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1.
Article in English | MEDLINE | ID: mdl-38478319

ABSTRACT

Inflammation is an essential factor in pulmonary complications of diabetes. Bone marrow (BM)-derived C-kit+ cells have immunomodulatory properties and their transplantation is suggested as a promising strategy for ameliorating diabetes complications. This study evaluated the effect of BM-derived C-kit+ cells on the inflammation signaling pathway in lung tissue of type 2 diabetic male rats. Ten rats were used to extract C-kit cells, and 48 male Wistar rats weighing 180 ± 20 g were randomly divided into four equal groups: (1) Control (Cont), (2) Diabetic (D), (3) Diabetic + C-kit+ cells (D + C-kit pos) intravenously injected 50-µl phosphate buffer saline (PBS) containing 300,000 C-kit+ cells, and (4) Diabetic + C-kit- cells (D + C-kit neg), intravenously injected C-kit- cells. Diabetes induction increased IL-33, ST-2, CD127, and IL-2 levels and decreased IL-10. C-kit+ cell therapy significantly decreased IL-33 and CD127 and increased IL-10. In addition, lung histopathological changes significantly improved in the C-kit+ group compared to the diabetic group. These findings suggest that C-kit+ cells may have a potential therapeutic role in mitigating diabetes-induced respiratory complications via ameliorating the inflammation and histopathological changes in lung tissue.

2.
Iran J Basic Med Sci ; 27(1): 114-121, 2024.
Article in English | MEDLINE | ID: mdl-38164475

ABSTRACT

Objectives: Aging and stress synergistically induce behavioral dysfunctions associated with oxidative and endoplasmic reticulum (ER) stress in brain regions. Considering the rejuvenating effects of young plasma on aging brain function, in the current study, we examined the effects of young plasma administration on anxiety-like behavior, NADH oxidase, NADPH oxidase, and ER stress markers in the hippocampus of old male rats. Materials and Methods: Young (3 months old) and aged (22 months old) rats were randomly assigned into five groups: young control (Y), aged control (A), aged rats subjected to chronic stress for four weeks (A+S), aged rats subjected to chronic stress and treated with old plasma (A+S+OP), and aged rats subjected to chronic stress and treated with young plasma (A+S+YP). Systemic injection of (1 ml) young and old plasma was performed for four weeks (3 times/week). Results: Young plasma transfusion significantly improved anxiety-like behavior in aged rats and modulated oxidative stress in the hippocampus, evidenced by the increased NADH oxidase (NOX) activity and the reduced NADPH oxidase. In addition, the levels of C/EBP homologous protein (CHOP) and Glucose-Regulated Protein 78 (GRP-78), as ER stress markers, markedly reduced in the hippocampus following the administration of young plasma. Conclusion: These findings suggest that young plasma transfusion could reverse anxiety-like behavior in stress-exposed aged rats by modulating the hippocampal oxidative and ER stress markers.

3.
Neurosci Res ; 198: 39-46, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37392834

ABSTRACT

Structural and functional recovery from stress-induced depression is impaired in the context of aging brain. Since investigating the molecular substrates that facilitate behavioral recovery may have important implications for understanding brain plasticity and resilience of individuals, we studied depressive-like behaviors in young and aged rats 6 weeks after chronic stress exposure as a recovery period and examined the levels of TNF-α and IL-6 inflammatory cytokines, NADH oxidase activity, NADPH oxidase, endoplasmic reticulum (ER) stress markers, and apoptosis in the hippocampus. Young (3 months old) and aged (22 months old) male Wistar rats were divided into four groups; young control (Young), depression model of young rats that received chronic stress procedure followed by a 6-week recovery period (Young+S), aged control (Aged), and depression model of aged rats that received chronic stress procedure followed by a 6-week recovery period (Aged+S). After the recovery period, aged but not young rats showed depression-like behaviors, evaluated by the sucrose preference test (SPT) and forced swimming test (FST), coincided with the altered levels of TNF-α, IL-6, NADH oxidase activity, NADPH oxidase, GRP78, CHOP, and cleaved caspase-12 in the hippocampus of these animals. These data suggested that oxidative and ER stress-induced apoptosis in the aging hippocampus may affect the recovery-related outcomes after the stress paradigm.


