the small number of circulating blood DCs available for isolation hinders screening and therefore advancement of the profiling. It would be more convenient to employ long-term cell cultures or even primary DCs from murine blood. We therefore examined whether THP-1 (human monocyte cell line) and DC2.4 (immature murine DC-like cell line) could serve as a model for human DCs. These cells were probed with a set of glycans previously identified as binding to circulating human CD14 low/-CD16 + CD83 + DCs. In addition, we tested a subpopulation of murine CD14 low/-CD80 + СD11c + CD16 + cells reported as relating to the human CD14 low/-CD16 + CD83 + cells. Manα1-3(Manα1-6)Manβ1-4GlcNAcβ1-4GlcNAcβ bound to both the cell lines and the murine CD14 low/-CD80 + СD11c + CD16 + cells. Primary cells, but not the cell cultures, were capable of binding GalNAcα1-3Galβ (A di), the most potent ligand for binding to human circulating DCs. In conclusion, not one of the studied cell lines proved an adequate model for DCs processes involving lectin binding. Although the glycan-binding profile of BYRB-Rb (8.17)1Iem mouse DCs could prove useful for assessing human DCs, important glycan interactions were missing, a situation which was aggravated when employing cells from the BALB/c strain. Accordingly, one must treat results from murine work with caution when seeking vaccine targeting of human DCs, and certainly should avoid cell lines such as THP-1 and DC2.4 cells.

Research paper thumbnail of Imbalances in cellular immunological parameters in blood predetermine tumor onset in a natural mouse model of breast cancer

Cancer Immunology, Immunotherapy, 2019

The development of new approaches to breast cancer (BC) early diagnosis is an important objective... more The development of new approaches to breast cancer (BC) early diagnosis is an important objective of modern oncology. Although the role of the immune system in cancer initiation process was experimentally well established, the prognostic value of cellular blood immunological parameters (CBIPs) for BC onset prediction was not demonstrated either in clinics or in mouse models. In this study, we focused on revealing informative CBIPs for mammary cancer (MC) onset prediction in the BLRB/BYRB mouse model with a high incidence of natural MC development. Blood samples were collected from 80 aging females of these original mouse strains, 12 basic CBIPs were estimated by flow cytometry. Then mice were followed up for 28 weeks, and the outcome of females (MC diagnosis, death without MC or MC-free survival) was registered. We estimated the patterns of changes in CBIPs with age and in accordance with the outcome. An increasing imbalance in 11 CBIPs during natural aging of females clearly resembled human immunosenescence phenomenon and several patterns corresponded to the results obtained on cancer-free members of BC-affected families. We stratified heterogeneous female population into middle-aged and old subgroups. Low NK-cell levels in middle-aged mice and low B-cell along with high T-helper levels in old mice distinguished females with developed MC from the other groups. We found a reliable correlation of several CBIPs with age at MC diagnosis and survival of cancer-bearing females. Thus, we demonstrated the predictive potential of CBIPs as a basis for the development of prognostic models for BC onset in clinics. Keywords Breast cancer • Mouse model • Immune system • Cellular blood immunological parameters Abbreviations Act. Activated BC Breast cancer (in humans) CBIPs Cellular blood immunological parameters MC Mammary cancer (in mice) SPF Specific-pathogen-free Electronic supplementary material The online version of this article (

Research paper thumbnail of Local Interleukin-2 Immunotherapy of Breast Cancer: Benefit and Risk in a Spontaneous Mouse Model

