scholarly journals Neuroprotective Effects and Therapeutic Potential of Transcorneal Electrical Stimulation for Depression

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2492
Author(s):  
Wing-Shan Yu ◽  
So-Hyun Kwon ◽  
Stephen Kugbere Agadagba ◽  
Leanne-Lai-Hang Chan ◽  
Kah-Hui Wong ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Therapeutic Potential ◽  
Brain Regions ◽  
Neuroprotective Effects ◽  
Transcorneal Electrical Stimulation ◽  
Beneficial Effects ◽  
Non Invasive ◽  
Antidepressant Treatments ◽  
Antidepressant Effects ◽  
Apoptosis And Inflammation

Transcorneal electrical stimulation (TES) has emerged as a non-invasive neuromodulation approach that exerts neuroprotection via diverse mechanisms, including neurotrophic, neuroplastic, anti-inflammatory, anti-apoptotic, anti-glutamatergic, and vasodilation mechanisms. Although current studies of TES have mainly focused on its applications in ophthalmology, several lines of evidence point towards its putative use in treating depression. Apart from stimulating visual-related structures and promoting visual restoration, TES has also been shown to activate brain regions that are involved in mood alterations and can induce antidepressant-like behaviour in animals. The beneficial effects of TES in depression were further supported by its shared mechanisms with FDA-approved antidepressant treatments, including its neuroprotective properties against apoptosis and inflammation, and its ability to enhance the neurotrophic expression. This article critically reviews the current findings on the neuroprotective effects of TES and provides evidence to support our hypothesis that TES possesses antidepressant effects.

scholarly journals Verapamil/Curcumin treatment attenuates the behavioral alterations observed in Williams Syndrome mice by regulation of MAPK pathway and Microglia overexpression

2021 ◽  
Author(s):  
Paula Ortiz-Romero ◽  
Gustavo Egea ◽  
Luis A Pérez-Jurado ◽  
Victoria Campuzano
Keyword(s):  
Mapk Pathway ◽  
Neurodevelopmental Disorder ◽  
Underlying Mechanism ◽  
Brain Regions ◽  
Mapk Signaling ◽  
Potential Candidate ◽  
Neuroprotective Effects ◽  
Behavioral Deficits ◽  
Activated Microglia ◽  
Beneficial Effects

AbstractWilliams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by a distinctive cognitive phenotype for which there currently are not any effective treatments. We investigated the progression of behavioral deficits present in CD (complete deletion) mice, a rodent model of WBS, after chronic treatment with curcumin, verapamil and a combination of both. These compounds have been proven to have beneficial effects over different cognitive aspects of various murine models and thus, may have neuroprotective effects in WBS. Treatment was administered orally dissolved in drinking water. A set of behavioral tests demonstrated the efficiency of combinatorial treatment. Some histological and molecular analyses were performed to analyze the effects of treatment and its underlying mechanism in CD mice. Behavioral improvement correlates with the molecular recovery of several affected pathways regarding MAPK signaling, in tight relation with the control of synaptic transmission. Moreover, CD mice showed an increased activated microglia density in different brain regions, which was prevented by treatment. Therefore, results show that treatment prevented behavioral deficits by recovering altered gene expression in cortex of CD mice, reducing activated microglia and normalizing Bdnf expression levels. These findings unravel the mechanisms underlying the beneficial effects of this novel treatment on behavioral deficits observed in CD mice, and suggest that the combination of curcumin and verapamil could be a potential candidate to treat the cognitive impairments in WBS patients.

scholarly journals Dietary Flavonoids Interaction with CREB-BDNF Pathway: An Unconventional Approach for Comprehensive Management of Epilepsy