Subject(s)
Depression , Tumor Necrosis Factor-alpha , Rats , Male , Animals , Depression/etiology , Rats, Wistar , Interleukin-6 , Stress, Psychological/complications , Hippocampus , Endoplasmic Reticulum Stress , NADPH Oxidases , Apoptosis
4.
Mol Cell Biochem ; 479(3): 603-615, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37129768

ABSTRACT

Stem cell-based therapy has been proposed as a novel therapeutic strategy for diabetic nephropathy. This study was designed to evaluate the effect of systemic administration of rat bone marrow-derived c-kit positive (c-kit+) cells on diabetic nephropathy in male rats, focusing on PI3K/AKT/GSK-3ß pathway and apoptosis as a possible therapeutic mechanism. Twenty-eight animals were randomly classified into four groups: Control group (C), diabetic group (D), diabetic group, intravenously received 50 µl phosphate-buffered saline (PBS) containing 3 × 105 c-kit- cells (D + ckit-); and diabetic group, intravenously received 50 µl PBS containing 3 × 105 c-Kit positive cells (D + ckit+). Control and diabetic groups intravenously received 50 µl PBS. C-kit+ cell therapy could reduce renal fibrosis, which was associated with attenuation of inflammation as indicated by decreased TNF-α and IL-6 levels in the kidney tissue. In addition, c-kit+ cells restored the expression levels of PI3K, pAKT, and GSK-3ß proteins. Furthermore, renal apoptosis was decreased following c-kit+ cell therapy, evidenced by the lower apoptotic index in parallel with the increased Bcl-2 and decreased Bax and Caspase-3 levels. Our results showed that in contrast to c-kit- cells, the administration of c-kit+ cells ameliorate diabetic nephropathy and suggested that c-kit+ cells could be an alternative cell source for attenuating diabetic nephropathy.


Subject(s)
Cell- and Tissue-Based Therapy , Diabetic Nephropathies , Animals , Male , Rats , Apoptosis , Bone Marrow/metabolism , Diabetic Nephropathies/therapy , Glycogen Synthase Kinase 3 beta/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Signal Transduction , Stem Cells/metabolism , Proto-Oncogene Proteins c-kit , Diabetes Complications/metabolism , Mesenchymal Stem Cells/metabolism , Cell- and Tissue-Based Therapy/methods
5.
Biogerontology ; 24(6): 957-969, 2023 12.
Article in English | MEDLINE | ID: mdl-37642806

ABSTRACT

Along with altering brain responses to stress, aging may also impair recovery from depression symptoms. In the present study, we investigated depressive-like behaviors in young and aged rats and assayed the levels of microRNA-101 (miR-101), Rac1/RhoA, PSD-95, and GluR1 in the prefrontal cortex (PFC) after stress cessation and after a recovery period. Young (3 months old) and aged (22 months old) male Wistar rats were divided into six groups; Young control (YNG), young rats received chronic stress for four weeks (YNG + CS), young rats received chronic stress for four weeks followed by a 6-week recovery period (YNG + CS + REC), Aged control (AGED), aged rats received chronic stress for four weeks (AGED + CS), and aged rats received chronic stress for four weeks followed by a 6-week recovery period (AGED + CS + REC). Stress-induced depression, evaluated by the sucrose preference test (SPT) and forced swimming test (FST), was yet observed after the recovery period in aged but not in young rats, which were accompanied by unchanged levels of miR-101, Rac1/RhoA, GluR1, and PSD-95 in the PFC of aged rats. These data suggested that impaired synaptic plasticity of glutamatergic synapses via the miR-101/Rac1/RhoA pathway may contribute to the delayed behavioral recovery after stress exposure observed in aging animals.