Pathology & Oncology Research, 2018

Earlier, naturally arising mammary cancer in BLRB female mice was shown to reproduce some key pat... more Earlier, naturally arising mammary cancer in BLRB female mice was shown to reproduce some key pathological characteristics of the familial set of human breast cancer. Then we advanced a novel 3S-paradigm of anticancer research that helped to develop selection criteria and to estimate benefit/risk of local interleukin-2 (IL-2) effects in this spontaneous mouse model. In this paper, the efficacy of single and triple local IL-2 doses is compared using properly selected murine BLRB females based on our previously published data. Only BLRB females bearing spontaneous mammary tumors without subclinical period were used. The tumor growth rate and recipient survival of single and triple IL-2 applications were compared with corresponding parameter values of untreated control. Tumor growth rate was decreased in both experimental groups versus control parameter values. Single IL-2 application resulted in a significant prolongation of the average survival time while triple application caused acute tumor rejection in some females decreasing the survival time of the rest of the recipients. As a result, proper treatment protocol in accurately selected females allowed increasing the complete response rate to 14% in spontaneous mouse model of breast cancer. In conclusion, our approaches may demonstrate the principle methodology developing preselection procedure for breast cancer patients for local IL-2 therapy application.

Research paper thumbnail of Efficiency of Recombinant Thymosin β4 in Spontaneous Mouse Model of Chronic Dermatitis

Bulletin of experimental biology and medicine, 2015

The therapeutic efficiency of recombinant thymosin β4 (rTβ4) synthesized by us was studied in viv... more The therapeutic efficiency of recombinant thymosin β4 (rTβ4) synthesized by us was studied in vivo on spontaneous CBRB mouse model that is adequate to human chronic dermatitis. Three applications of the drug during a week significantly alleviated symptoms of the disease in female mice, and in complex with subsequent antibacterial and antifungal therapy led to a pronounced and lasting (2 months) therapeutic effect. The results attest to a possibility of using rTβ4 in combination with the known treatment protocols for chronic inflammatory diseases of the skin.

Research paper thumbnail of A high‐fat diet changes astrocytic metabolism to promote synaptic plasticity and behavior

A high‐fat diet changes astrocytic metabolism to promote synaptic plasticity and behavior

Acta Physiologica

Research paper thumbnail of A high-fat diet changes astrocytic metabolism to enhance synaptic plasticity and promote exploratory behavior

SummaryA high-fat diet (HFD) is generally considered to negatively influence the body, the brain,... more SummaryA high-fat diet (HFD) is generally considered to negatively influence the body, the brain, and cognitive abilities. On the other hand, fat and fatty acids are essential for nourishing and constructing brain tissue. Astrocytes are central for lipolysis and fatty acids metabolism. Here we show that exposure of young mice to one month of HFD elevates lipid content and increases the relative amount of reduced cytochromes in astrocytes but not in neurons. Metabolic changes were paralleled with an enlargement of astrocytic territorial domains due to an increased outgrowth of branches and leaflets. Astrocyte remodeling was associated with an increase in expression of ezrin and with no changes in glial fibrillary acidic protein (GFAP), glutamate transporter-1 (GLT-1), and glutamine synthetase (GS). Such physiological (non-reactive) enlargement of astrocytes in the brain active milieu promoted glutamate clearance and long-term potentiation. These changes translated into improved explo...

Research paper thumbnail of α-SYNUCLEINOPATHY FORM IN BLRB-Rb(8.17)1Iem MICE WITH SYMPTOMS OF CATATONIA, AKATHISIA AND PARKINSONISM

