scholarly journals Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Sherry L. Xu ◽  
Cathy W. C. Bi ◽  
Roy C. Y. Choi ◽  
Kevin Y. Zhu ◽  
Abudureyimu Miernisha ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Food Supplement ◽  
Brain Diseases ◽  
Health Food ◽  
Beneficial Effects ◽  
Highly Active ◽  
Rat Astrocytes ◽  
The Brain

Neurotrophic factors are playing vital roles in survival, growth, and function of neurons. Regulation of neurotrophic factors in the brain has been considered as one of the targets in developing drug or therapy against neuronal disorders. Flavonoids, a family of multifunctional natural compounds, are well known for their neuronal beneficial effects. Here, the effects of flavonoids on regulating neurotrophic factors were analyzed in cultured rat astrocytes. Astrocyte is a major secreting source of neurotrophic factors in the brain. Thirty-three flavonoids were screened in the cultures, and calycosin, isorhamnetin, luteolin, and genistein were identified to be highly active in inducing the synthesis and secretion of neurotrophic factors, including nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF). The inductions were in time- and dose-dependent manners. In cultured astrocytes, the phosphorylation of estrogen receptor was triggered by application of flavonoids. The phosphorylation was blocked by an inhibitor of estrogen receptor, which in parallel reduced the flavonoid-induced expression of neurotrophic factors. The results proposed the role of flavonoids in protecting brain diseases, and therefore these flavonoids could be developed for health food supplement for patients suffering from neurodegenerative diseases.

scholarly journals Interplay of Good Bacteria and Central Nervous System: Cognitive Aspects and Mechanistic Considerations

2021 ◽  
Vol 15 ◽  
Author(s):  
Mahmoud Salami
Keyword(s):  
Gut Microbiota ◽  
Cognitive Processing ◽  
Clinical Problem ◽  
The Body ◽  
Brain Diseases ◽  
Normal Brain ◽  
Beneficial Effects ◽  
Normal Brain Function ◽  
The Brain ◽  
Common Clinical Problem

The human gastrointestinal tract hosts trillions of microorganisms that is called “gut microbiota.” The gut microbiota is involved in a wide variety of physiological features and functions of the body. Thus, it is not surprising that any damage to the gut microbiota is associated with disorders in different body systems. Probiotics, defined as living microorganisms with health benefits for the host, can support or restore the composition of the gut microbiota. Numerous investigations have proved a relationship between the gut microbiota with normal brain function as well as many brain diseases, in which cognitive dysfunction is a common clinical problem. On the other hand, increasing evidence suggests that the existence of a healthy gut microbiota is crucial for normal cognitive processing. In this regard, interplay of the gut microbiota and cognition has been under focus of recent researches. In the present paper, I review findings of the studies considering beneficial effects of either gut microbiota or probiotic bacteria on the brain cognitive function in the healthy and disease statuses.

scholarly journals Viral vector delivery of neurotrophic factors for Parkinson's disease therapy

2015 ◽  
Vol 17 ◽  
Author(s):  
Martin J. Kelly ◽  
Gerard W. O'Keeffe ◽  
Aideen M. Sullivan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Viral Vectors ◽  
Viral Vector ◽  
Neurodegenerative Disorder ◽  
The Brain

Parkinson's disease (PD) is a neurodegenerative disorder characterised by the progressive loss of midbrain dopaminergic neurons, which causes motor impairments. Current treatments involve dopamine replacement to address the disease symptoms rather than its cause. Factors that promote the survival of dopaminergic neurons have been proposed as novel therapies for PD. Several dopaminergic neurotrophic factors (NTFs) have been examined for their ability to protect and/or restore degenerating dopaminergic neurons, both in animal models and in clinical trials. These include glial cell line-derived neurotrophic factor, neurturin, cerebral dopamine neurotrophic factor and growth/differentiation factor 5. Delivery of these NTFs via injection or infusion to the brain raises several practical problems. A new delivery approach for NTFs involves the use of recombinant viral vectors to enable long-term expression of these factors in brain cells. Vectors used include those based on adenoviruses, adeno-associated viruses and lentiviruses. Here we review progress to date on the potential of each of these four NTFs as novel therapeutic strategies for PD, as well as the challenges that have arisen, from pre-clinical analysis to clinical trials. We conclude by discussing recently-developed approaches to optimise the delivery of NTF-carrying viral vectors to the brain.

scholarly journals Estrogen receptor α phosphorylated at Ser216 confers inflammatory function to mouse microglia

2020 ◽  
Author(s):  
Sawako Shindo ◽  
Shih-Heng Chen ◽  
Saki Gotoh ◽  
Kosuke Yokobori ◽  
Hao Hu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Inflammatory Cytokines ◽  
Estrogen Receptor Α ◽  
Brain Diseases ◽  
Antibody Array ◽  
Mouse Uterus ◽  
Glia Cells ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
The Brain