2019 ◽  
Vol 17 (12) ◽  
pp. 1158-1175 ◽  
Author(s):  
Pallavi Sharma ◽  
Amit Kumar ◽  
Damanpreet Singh
Keyword(s):  
Therapeutic Potential ◽  
Epileptic Seizures ◽  
Brain Regions ◽  
Camp Response Element Binding ◽  
Bioactive Molecules ◽  
Comorbid Conditions ◽  
Beneficial Effects ◽  
Comprehensive Management ◽  
Dietary Flavonoids ◽  
Bdnf Pathway

cAMP response element binding protein (CREB) is a key transcriptional regulator that regulates the transcription of genes related with neuronal differentiation, synaptic plasticity, learning and memory. Brain derived neurotrophic factor (BDNF), is a CREB dependent gene which plays a pivotal role in the pathogenesis of epilepsy and central comorbid conditions associated with epilepsy. However, the beneficial or detrimental consequences of CREB-BDNF activation on the induction and/or progression of seizures depend specifically on the region of brain involved and the time of activation. The bioactive molecules that alter the activity of CREB in a way to have specialized effects in different brain regions and neural circuits involved could potentially be utilized for therapeutic purposes. Flavonoids are the polyphenolic compounds which lead to phosphorylation of CREB in the hippocampus, followed by increase in extracellular signal regulated kinase (ERK) and BDNF. Several members of flavonoid family have also showed suppression of epileptic seizures via interaction with CREB/BDNF pathway. Moreover, epilepsy is often accompanied by a number of behavioural and psychological comorbid conditions that further gets aggravated by the use of conventional antiepileptic drug therapy. Multiple studies have also supported the beneficial effects of flavonoids in cognitive and memory impairments by upregulation of CREB-BDNF pathway. The current review is an attempt to collate the available preclinical and clinical studies to establish the therapeutic potential of various dietary flavonoids in comprehensive management of epilepsy with relation to CREB-BDNF pathway.

scholarly journals Dental Mesenchymal Stem Cell Secretome: An Intriguing Approach for Neuroprotection and Neuroregeneration

2021 ◽  
Vol 23 (1) ◽  
pp. 456
Author(s):  
Agnese Gugliandolo ◽  
Emanuela Mazzon
Keyword(s):  
Stem Cells ◽  
Bioactive Molecules ◽  
Deciduous Teeth ◽  
Neuroprotective Effects ◽  
Neuronal Markers ◽  
Beneficial Effects ◽  
Non Invasive ◽  
Promote Neurite Outgrowth ◽  
Neural Crest Origin ◽  
Human Exfoliated Deciduous Teeth

Mesenchymal stem cells (MSCs) are known for their beneficial effects and regenerative potential. In particular, dental-derived MSCs have the advantage of easier accessibility and a non-invasive isolation method. Moreover, thanks to their neural crest origin, dental MSCs seem to have a more prominent neuroregenerative potential. Indeed, in basal conditions they also express neuronal markers. However, it is now well known that the beneficial actions of MSCs depend, at least in part, on their secretome, referring to all the bioactive molecules released in the conditioned medium (CM) or in extracellular vesicles (EVs). In this review we focus on the applications of the secretome derived from dental MSCs for neuroregeneration and neuroprotection. The secretomes of different dental MSCs have been tested for their effects for neuroregenerative purposes, and the secretomes of dental pulp stem cells and stem cells from human exfoliated deciduous teeth are the most studied. Both the CM and EVs obtained from dental MSCs showed that they are able to promote neurite outgrowth and neuroprotective effects. Interestingly, dental-derived MSC secretome showed stronger neuroregenerative and neuroprotective effects compared to that obtained from other MSC sources. For these reasons, the secretome obtained from dental MSCs may represent a promising approach for neuroprotective treatments.

scholarly journals 7,8-dihydroxyflavone Improves Neuropathological Changes in the Brain of Tg26 Mice, A Model for HIV-associated Neurocognitive Disorder

2020 ◽  
Author(s):  
Joseph Bryant ◽  
Sanketh Andhavarapu ◽  
Christopher Bever ◽  
Poornachander Guda ◽  
Akhil Katuri ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Brain Regions ◽  
Mitochondrial Damage ◽  
Data Sets ◽  
Neurocognitive Disorder ◽  
Hiv Patients ◽  
Neuroprotective Effects ◽  
Downstream Signaling ◽  
Hiv Associated Neurocognitive Disorder ◽  
The Brain