Subject(s)
Depression , MicroRNAs , Rats , Animals , Male , Depression/metabolism , Rats, Wistar , Prefrontal Cortex/metabolism , Aging , Stress, Psychological/metabolism , Disease Models, Animal , rac1 GTP-Binding Protein/metabolism
6.
Iran J Basic Med Sci ; 26(6): 725-730, 2023.
Article in English | MEDLINE | ID: mdl-37275757

ABSTRACT

Objectives: Apoptosis is common and often comorbid with aging and stress-related mood disorders. Evidence suggests that fresh mitochondria could reverse age-related dysfunctions in organs, especially in the brain. Therefore, this study investigated the effect of young mitochondria administration on the apoptosis process in the prefrontal cortex (PFC) of aged rats exposed to chronic stress. Materials and Methods: Aged (22 months old) male rats were randomly assigned into four groups: aged control (AC), aged rats treated with young mitochondria (A+M), aged rats subjected to chronic stress for four weeks (A+St), and aged rats subjected to chronic stress and treated with young mitochondria (A+St+M). A+M and A+St+M groups received a single ICV injection (10 µl) of fresh mitochondria isolated from the brain of young rats for five minutes (2 µl/min). Finally, the levels of Malondialdehyde (MDA), Cytochrome c (Cyt c), Bax, Bcl-2, and Caspase-3 expression were investigated in the PFC. Results: Young mitochondria administration reduced neuronal apoptosis in the PFC, associated with down-regulation of MDA, Bax, and Caspase-3 and up-regulation of Bcl-2. Moreover, fresh mitochondria partially improved the chronic stress-induced mitochondrial dysfunction in aged rats, as indicated by reduced cytochrome c (Cyt c) release from the mitochondria. Conclusion: These results suggest mitotherapy could reverse cell viability and mitochondrial dysfunction-induced apoptosis in the PFC tissue of aged rats subjected to stressful stimuli.

7.
J Diabetes Metab Disord ; 22(1): 793-800, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37255788

ABSTRACT

Background: Despite the vulnerability of pulmonary tissue to diabetic conditions, there are few reports related to the detrimental effects of hyperglycemia and therapeutic modalities on lung parenchyma. Here, the apoptotic changes were monitored in the diabetic pulmonary tissue of mice (DM1) subjected to a four‒week swimming plan. Methods: The mice were randomly allocated into Control; Control + Swimming (S); Diabetic group (D); and Diabetic + Swimming (D + S) groups (each in 8 mice). In the D and D + S groups, mice received intraperitoneally 50 mg/kg of streptozotocin (STZ). After 14 days, swimming exercise was done for four weeks. The expression of il-1ß, bcl-2, bax, and caspase-3 was investigated using real-time PCR analysis. A histological examination was performed using H&E staining. Results: DM1 significantly upregulated il-1ß, bax, and caspase-3, and down-regulated bcl-2 compared to the non-diabetic mice (p < 0.05). We noted that swimming exercises reversed the expression pattern of all genes in the diabetic mice and closed to basal levels (p < 0.05). Data indicated that swimming exercise could diminish emphysematous changes, and interstitial pneumonitis induced by STZ. Along with these changes, swimming exercise had protective effects to reduce the thickness of the inter-alveolar septum and mean alveolar area in diabetic mice. Conclusion: These data demonstrated that swimming exercises could decrease DM1-related pathologies in mouse lungs by regulating apoptosis and inflammatory response.