Abstract Background Estrogen receptor α (ERα) has been suggested to regulate anti-inflammatory signaling in brain microglia, the only resident immune cells in the brain. ERα conserves the phosphorylation motif at Ser216 within the DNA binding domain. Previously, Ser216 was found to be phosphorylated in neutrophils infiltrating into the mouse uterus and to enable ERα to regulate migration. Given the implication of this phosphorylation in immune regulation, ERα was examined in mouse microglia to determine if Ser216 is phosphorylated and regulates microglia’s inflammation. It was found that Ser216 was constitutively phosphorylated in microglia and demonstrated that in the absence of phosphorylated ERα in ERα KI brains microglia inflamed, confirming that phosphorylation confers ERα with anti-inflammatory capability. ERα KI mice were obese and weakened motor ability. Methods Mixed glia cells were prepared from brains of 2-days-old neonates and cultured to mature and isolate microglia. An antibody against an anti-phospho-S216 peptide of ERα (αP-S216) was used to detect phosphorylated ERα in double immunofluorescence staining with ERα antibodies and a microglia maker Iba-1 antibody. A knock-in (KI) mouse line bearing the phosphorylation-blocked ERα S216A mutation (ERα KI) was generated to examine inflammation-regulating functions of phosphorylated ERα in microglia. RT-PCR, antibody array, ELISA and FACS assays were employed to measure expressions of pro- or anti-inflammatory cytokines at their mRNA and protein levels. Rotarod tests were performed to examine motor connection ability.Results Double immune staining of mixed glia cells showed that ERα is phosphorylated at Ser216 in microglia, but not astrocytes. Immunohistochemistry with an anti-Iba-1 antibody showed that microglia cells were swollen and shortened branches in the substantial nigra (SN) of ERα KI brains, indicating the spontaneous activation of microglia as observed with those of lipopolysaccharide (LPS)-treated ERα WT brains. Pro-inflammatory cytokines were up-regulated in the brain of ERα KI brains as well as cultured microglia, whereas anti-inflammatory cytokines were down-regulated. FACS analysis showed that the number of IL-6 producing and apoptotic microglia increased in those prepared from ERα KI brains. Times of ERα KI mice on rod were shortened in Rotarod tests. Conclusions Blocking of Ser216 phosphorylation aggravated microglia activation and inflammation of mouse brain, thus confirming that phosphorylated ERα exerts anti-inflammatory functions. ERα KI mice enable us to further investigate the mechanism by which phosphorylated ERα regulates brain immunity and inflammation and brain diseases.

Neurotrophic factors and the pathophysiology of schizophrenic psychoses

2004 ◽  
Vol 19 (6) ◽  
pp. 326-337 ◽  
Author(s):  
Nuria Durany ◽  
Johannes Thome
Keyword(s):  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Treatment Strategies ◽  
Extensive Literature ◽  
National Library ◽  
Gene Level ◽  
Schizophrenic Patients ◽  
Conceptual Paper ◽  
New Treatment ◽  
The Brain

AbstractThe aim of this review is to summarize the present state of findings on altered neurotrophic factor levels in schizophrenic psychoses, on variations in genes coding for neurotrophic factors, and on the effect of antipsychotic drugs on the expression level of neurotrophic factors. This is a conceptual paper that aims to establish the link between the neuromaldevelopment theory of schizophrenia and neurotrophic factors. An extensive literature review has been done using the Pub Med database, a service of the National Library of Medicine, which includes over 14 million citations for biomedical articles back to the 1950s. The majority of studies discussed in this review support the notion of alterations of neurotrophic factors at the protein and gene level, respectively, and support the hypothesis that these alterations could, at least partially, explain some of the morphological, cytoarchitectural and neurobiochemical abnormalities found in the brain of schizophrenic patients. However, the results are not always conclusive and the clinical significance of these alterations is not fully understood. It is, thus, important to further neurotrophic factor research in order to better understand the etiopathogenesis of schizophrenic psychoses and, thus, potentially develop new treatment strategies urgently needed for patients suffering from these devastating disorders.

scholarly journals Curcumin’s Nanomedicine Formulations for Therapeutic Application in Neurological Diseases

2020 ◽  
Vol 9 (2) ◽  
pp. 430 ◽  
Author(s):  
Bahare Salehi ◽  
Daniela Calina ◽  
Anca Docea ◽  
Niranjan Koirala ◽  
Sushant Aryal ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Neurological Diseases ◽  
Amyloid Β ◽  
Brain Diseases ◽  
Metal Chelation ◽  
Brain Health ◽  
Control Center ◽  
Beneficial Effects ◽  
Different Types ◽  
The Brain