Abstract Background: The combined antiretroviral therapy (cART) era has significantly increased the lifespan of HIV patients, turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In HIV+ patients, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile.Methods: We investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. We immunohistochemically stained brain tissue sections from vehicle-treated wild type (WT), vehicle-treated Tg26, and DHF (5 mg/kg, i.p)-treated Tg26 mice to examine activation of TrkB and downstream signaling, expression of HIV-1 chemokine co-receptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. A one-way ANOVA with a Bonferroni Comparison post-hoc test was performed to analyze the data sets. Results: In the brain regions of Tg26 mice, we observed astrogliosis, increased CXCR4 and CCR5 expression, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB-Akt-NFkB signaling pathway in mediating these pathological hallmarks.Conclusions: Our study provides an overview of how targeting BDNF-TrkB signaling in the pathophysiology of HAND may be relevant for future therapies, and sheds light on 7,8 Dihydroxyflavone as a potential adjunct therapeutic agent to current antiviral therapy.

scholarly journals The use of probiotics in depression

2020 ◽  
Vol 12 ◽  
Author(s):  
Klaus W. Lange ◽  
Yukiko Nakamura ◽  
Katharina M. Lange
Keyword(s):  
Depressive Symptoms ◽  
Therapeutic Potential ◽  
Probiotic Strain ◽  
Preliminary Evidence ◽  
Single Strain ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Antidepressant Effects ◽  
Clinically Significant ◽  
Meta Analyses

Probiotics are thought to play a role in the extensive bidirectional communication between gut microbiota and the brain. A growing body of preclinical data suggests that probiotics may be effective in alleviating low mood and improving depressive symptoms. Preliminary evidence derived from studies in rodent models supports the view that single-strain or multi-strain preparations of Bifidobacterium and Lactobacillus are able to improve behaviors related to depression. The extent of antidepressant effects in humans with a clinical diagnosis of depression is less clear. While some support for the efficacy of probiotic supplementation has been found, the pooled effects in meta-analyses have generally been small. The positive effects reported for probiotics in major depression should be regarded as preliminary. Large, randomized trials assessing the efficacy of specific probiotic strain combinations over various time spans in individuals with clinically significant presentations of depression are needed to evaluate the therapeutic potential of probiotics. In light of accumulating evidence showing that probiotics may have beneficial effects in reducing depressive symptoms and may be useful as an adjunct intervention in major depressive disorder, the efficacy of probiotic foods in the prevention of depression should be investigated.

TMS in the treatment of major depressive disorder

2012 ◽  
Author(s):  
Colleen Loo
Keyword(s):  
Clinical Trials ◽  
Animal Experiments ◽  
Major Depressive ◽  
Neuroprotective Effects ◽  
Antidepressant Treatments ◽  
Stimulation Parameters ◽  
Antidepressant Effects ◽  
Growing Body ◽  
Site Stimulation

There is a growing body of literature on animal experiments using behavioural paradigms or investigations of neurobiological mechanisms to assess the antidepressant effects of repetitive (r)TMS. This article summarizes the findings from these studies. The evidence from these studies is supportive of antidepressant effects for rTMS. This evidence has provided several plausible hypotheses for the antidepressant effects of rTMS. Several studies have suggested that rTMS may have neuroprotective effects. There are many variations in the way rTMS can be given as a clinical treatment, involving choices over treatment site, stimulation parameters and treatment course. Clinical trials to date have found rTMS to be safe when given within recommended parameter guidelines. Further research is needed to understand the role of rTMS with respect to other established antidepressant treatments.

scholarly journals The heart side of brain neuromodulation

2016 ◽  
Vol 374 (2067) ◽  
pp. 20150187 ◽  
Author(s):  
Simone Rossi ◽  
Emiliano Santarnecchi ◽  
Gaetano Valenza ◽  
Monica Ulivelli
Keyword(s):  
Basal Ganglia ◽  
Brain Stimulation ◽  
Therapeutic Potential ◽  
Heart Function ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Brain Regions ◽  
Long Term Effects ◽  
Pharmacoresistant Epilepsy ◽  
Non Invasive ◽  
Vital Functions