8.
Biogerontology ; 24(2): 257-273, 2023 04.
Article in English | MEDLINE | ID: mdl-36626036

ABSTRACT

This study aimed to determine the effects of mitotherapy on learning and memory and hippocampal kynurenine (Kyn) pathway, mitochondria function, and dendritic arborization and spines density in aged rats subjected to chronic mild stress. Twenty-eight male Wistar rats (22 months old( were randomly divided into Aged, Aged + Mit, Aged + Stress, and Aged + Stress + Mit groups. Aged rats in the stress groups were subjected to different stressors for 28 days. The Aged + Mit and Aged + stress + Mit groups were treated with intracerebroventricular injection (10 µl) of fresh mitochondria harvested from the young rats' brains, and other groups received 10 µl mitochondria storage buffer. Spatial and episodic-like memories were assessed via the Barnes maze and novel object recognition tests. Indoleamine 2,3-dioxygenase (IDO) expression and activity, Kyn, Tryptophan (TRY), ATP levels, and mitochondrial membrane potential (MMP) were measured in the hippocampus region. Golgi-Cox staining was also performed to assess the dendritic branching pattern and dendritic spines in the hippocampal CA1 subfield. The results showed that mitotherapy markedly improved both spatial and episodic memories in the Aged + Stress + Mit group compared to the Aged + Stress. Moreover, mitotherapy decreased IDO protein expression and activity and Kyn levels, while it increased ATP levels and improved MMP in the hippocampus of the Aged + Stress + Mit group. Besides, mitotherapy restored dendritic atrophy and loss of spine density in the hippocampal neurons of the stress-exposed aged rats. These findings provide evidence for the therapeutic effect of mitotherapy against stress-induced cognitive deterioration in aged rats by improving hippocampal mitochondrial function and modulation of the Kyn pathway.


Subject(s)
Cognitive Dysfunction , Hippocampus , Rats , Male , Animals , Rats, Wistar , Hippocampus/metabolism , Tryptophan/metabolism , Tryptophan/pharmacology , Kynurenine/metabolism , Kynurenine/pharmacology , Adenosine Triphosphate/metabolism
9.
BMC Mol Cell Biol ; 23(1): 11, 2022 Feb 24.
Article in English | MEDLINE | ID: mdl-35209844

ABSTRACT

BACKGROUND: To circumvent some pitfalls related to acute status, chronic model of asthma is conceived to be more suitable approach to guarantee the conditions which are similar to human pulmonary disease. Here, possible therapeutic mechanisms were monitored by which c-kit+ bone marrow cells can attenuate vascular inflammation in rat model of chronic asthma. RESULTS: Data revealed c-Kit+ cells could significantly reduce pathological injures in asthmatic rats via modulating the expression of IL-4, INF-γ, ICAM-1 and VCAM-1 in lung tissues and TNF-α, IL-1ß and NO levels in BALF (p < 0.001 to p < 0.05). Besides, c-Kit+ cells reduced increased levels of VCAM-1 evaluated by immunohistochemistry staining. In contrast to c-Kit+ cells, c-Kit- cells could not exert beneficial effects in the asthmatic conditions. CONCLUSION: Overall, we found that systemic administration of C-kit positive cells can diminish pulmonary and vascular inflammation of chronic asthmatic changes in a rat model. These cells are eligible to suppress inflammation and nitrosative stress in lung tissue coincides with the reduction of pathological changes. These data indicate that C-kit positive cells be used as an alternative cell source for the amelioration of asthmatic changes.


Subject(s)
Asthma , Animals , Asthma/drug therapy , Asthma/metabolism , Bone Marrow Cells/metabolism , Inflammation/metabolism , Lung/metabolism , Lung/pathology , Proto-Oncogene Proteins c-kit/metabolism , Rats
10.
Mech Ageing Dev ; 202: 111632, 2022 03.
Article in English | MEDLINE | ID: mdl-35065970

ABSTRACT

Impaired mitochondrial function and abnormalities in the tryptophan (Trp)-kynurenine (Kyn) pathway are linked to age-related mood disorders. This study investigated the effect of intracerebroventricular (ICV) injection of the mitochondria isolated from young rat brain on depression-like behaviors of aged rats subjected to chronic mild stress (CMS). Aged (22 months old) male rats were randomly assigned into four groups: Aged, Aged + Mit, Aged + CMS, and Aged + CMS + Mit. Anxiety- and depression-like behaviors were assessed using elevated plus maze (EPM), open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT). Mitochondrial membrane potential (MMP), ATP levels, indoleamine 2, 3-dioxygenase (IDO) levels, and Kyn metabolites were measured in the prefrontal cortex (PFC). Golgi Cox staining was used to investigate the neuronal morphology. Mitotherapy decreased immobility time and anhedonia in the FST; increased open arm time and entries in the EPM; decreased grooming and increased rearing, center time, and the entrance in the OFT. Mitotherapy also reduced IDO and Kyn metabolites, restored MMP and ATP production, and enhanced dendritic length and spine density in the PFC. Overall, mitotherapy improved anxiety-and depression-like behaviors in aged rats and it could be considered as a new therapeutic strategy for age-related depressive disorders.