The brain is the body’s control center, so when a disease affects it, the outcomes are devastating. Alzheimer’s and Parkinson’s disease, and multiple sclerosis are brain diseases that cause a large number of human deaths worldwide. Curcumin has demonstrated beneficial effects on brain health through several mechanisms such as antioxidant, amyloid β-binding, anti-inflammatory, tau inhibition, metal chelation, neurogenesis activity, and synaptogenesis promotion. The therapeutic limitation of curcumin is its bioavailability, and to address this problem, new nanoformulations are being developed. The present review aims to summarize the general bioactivity of curcumin in neurological disorders, how functional molecules are extracted, and the different types of nanoformulations available.

scholarly journals Low-intensity pulsed ultrasound improves behavioral functions and alleviates neuroinflammation in a rat model of Parkinson’s disease

2020 ◽  
Author(s):  
Feng-Yi Yang ◽  
Chen-Yu Sung ◽  
Pai-Kai Chiang ◽  
Che-Wen Tsai
Keyword(s):  
Rat Model ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Tissue Injury ◽  
Substantia Nigra Pars Compacta ◽  
Dopamine Level ◽  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
The Brain

Abstract BackgroundParkinson’s disease (PD) is characterized by a reduction of dopamine level in the substantia nigra pars compacta (SNpc) and striatum of the brain. Low-intensity pulsed ultrasound (LIPUS) has been demonstrated recently as a non-invasive neuromodulation tool in a number of fields. LIPUS has also been reported to improve behavioral functions in PD animal models; however, the effect of LIPUS stimulation on the neurotrophic factors and neuroinflammation has not yet been addressed.MethodsPD rat model was built by injection of 6-hydroxydopamine (6-OHDA) in two sites in the right striatum. The levels of neurotrophic factors and lipocalin-2 (LCN2)-induced neuroinflammation were quantified using a western blot. Rotational test and cylinder test were conducted biweekly for eight weeks. The safety of LIPUS was assessed using Hematoxylin and Esosin (H&E) staining and Nissl staining.ResultsWhen the 6-OHDA+LIPUS and 6-OHDA groups were compared, the locomotor function of the 6-OHDA+LIPUS rats was significantly improved. After LIPUS stimulation, the number of neurons was remarkably increased in the striatum and SNpc of lesioned rats. Unilateral LIPUS stimulation did not increase brain-derived neurotrophic factor (BDNF) in the striatum and SNpc of lesioned rats. In contrast, unilateral LIPUS stimulation increased glial cell line-derived neurotrophic factor (GDNF) protein 1.98-fold unilaterally in the SNpc. Additionally, LCN2-induced neuroinflammation can be attenuated following LIPUS stimulation.ConclusionsOur data indicated that LIPUS stimulation increased GDNF and dopaminergic (DA) neuron density in the 6-OHDA-induced rat model of PD. Moreover, this technology attenuated proinflammatory mediators and reversed behavioral indicators of PD-associated motor dysfunction with no evidence of brain tissue injury. These results show that LIPUS stimulation may be a potential therapeutic tool against PD via enhancement of GDNF level and inhibition of inflammatory responses in the SNpc of the brain.

scholarly journals Neurotrophic Factors in Parkinson’s Disease: Clinical Trials, Open Challenges and Nanoparticle-Mediated Delivery to the Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Olesja Bondarenko ◽  
Mart Saarma
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Delivery Methods ◽  
Intracranial Surgery ◽  
Neuronal Populations ◽  
Pass Through ◽  
The Brain

Neurotrophic factors (NTFs) are small secreted proteins that support the development, maturation and survival of neurons. NTFs injected into the brain rescue and regenerate certain neuronal populations lost in neurodegenerative diseases, demonstrating the potential of NTFs to cure the diseases rather than simply alleviating the symptoms. NTFs (as the vast majority of molecules) do not pass through the blood–brain barrier (BBB) and therefore, are delivered directly into the brain of patients using costly and risky intracranial surgery. The delivery efficacy and poor diffusion of some NTFs inside the brain are considered the major problems behind their modest effects in clinical trials. Thus, there is a great need for NTFs to be delivered systemically thereby avoiding intracranial surgery. Nanoparticles (NPs), particles with the size dimensions of 1-100 nm, can be used to stabilize NTFs and facilitate their transport through the BBB. Several studies have shown that NTFs can be loaded into or attached onto NPs, administered systemically and transported to the brain. To improve the NP-mediated NTF delivery through the BBB, the surface of NPs can be functionalized with specific ligands such as transferrin, insulin, lactoferrin, apolipoproteins, antibodies or short peptides that will be recognized and internalized by the respective receptors on brain endothelial cells. In this review, we elaborate on the most suitable NTF delivery methods and envision “ideal” NTF for Parkinson’s disease (PD) and clinical trial thereof. We shortly summarize clinical trials of four NTFs, glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), platelet-derived growth factor (PDGF-BB), and cerebral dopamine neurotrophic factor (CDNF), that were tested in PD patients, focusing mainly on GDNF and CDNF. We summarize current possibilities of NP-mediated delivery of NTFs to the brain and discuss whether NPs have impact in improving the properties of NTFs and delivery across the BBB. Emerging delivery approaches and future directions of NTF-based nanomedicine are also discussed.

scholarly journals Brain-derived neurotrophic factor secreted by the cerebral endothelium: A new actor of brain function?

