Retraction notice to “Noopept; a nootropic dipeptide, modulates persistent inflammation by effecting spinal microglia dependent Brain Derived Neurotropic Factor (BDNF) and pro-BDNF expression throughout apoptotic process” [Heliyon (2021) e06219]

Objective: Depression and diabetes are closely associated in a reciprocal manner, leading to significant morbidity and mortality with an evidence of a pro-inflammatory state underlying pathophysiology of both diseases. Unfortunately, little information is available about the effects of antidepressant drugs on hippocampal brain-derived neurotrophic factor (BDNF) and toll-like receptor-4 (TLR-4) expression in diabetes.Methods: We investigated the effect of chronic administration of fluoxetine (FLU) and imipramine (IMIP) on behavioral, metabolic, and inflammatory abnormalities in diabetic and non-diabetic rats exposed to chronic restraint stress (CRS).Results: Both diabetes and CRS induced depressive-like behavior which was more prominent in diabetic/depressed rats; this was reversed by chronic treatment with FLU and IMIP. Diabetic and non-diabetic rats exposed to CRS showed a significant increase in hippocampal expression of TLR-4 and pro-inflammatory cytokines alongside a decrease in BDNF expression. FLU and IMIP ameliorated these inflammatory abnormalities.Conclusion: Diabetes mellitus (DM) and chronic stress induced a depressive-like behavior associated with an increase in hippocampal expression of TLR-4, tumor necrosis factor-α, and interleukin-1ß with a significant correlation to decreased BDNF expression. FLU and IMIP showed comparable effects regards the improvement of depressive and inflammatory abnormalities associated with DM.

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Electrically evoked local muscle contractions cause an increase in hippocampal BDNF

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2017-0536 ◽

2018 ◽

Vol 43 (5) ◽

pp. 491-496 ◽

Cited By ~ 5

Author(s):

Takahiro Maekawa ◽

Riki Ogasawara ◽

Arata Tsutaki ◽

Kihyuk Lee ◽

Satoshi Nakada ◽

...

Keyword(s):

Muscle Contractions ◽

Triceps Surae ◽

Sprague Dawley ◽

Bdnf Expression ◽

Custom Made ◽

Fibronectin Type Iii ◽

Systemic Factors ◽

Triceps Surae Muscles ◽

Neurotropic Factor ◽

Fibronectin Type Iii Domain

High-intensity exercise has recently been shown to cause an increase in brain-derived neurotropic factor (BDNF) in the hippocampus. Some studies have suggested that myokines secreted from contracting skeletal muscle, such as irisin (one of the truncated form of fibronectin type III domain-containing protein 5 (FNDC5)), play important roles in this process. Thus, we hypothesized that locally evoked muscle contractions may cause an increase of BDNF in the hippocampus through some afferent mechanisms. Under anesthesia, Sprague–Dawley rats were fixed on a custom-made dynamometer and their triceps surae muscles were made to maximally contract via delivery of electric stimulations of the sciatic nerve (100 Hz with 1-ms pulse and 3-s duration). Following 50 repeated maximal isometric contractions, the protein expressions of BDNF and activation of its receptor in the hippocampus significantly increased compared with the sham-operated control rats. However, the expression of both BDNF and FNDC5 within stimulated muscles did not significantly increase, nor did their serum concentrations change. These results indicate that local muscular contractions under unconsciousness can induce BDNF expression in the hippocampus. This effect may be mediated by peripheral reception of muscle contraction, but not by systemic factors.

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Centella asiaticaPrevents Increase of Hippocampal Tumor Necrosis Factor-αIndependently of Its Effect on Brain-Derived Neurotrophic Factor in Rat Model of Chronic Stress

BioMed Research International ◽

10.1155/2019/2649281 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Mawaddah Ar Rochmah ◽

Ika Murti Harini ◽

Dian Eurike Septyaningtrias ◽

Dwi Cahyani Ratna Sari ◽

Rina Susilowati

Keyword(s):