Neuroscience for Medicine and Psychology, May 13, 2019

Пациенты с эпилепсией вынуждены хронически применять антиэпилептические препараты (АЭП). Ранее на... more Пациенты с эпилепсией вынуждены хронически применять антиэпилептические препараты (АЭП). Ранее нами было показано увеличение эффективности препарата карбамазепина (КБЗ), включенного в наночастицы PLGA (КБЗ-НЧ) в 30 раз, по сравнению со свободной формой (КБЗ). Хроническое применение КБЗ может оказать влияние на поведение. Для КБЗ показаны нормотимические эффекты, а также снижение двигательной активности и тревожности. Изменение поведения при хроническом приеме КБЗ-НЧ в данном исследовании изучили впервые. Эксперимент проводили на крысах Wistar. Животным из 5 групп (n = 60) в течение 28 дней в хвостовую вену вводили следующие препараты: 1) КБЗ: карбамазепин (раствор в 10% Poloxamer 188) 30 мг/кг; 2) КБЗ-НЧ: КБЗ, включенный наночастицы PLGA (суспензия в 1% Poloxamer 188) 1 мг/кг; 3) ненагруженные наночастицы PLGA (плацебо) в 1% Poloxamer 188. Животные в контрольных группах получали физраствор или 10% Poloxamer 188. Поведение исследовали в тестах «открытое поле» (ОП), «приподнятый крестообразный лабиринт» (ПКЛ) и «Лабиринт Барнс». Животные в группах, получавших плацебо, раствор Poloxamer 188 и физраствор, не отличались от контроля ни по одному из исследованных параметров. В тестах ОП и ПКЛ в группе КБЗ отличий от контроля выявлено не было. Крысы из группы КБЗ-НЧ в тесте ОП показали увеличение двигательной и исследовательской активности, а также снижение тревожности животных. В тесте ПКЛ эта же группа показала увеличение времени нахождения в светлых рукавах лабиринта, что также свидетельствует о снижении тревожности. В тесте «Лабиринт Барнс» животные из группы КБЗ-НЧ в процессе обучения дольше оставались на поверхности лабиринта, что связано с их пониженной тревожностью. Однако, они совершали меньше ошибок в финальном тестировании. Животные из группы КБЗ в процессе обучения не отличались от контроля, однако, в финальном тестировании больше времени тратили на поиск убежища. Таким образом, мы показали, что КБЗ снижает обучаемость животных, в то время как КБЗ-НЧ не только повышает обучаемость, но и снижает тревожность, а также увеличивает двигательную и исследовательскую активность. Вероятно, такие эффекты связаны со способностью наночастиц изменять биораспределение препаратов в головном мозге.

Research paper thumbnail of Glycan-binding profile of DC-like cells

Glycoconjugate Journal, 2019

Modification of vaccine carriers by decoration with glycans can enhance binding to and even targe... more Modification of vaccine carriers by decoration with glycans can enhance binding to and even targeting of dendritic cells (DCs), thus augmenting vaccine efficacy. To find a specific glycan-"vector" it is necessary to know glycan-binding profile of DCs. This task is not trivial; the small number of circulating blood DCs available for isolation hinders screening and therefore advancement of the profiling. It would be more convenient to employ long-term cell cultures or even primary DCs from murine blood. We therefore examined whether THP-1 (human monocyte cell line) and DC2.4 (immature murine DC-like cell line) could serve as a model for human DCs. These cells were probed with a set of glycans previously identified as binding to circulating human CD14 low/-CD16 + CD83 + DCs. In addition, we tested a subpopulation of murine CD14 low/-CD80 + СD11c + CD16 + cells reported as relating to the human CD14 low/-CD16 + CD83 + cells. Manα1-3(Manα1-6)Manβ1-4GlcNAcβ1-4GlcNAcβ bound to both the cell lines and the murine CD14 low/-CD80 + СD11c + CD16 + cells. Primary cells, but not the cell cultures, were capable of binding GalNAcα1-3Galβ (A di), the most potent ligand for binding to human circulating DCs. In conclusion, not one of the studied cell lines proved an adequate model for DCs processes involving lectin binding. Although the glycan-binding profile of BYRB-Rb (8.17)1Iem mouse DCs could prove useful for assessing human DCs, important glycan interactions were missing, a situation which was aggravated when employing cells from the BALB/c strain. Accordingly, one must treat results from murine work with caution when seeking vaccine targeting of human DCs, and certainly should avoid cell lines such as THP-1 and DC2.4 cells.