2018 ◽  
Vol 38 (6) ◽  
pp. 935-949 ◽  
Author(s):  
Christine Marie ◽  
Martin Pedard ◽  
Aurore Quirié ◽  
Anne Tessier ◽  
Philippe Garnier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neurotrophic Factor ◽  
Brain Function ◽  
Critical Role ◽  
Brain Derived Neurotrophic Factor ◽  
Brain Diseases ◽  
Cerebral Endothelium ◽  
Brain Functions ◽  
Cerebral Microvasculature ◽  
The Brain

Low cerebral levels of brain-derived neurotrophic factor (BDNF), which plays a critical role in many brain functions, have been implicated in neurodegenerative, neurological and psychiatric diseases. Thus, increasing BDNF levels in the brain is considered an attractive possibility for the prevention/treatment of various brain diseases. To date, BDNF-based therapies have largely focused on neurons. However, given the cross-talk between endothelial cells and neurons and recent evidence that BDNF expressed by the cerebral endothelium largely accounts for BDNF levels present in the brain, it is likely that BDNF-based therapies would be most effective if they also targeted the cerebral endothelium. In this review, we summarize the available knowledge about the biology and actions of BDNF derived from endothelial cells of the cerebral microvasculature and we emphasize the remaining gaps and shortcomings.

scholarly journals Extract of Fructus Cannabis Ameliorates Learning and Memory Impairment Induced by D-Galactose in an Aging Rats Model

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Ning-Yuan Chen ◽  
Cheng-Wu Liu ◽  
Wei Lin ◽  
Yi Ding ◽  
Zhang-ya Bian ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Cannabis Sativa ◽  
Folk Medicine ◽  
Underlying Mechanism ◽  
Behavioral Performance ◽  
Health Food ◽  
Once Daily ◽  
Aging Rats ◽  
Beneficial Effects ◽  
The Brain

Hempseed (Cannabis sativaL.) has been used as a health food and folk medicine in China for centuries. In the present study, we sought to define the underlying mechanism by which the extract of Fructus Cannabis (EFC) protects against memory impairment induced by D-galactose in rats. To accelerate aging and induce memory impairment in rats, D-galactose (400 mg/kg) was injected intraperitoneally once daily for 14 weeks. EFC (200 and 400 mg/kg) was simultaneously administered intragastrically once daily in an attempt to slow the aging process. We found that EFC significantly increased the activity of superoxide dismutase, while lowering levels of malondialdehyde in the hippocampus. Moreover, EFC dramatically elevated the organ indices of some organs, including the heart, the liver, the thymus, and the spleen. In addition, EFC improved the behavioral performance of rats treated with D-galactose in the Morris water maze. Furthermore, EFC inhibited the activation of astrocytes and remarkably attenuated phosphorylated tau and suppressed the expression of presenilin 1 in the brain of D-galactose-treated rats. These findings suggested that EFC exhibits beneficial effects on the cognition of aging rats probably by enhancing antioxidant capacity and anti-neuroinflammation, improving immune function, and modulating tau phosphorylation and presenilin expression.

Will caloric restriction and folate protect against AD and PD?

Neurology ◽  
2003 ◽  
Vol 60 (4) ◽  
pp. 690-695 ◽  
Author(s):  
Mark P. Mattson
Keyword(s):  
Folic Acid ◽  
Dietary Restriction ◽  
Neurodegenerative Disorders ◽  
Neurotrophic Factors ◽  
Animal Studies ◽  
Neuronal Damage ◽  
Epidemiologic Studies ◽  
Beneficial Effects ◽  
The Brain ◽  
High Calorie

Recent epidemiologic studies of different sample populations have suggested that the risk of AD and PD may be increased in individuals with high-calorie diets and in those with increased homocysteine levels. Dietary restriction and supplementation with folic acid can reduce neuronal damage and improve behavioral outcome in mouse models of AD and PD. Animal studies have shown that the beneficial effects of dietary restriction result, in part, from increased production of neurotrophic factors and cytoprotective protein chaperones in neurons. By keeping homocysteine levels low, folic acid can protect cerebral vessels and can prevent the accumulation of DNA damage in neurons caused by oxidative stress and facilitated by homocysteine. Although further studies are required in humans, the emerging data suggest that high-calorie diets and elevated homocysteine levels may render the brain vulnerable to neurodegenerative disorders.

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