Chronic Stress ◽

Neuroprotective Effect ◽

Centella Asiatica ◽

Sirtuin 1 ◽

Male Rats ◽

Enzyme Linked Immunosorbent Assay ◽

Sprague Dawley ◽

Bdnf Expression ◽

Neurotropic Factor ◽

The Relationship

Centella asiaticaameliorates memory impairment and induces expression of hippocampal brain-derived neurotropic factor (BDNF) in chronically stressed rats. The relationship between the anti-inflammatory effect ofCentella asiaticaon hippocampal BDNF and the involvement of sirtuin-1, a BDNF expression regulator, in neuroprotective mechanisms ofCentella asiaticawarrants an investigation. We investigated the effect ofCentella asiaticaethanolic extracts (CA) on TNF-α, IL-10, and SIRT1 levels and whether these predicted BDNF expression in rat hippocampus after chronic stress. For the experiments, thirty male rats (Sprague Dawley) were divided into six groups: nonstressed-control, stressed-control, nonstressed +CA 300mg/kg/d, stressed +CA 150 mg/kg/d, stressed +CA 300 mg/kg/d, and stressed +CA 600 mg/kg/d. On day 28, rats were sacrificed and hippocampus was dissected out. Hippocampal TNF-α, IL-10, SIRT1, and BDNF were measured by enzyme-linked immunosorbent assay. Hippocampal TNF-αlevel was significantly higher in the stressed-control compared to nonstressed-control groups. Across all stress conditions, rats receiving the highest dose of CA had the lowest mean TNF-αand highest mean BDNF. There were no significant differences in IL-10 and SIRT1 levels between groups. Hippocampal TNF-αdid not predict hippocampal BDNF in a regression analysis. In conclusion, lower TNF-αand higher BDNF in the hippocampus support the hypothesis that these factors independently contribute toCentella asiatica’s neuroprotective effect in chronically stressed rats.

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Brain-derived neurotrophic factor is associated with human muscle satellite cell differentiation in response to muscle-damaging exercise

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2019-0501 ◽

2020 ◽

Vol 45 (6) ◽

pp. 581-590 ◽

Cited By ~ 1

Author(s):

Bryon R. McKay ◽

Joshua P. Nederveen ◽

Stephen A. Fortino ◽

Tim Snijders ◽

Sophie Joanisse ◽

...

Keyword(s):

Satellite Cell ◽

Time Course ◽

Muscle Satellite Cell ◽

Bdnf Expression ◽

Early Differentiation ◽

Signalling Molecules ◽

Complex Process ◽

Proliferation And Differentiation ◽

Neurotropic Factor

Muscle satellite cell (SC) regulation is a complex process involving many key signalling molecules. Recently, the neurotrophin brain-derived neurotropic factor (BDNF) has implicated in SC regulation in animals. To date, little is known regarding the role of BDNF in human SC function in vivo. Twenty-nine males (age, 21 ± 0.5 years) participated in the study. Muscle biopsies from the thigh were obtained prior to a bout of 300 maximal eccentric contractions (Pre), and at 6 h, 24 h, 72 h, and 96 h postexercise. BDNF was not detected in any quiescent (Pax7+/MyoD−) SCs across the time-course. BDNF colocalized to 39% ± 5% of proliferating (Pax7+/MyoD+) cells at Pre, which increased to 84% ± 3% by 96 h (P < 0.05). BDNF was only detected in 13% ± 5% of differentiating (Pax7−/MyoD+) cells at Pre, which increased to 67% ± 4% by 96 h (P < 0.05). The number of myogenin+ cells increased 95% from Pre (1.6 ± 0.2 cells/100 myofibres (MF)) at 24 h (3.1 ± 0.3 cells/100 MF) and remained elevated until 96 h (cells/100 MF), P < 0.05. The proportion of BDNF+/myogenin+ cells was 26% ± 0.3% at Pre, peaking at 24 h (49% ± 3%, P < 0.05) and remained elevated at 96 h (P < 0.05). These data are the first to demonstrate an association between SC proliferation and differentiation and BDNF expression in humans in vivo, with BDNF colocalization to SCs increasing during the later stages of proliferation and early differentiation. Novelty BDNF is associated with SC response to muscle injury. BDNF was not detected in nonactivated (quiescent) SCs. BDNF is associated with late proliferation and early differentiation of SCs in vivo in humans.

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Adverse Maternal Environment Alters MicroRNA-10b-5p Expression and Its Epigenetic Profile Concurrently with Impaired Hippocampal Neurogenesis in Male Mouse Hippocampus

Developmental Neuroscience ◽

10.1159/000515750 ◽

2021 ◽

pp. 1-11

Author(s):

Xingrao Ke ◽

Yingliu Huang ◽

Qi Fu ◽

Robert H. Lane ◽

Amber Majnik

Keyword(s):