Subject(s)
Behavior, Animal , Depression , Animals , Anxiety/metabolism , Behavior, Animal/physiology , Depression/metabolism , Depression/therapy , Disease Models, Animal , Hippocampus/metabolism , Male , Mitochondria , Rats
11.
Neurochem Res ; 47(2): 358-371, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34626305

ABSTRACT

Pathophysiology of depression in elderlies is linked to aging-associated increase in indoleamine 2,3-dioxygenase (IDO) levels and activity and kynurenine (Kyn) metabolites. Moreover, these aging-induced changes may alter the brain's responses to stress. Growing evidence suggested that young plasma can positively affect brain dysfunctions in old age. The present study aimed to investigate whether the antidepressant effects of young plasma administration in aged rats subjected to chronic unpredictable mild stress (CUMS) and underlying mechanisms, focusing on the prefrontal cortex (PFC). Young (3 months old) and aged (22 months old) male rats were divided into five groups; young control, aged control, aged rats subjected to CUMS (A + CUMS), aged rats subjected to CUMS and treated with young plasma (A + CUMS + YP), and aged rats subjected to CUMS and treated with old plasma (A + CUMS + OP). Plasma was injected (1 ml, intravenously) three times per week for four weeks. Young plasma significantly improved CUMS-induced depressive-like behaviors, evidenced by the increased sucrose consumption ratio in the sucrose preference test and the reduced immobility time in the forced swimming test. Furthermore, young plasma markedly reduced the levels of interferon-gamma (IFN-γ), IDO, Kyn, and Kyn to tryptophan (Kyn/Trp) ratio in PFC tissue. Expression levels of the serotonin transporter and growth-associated protein (GAP)-43 were also significantly increased after chronic administration of young plasma. These findings provide evidence for the antidepressant effect of young plasma in old age; however, whether it improves depressive behaviors or faster recovery from stress-induced deficits is required to be elucidated.


Subject(s)
Indoleamine-Pyrrole 2,3,-Dioxygenase , Kynurenine , Animals , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Depression/metabolism , Disease Models, Animal , Hippocampus/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Kynurenine/metabolism , Male , Prefrontal Cortex/metabolism , Rats , Stress, Psychological/metabolism
12.
Exp Physiol ; 106(7): 1621-1630, 2021 07.
Article in English | MEDLINE | ID: mdl-34018261

ABSTRACT

NEW FINDINGS: What is the central question of this study? Young plasma contains several rejuvenating factors that exert beneficial effects in ageing and neurodegenerative diseases: can repeated transfusion of young plasma improve depressive behaviour in aged rats? What is the main finding and its importance? Following chronic transfusion of young plasma, depressive behaviour was improved in the depression model of aged rats, which was associated with reduced apoptosis process in the prefrontal cortex. ABSTRACT: Brain ageing alters brain responses to stress, playing an essential role in the pathophysiology of late-life depression. Moreover, apoptotic activity is up-regulated in the prefrontal cortex in ageing and stress-related mood disorders. Considerable evidence suggests that factors in young blood could reverse age-related dysfunctions in organs, especially in the brain. Therefore, this study investigated the effect of young plasma administration on depressive behaviours in aged rats exposed to chronic unpredictable mild stress (CUMS), with a focus on the apoptosis process. Young (3 months old) and aged (22 months old) male rats were randomly assigned into four groups: young control (YC), aged control (AC), aged rats subjected to CUMS (A+CUMS) and aged rats subjected to CUMS and treated with young plasma (A+CUMS+YP). In the A+CUMS and A+CUMS+YP groups, CUMS was used to generate the depression rat model. Moreover, the A+CUMS+YP group received pooled plasma (1 ml, intravenously), collected from young rats, three times per week for 4 weeks. Young plasma administration significantly improved CUMS-induced depression-like behaviours, including decreased sucrose consumption ratio, reduced locomotor activity and prolonged immobility time. Importantly, young plasma reduced neuronal apoptosis in the prefrontal cortex that was associated with reduced TUNEL-positive cells and cleaved caspase-3 protein levels in the A+CUMS+YP compared with the A+CUMS group. Young plasma can partially improve the neuropathology of late-life depression through the apoptotic signalling pathways.