Research paper thumbnail of Imbalances in cellular immunological parameters in blood predetermine tumor onset in a natural mouse model of breast cancer

Cancer Immunology, Immunotherapy, 2019

The development of new approaches to breast cancer (BC) early diagnosis is an important objective... more The development of new approaches to breast cancer (BC) early diagnosis is an important objective of modern oncology. Although the role of the immune system in cancer initiation process was experimentally well established, the prognostic value of cellular blood immunological parameters (CBIPs) for BC onset prediction was not demonstrated either in clinics or in mouse models. In this study, we focused on revealing informative CBIPs for mammary cancer (MC) onset prediction in the BLRB/BYRB mouse model with a high incidence of natural MC development. Blood samples were collected from 80 aging females of these original mouse strains, 12 basic CBIPs were estimated by flow cytometry. Then mice were followed up for 28 weeks, and the outcome of females (MC diagnosis, death without MC or MC-free survival) was registered. We estimated the patterns of changes in CBIPs with age and in accordance with the outcome. An increasing imbalance in 11 CBIPs during natural aging of females clearly resembled human immunosenescence phenomenon and several patterns corresponded to the results obtained on cancer-free members of BC-affected families. We stratified heterogeneous female population into middle-aged and old subgroups. Low NK-cell levels in middle-aged mice and low B-cell along with high T-helper levels in old mice distinguished females with developed MC from the other groups. We found a reliable correlation of several CBIPs with age at MC diagnosis and survival of cancer-bearing females. Thus, we demonstrated the predictive potential of CBIPs as a basis for the development of prognostic models for BC onset in clinics. Keywords Breast cancer • Mouse model • Immune system • Cellular blood immunological parameters Abbreviations Act. Activated BC Breast cancer (in humans) CBIPs Cellular blood immunological parameters MC Mammary cancer (in mice) SPF Specific-pathogen-free Electronic supplementary material The online version of this article (

Research paper thumbnail of Local Interleukin-2 Immunotherapy of Breast Cancer: Benefit and Risk in a Spontaneous Mouse Model

Pathology & Oncology Research, 2018

Earlier, naturally arising mammary cancer in BLRB female mice was shown to reproduce some key pat... more Earlier, naturally arising mammary cancer in BLRB female mice was shown to reproduce some key pathological characteristics of the familial set of human breast cancer. Then we advanced a novel 3S-paradigm of anticancer research that helped to develop selection criteria and to estimate benefit/risk of local interleukin-2 (IL-2) effects in this spontaneous mouse model. In this paper, the efficacy of single and triple local IL-2 doses is compared using properly selected murine BLRB females based on our previously published data. Only BLRB females bearing spontaneous mammary tumors without subclinical period were used. The tumor growth rate and recipient survival of single and triple IL-2 applications were compared with corresponding parameter values of untreated control. Tumor growth rate was decreased in both experimental groups versus control parameter values. Single IL-2 application resulted in a significant prolongation of the average survival time while triple application caused acute tumor rejection in some females decreasing the survival time of the rest of the recipients. As a result, proper treatment protocol in accurately selected females allowed increasing the complete response rate to 14% in spontaneous mouse model of breast cancer. In conclusion, our approaches may demonstrate the principle methodology developing preselection procedure for breast cancer patients for local IL-2 therapy application.

Research paper thumbnail of Efficiency of Recombinant Thymosin β4 in Spontaneous Mouse Model of Chronic Dermatitis

Bulletin of experimental biology and medicine, 2015

The therapeutic efficiency of recombinant thymosin β4 (rTβ4) synthesized by us was studied in viv... more The therapeutic efficiency of recombinant thymosin β4 (rTβ4) synthesized by us was studied in vivo on spontaneous CBRB mouse model that is adequate to human chronic dermatitis. Three applications of the drug during a week significantly alleviated symptoms of the disease in female mice, and in complex with subsequent antibacterial and antifungal therapy led to a pronounced and lasting (2 months) therapeutic effect. The results attest to a possibility of using rTβ4 in combination with the known treatment protocols for chronic inflammatory diseases of the skin.