Hippocampal Neurogenesis ◽

Bdnf Expression ◽

Maternal Environment ◽

Neuronal Marker ◽

Protein Levels ◽

Epigenetic Profile ◽

Mouse Hippocampus ◽

Differentiation Marker ◽

Underlying Mechanisms ◽

Neurotropic Factor

An adverse maternal environment (AME) predisposes adult offspring toward cognitive impairment in humans and mice. However, the underlying mechanisms remain poorly understood. Epigenetic changes in response to environmental exposure may be critical drivers of this change. Epigenetic regulators, including microRNAs, have been shown to affect cognitive function by altering hippocampal neurogenesis which is regulated in part by brain-derived neurotropic factor (BDNF). We sought to investigate the effects of AME on miR profile and their epigenetic characteristics, as well as neurogenesis and BDNF expression in mouse hippocampus. Using our mouse model of AME which is composed of maternal Western diet and prenatal environmental stress, we found that AME significantly increased hippocampal miR-10b-5p levels. We also found that AME significantly decreased DNA methylation and increased accumulations of active histone marks H3 lysine (K) 4me3, H3K14ac, and H3K36me3 at miR-10b promoter. Furthermore, AME significantly decreased hippocampal neurogenesis by decreasing cell numbers of Ki67+ (proliferation marker), NeuroD1+ (neuronal differentiation marker), and NeuN+ (mature neuronal marker) in the dentate gyrus (DG) region concurrently with decreased hippocampal BDNF protein levels. We speculate that the changes in epigenetic profile at miR-10b promoter may contribute to upregulation of miR-10b-5p and subsequently lead to decreased BDNF levels in a model of impaired offspring hippocampal neurogenesis and cognition in mice.

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Nootropic dipeptide, Noopept can modulate hyperalgesia by effecting on spinal microglia dependent Brain Derived Neurotropic Factor (BDNF) and pro-BDNF expression and apoptosis during persistent inflammation

10.21203/rs.2.21124/v1 ◽

2020 ◽

Author(s):

Mona Taghizadeh ◽

Nader Maghsoudi ◽

Homa Manaheji ◽

Valery Akparov ◽

Mansoureh Baniasadi ◽

...

Keyword(s):

Acute Phase ◽

Cell Apoptosis ◽

Thermal Hyperalgesia ◽

Chronic Phase ◽

Pain Behavior ◽

Peripheral Inflammation ◽

Bdnf Expression ◽

Study Results ◽

Neurotropic Factor ◽

Apoptosis Process

Abstract Background: There are largely unknown associations between changes in pain behavior responses during persistent peripheral inflammation and spinal cell alteration such as apoptosis. Some evidence suggests that microglia and microglia related mediators play notable roles in induction and maintenance of central nervous system pathologies and inflammatory pain. By considering those relationships and microglia related nootrophic factors, such as the Brain Derived Neurotrophic Factor (BDNF) in CNS, we attempted to assess the relationship between microglia dependent BDNF and its precursor with pain behavior through spinal cell apoptosis as well as the effect of Noopept on this relationship. Methods: Persistent peripheral inflammation was induced by a single subcutaneous injection of Complete Freund’s Adjuvant (CFA) on day 0. Thermal hyperalgesia, paw edema, microglial activity, microglia dependent BDNF, pro-BDNF expression, and apoptosis were assessed in different experimental groups by confirmed behavioral and molecular methods on days 0, 7, and 21 of the study. Results: Our findings revealed hyperalgesia and spinal cell apoptosis significantly increased during the acute phase of CFA-induced inflammation but was then followed by a decrement in the chronic phase of the study. Aligned with these variations in spinal microglial activity, microglia dependent BDNF significantly increased during the acute phase of CFA-induced inflammation. Our results also indicated that daily administration of Noopept (during 21 days of the study) not only caused a significant decrease in hyperalgesia and microglia dependent BDNF expression but also changed the apoptosis process in relation to microglia activity alteration. Conclusions: It appears that the administration of Noopept can decrease spinal cell apoptosis and hyperalgesia during CFA-induced inflammation due to its direct effects on microglial activity and microglia dependent BDNF and pro-BDNF expression.

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Neural Mobilization Treatment Decreases Glial Cells and Brain-Derived Neurotrophic Factor Expression in the Central Nervous System in Rats with Neuropathic Pain Induced by CCI in Rats

Pain Research and Management ◽

10.1155/2017/7429761 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Aline Carolina Giardini ◽

Fabio Martinez dos Santos ◽

Joyce Teixeira da Silva ◽

Mara Evany de Oliveira ◽

Daniel Oliveira Martins ◽

...

Keyword(s):

Chronic Pain ◽

Neuropathic Pain ◽

Glial Cells ◽

Microglial Cell ◽

Control Group ◽

Bdnf Expression ◽

Nociceptive Transmission ◽

The Central Nervous System ◽

Neurotropic Factor ◽

Ventral Posterolateral Nucleus

Background. Glial cells are implicated in the development of chronic pain and brain-derived neurotropic factor (BDNF) released from activated microglia contributes to the nociceptive transmission. Neural mobilization (NM) technique is a method clinically effective in reducing pain sensitivity. Here we examined the involvement of glial cells and BDNF expression in the thalamus and midbrain after NM treatment in rats with chronic constriction injury (CCI). CCI was induced and rats were subsequently submitted to 10 sessions of NM, every other day, beginning 14 days after CCI. Thalamus and midbrain were analyzed for glial fibrillary acidic protein (GFAP), microglial cell OX-42, and BDNF using Immunohistochemistry and Western blot assays.Results. Thalamus and midbrain of CCI group showed increases in GFAP, OX-42, and BDNF expression compared with control group and, in contrast, showed decreases in GFAP, OX-42, and BDNF after NM when compared with CCI group. The decreased immunoreactivity for GFAP, OX-42, and BDNF in ventral posterolateral nucleus in thalamus and the periaqueductal gray in midbrain was shown by immunohistochemistry.Conclusions. These findings may improve the knowledge about the involvement of astrocytes, microglia, and BDNF in the chronic pain and show that NM treatment, which alleviates neuropathic pain, affects glial cells and BDNF expression.