Subject(s)
Antidepressive Agents , Depression , Animals , Antidepressive Agents/pharmacology , Apoptosis , Depression/metabolism , Depression/therapy , Disease Models, Animal , Hippocampus , Male , Prefrontal Cortex/metabolism , Rats , Stress, Psychological/metabolism
13.
Avicenna J Phytomed ; 8(2): 152-160, 2018.
Article in English | MEDLINE | ID: mdl-29632846

ABSTRACT

OBJECTIVE: Diabetes is associated with vascular complications and impaired angiogenesis. Since angiogenesis plays a crucial role in vascular homeostasis in ischemic heart diseases, in this study, the effect of IMOD™ on miR-503 and CDC25 expression level which are altered in impaired angiogenesis were investigated in heart tissue of diabetic rats. MATERIALS AND METHODS: Forty male Wistar rats (200-250 g) were randomly classified into 4 groups: control (C), IMOD™ (I), diabetes (D), and diabetes+IMOD™ (D+I). For induction of experimental diabetes in animals, a single dose of streptozotocin (STZ; 60mg/kg) was injected intraperitoneally. After 8 weeks of treatment with IMOD™ (20 mg/kg/day), heart tissue samples were removed and used for measurement of miR-503 and CDC25 expression level as well as histological studies. RESULTS: Results of this study showed that diabetes decreased heart tissue angiogenesis which was associated with increased miR-503 and reduced CDC25 expression levels (p<0.05) and IMOD™ could reduce the expression of miR-503 and increase the expression of CDC25 (p<0.05). Moreover, IMOD™ extensively induced angiogenesis in the heart tissue of diabetic group. However, IMOD™ had no significant effect on expressions of miR-503 and CDC25, or angiogenesis in healthy rats. CONCLUSION: This study showed that IMOD™ is able to increase angiogenesis in the heart tissue of diabetic rats. The angiogenic effect of IMOD™ is associated with reduction of miR-503 expression and increased expression of CDC25.

14.
Endocr Regul ; 52(1): 1-5, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-29453920

ABSTRACT

OBJECTIVE: Trans-chalcone is a chalcone with hepatoprotective and anti-inflammatory effects. However, the mechanism of these positive effects, especially on miR-451 as an inflammatory regulator, is poorly understood. In this regard, this microRNA (miRNA) acts by inhibition of hepatic interleukin-8 (IL-8) production in the liver which is one of the main proinflammatory cytokines. Th is study for the first time examined the effect of trans-chalcone on miR-451/IL-8 pathway. METHODS: In present study, 21 male rats were randomly divided into 3 groups (n=7 per each group): control which received solvent (NS), groups 2 (N2T) and 3 (N6T), which received transchalcone for 2 and 6 weeks, respectively. Hepatic level of miR-451 was measured by qRT-PCR. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as hepatic level of IL-8 protein were measured. RESULTS: Trans-chalcone decreased hepatic level of IL-8 protein and serum level of ALT aft er 2 weeks of treatment without significant change in hepatic miR-451. Moreover, it increased hepatic level of miR-451 and reduced hepatic IL-8 as well as AST and ALT aft er 6 weeks. CONCLUSION: Based on the results of present study, miR-451/IL-8 pathway is a possible mechanism for hepatoprotective action of trans-chalcone in long-term.


Subject(s)
Chalcone/pharmacology , Interleukin-8/drug effects , Liver/drug effects , Liver/metabolism , MicroRNAs/drug effects , Alanine Transaminase/blood , Alanine Transaminase/drug effects , Animals , Aspartate Aminotransferases/blood , Aspartate Aminotransferases/drug effects , Chalcone/administration & dosage , Male , Random Allocation , Rats , Rats, Wistar
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