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BIOCHEMICAL STUDIES OF HIPPOCAMPAL GENE EXPRESSION OF BRAIN-DERIVED NEUROTROPIC FACTOR AND TOLL-LIKE RECEPTOR-4 IN DIABETIC RATS EXPOSED TO CHRONIC STRESS: EFFECTS OF ANTIDEPRESSANT DRUGS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i1.21593 ◽

2018 ◽

Vol 11 (1) ◽

pp. 271

Author(s):

Sawsan Aboul-fotouh ◽

Doaa Mohamed Hassan ◽

Mohamed Zaki Eldeen Habib ◽

Ahmed Ibrahim Amin ◽

Samar K. Kassim ◽

...

Keyword(s):

Chronic Stress ◽

Antidepressant Drugs ◽

Chronic Administration ◽

Diabetic Rats ◽

Toll Like Receptor ◽

Bdnf Expression ◽

Toll Like Receptor 4 ◽

Inflammatory State ◽

Neurotropic Factor ◽

Factor Α

Objective: Depression and diabetes are closely associated in a reciprocal manner, leading to significant morbidity and mortality with an evidence of a pro-inflammatory state underlying pathophysiology of both diseases. Unfortunately, little information is available about the effects of antidepressant drugs on hippocampal brain-derived neurotrophic factor (BDNF) and toll-like receptor-4 (TLR-4) expression in diabetes.Methods: We investigated the effect of chronic administration of fluoxetine (FLU) and imipramine (IMIP) on behavioral, metabolic, and inflammatory abnormalities in diabetic and non-diabetic rats exposed to chronic restraint stress (CRS).Results: Both diabetes and CRS induced depressive-like behavior which was more prominent in diabetic/depressed rats; this was reversed by chronic treatment with FLU and IMIP. Diabetic and non-diabetic rats exposed to CRS showed a significant increase in hippocampal expression of TLR-4 and pro-inflammatory cytokines alongside a decrease in BDNF expression. FLU and IMIP ameliorated these inflammatory abnormalities.Conclusion: Diabetes mellitus (DM) and chronic stress induced a depressive-like behavior associated with an increase in hippocampal expression of TLR-4, tumor necrosis factor-α, and interleukin-1ß with a significant correlation to decreased BDNF expression. FLU and IMIP showed comparable effects regards the improvement of depressive and inflammatory abnormalities associated with DM.

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DW2009 Elevates the Efficacy of Donepezil against Cognitive Impairment in Mice

Nutrients ◽

10.3390/nu13093273 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3273

Author(s):

Dong-Yun Lee ◽

Jeon-Kyung Kim ◽

Soo-Won Yun ◽

Myung Joo Han ◽

Dong-Hyun Kim

Keyword(s):

Cognitive Impairment ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Acetylcholinesterase Inhibitor ◽

Bdnf Expression ◽

Neurotropic Factor ◽

Factor Α ◽

The Brain ◽

Necrosis Factor

Lactobacillus plantarum C29 and DW2009 (C29-fermented soybean) alleviate cognitive impairment through the modulation of the microbiota-gut-brain axis. Therefore, we examined whether combining donepezil, a well-known acetylcholinesterase inhibitor, with C29 or DW2009 could synergistically alleviate cognitive impairment in mice. Oral administration of donepezil combined with or without C29 (DC) or DW2009 (DD) alleviated lipopolysaccharide (LPS)-induced cognitive impairment-like behaviors more strongly than treatment with each one alone. Their treatments significantly suppressed the NF-κB+/Iba1+ (activated microglia) population, NF-κB activation, and tumor necrosis factor-α and interleukin-1β expression in the hippocampus, while the brain-derived neurotropic factor (BDNF)+/NeuN+ cell population and BDNF expression increased. Their treatments strongly suppressed LPS-induced colitis. Moreover, they increased the Firmicutes population and decreased the Cyanobacteria population in gut microbiota. Of these, DD most strongly alleviated cognitive impairment, followed by DC. In conclusion, DW2009 may synergistically or additively increase the effect of donepezil against cognitive impairment and colitis by regulating NF-κB-mediated BDNF expression.

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