Neuromodulation refers to invasive, minimally invasive or non-invasive techniques to stimulate discrete cortical or subcortical brain regions with therapeutic purposes in otherwise intractable patients: for example, thousands of advanced Parkinsonian patients, as well as patients with tremor or dystonia, benefited by deep brain stimulation (DBS) procedures (neural targets: basal ganglia nuclei). A new era for DBS is currently opening for patients with drug-resistant depression, obsessive-compulsive disorders, severe epilepsy, migraine and chronic pain (neural targets: basal ganglia and other subcortical nuclei or associative fibres). Vagal nerve stimulation (VNS) has shown clinical benefits in patients with pharmacoresistant epilepsy and depression. Non-invasive brain stimulation neuromodulatory techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are also being increasingly investigated for their therapeutic potential in several neurological and psychiatric disorders. In this review, we first address the most common neural targets of each of the mentioned brain stimulation techniques, and the known mechanisms of their neuromodulatory action on stimulated brain networks. Then, we discuss how DBS, VNS, rTMS and tDCS could impact on the function of brainstem centres controlling vital functions, critically reviewing their acute and long-term effects on brain sympathetic outflow controlling heart function and blood pressure. Finally, as there is clear experimental evidence in animals that brain stimulation can affect autonomic and heart functions, we will try to give a critical perspective on how it may enhance our understanding of the cortical/subcortical mechanisms of autonomic cardiovascular regulation, and also if it might find a place among therapeutic opportunities in patients with otherwise intractable autonomic dysfunctions.

scholarly journals fMRI and Transcranial Electrical Stimulation (tES): A systematic review of parameter space and outcomes

2020 ◽  
Author(s):  
Peyman Ghobadi-Azbari ◽  
Asif Jamil ◽  
Fatemeh Yavari ◽  
Zeinab Esmaeilpour ◽  
Nastaran Malmir ◽  
...  
Keyword(s):  
Systematic Review ◽  
Electrical Stimulation ◽  
Parameter Space ◽  
Brain Activity ◽  
Random Noise ◽  
Brain Regions ◽  
Transcranial Electrical Stimulation ◽  
Future Studies ◽  
Non Invasive ◽  
And Behavior

AbstractThe combination of non-invasive brain stimulation interventions with human brain mapping methods have supported research beyond correlational associations between brain activity and behavior. Functional MRI (fMRI) partnered with transcranial electrical stimulation (tES) methods, i.e., transcranial direct current (tDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation, explore the neuromodulatory effects of tES in the targeted brain regions and their interconnected networks and provide opportunities for individualized interventions. Advances in the field of tES-fMRI can be hampered by the methodological variability between studies that confounds comparability/replicability. In order to explore variability in the tES-fMRI methodological parameter space (MPS), we conducted a systematic review of 222 tES-fMRI experiments (181 tDCS, 39 tACS and 2 tRNS) published before February 1, 2019, and suggested a framework to systematically report main elements of MPS across studies. We have organized main findings in terms of fMRI modulation by tES. tES modulates activation and connectivity beyond the stimulated areas particularly with prefrontal stimulation. There were no two studies with the same MPS to replicate findings. We discuss how to harmonize the MPS to promote replication in future studies.

scholarly journals Multiple Roles in Neuroprotection for the Exercise Derived Myokine Irisin

2021 ◽  
Vol 13 ◽  
Author(s):  
Mohammad Jodeiri Farshbaf ◽  
Karina Alviña
Keyword(s):  
Skeletal Muscle ◽  
Neural Function ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Small Proteins ◽  
Antidepressant Effects ◽  
Wide Range ◽  
Fibronectin Type Iii ◽  
Membrane Bound ◽  
Fibronectin Type Iii Domain

Exercise has multiple beneficial effects on health including decreasing the risk of neurodegenerative diseases. Such effects are thought to be mediated (at least in part) by myokines, a collection of cytokines and other small proteins released from skeletal muscles. As an endocrine organ, skeletal muscle synthesizes and secretes a wide range of myokines which contribute to different functions in different organs, including the brain. One such myokine is the recently discovered protein Irisin, which is secreted into circulation from skeletal muscle during exercise from its membrane bound precursor Fibronectin type III domain-containing protein 5 (FNDC5). Irisin contributes to metabolic processes such as glucose homeostasis and browning of white adipose tissue. Irisin also crosses the blood brain barrier and initiates a neuroprotective genetic program in the hippocampus that culminates with increased expression of brain derived neurotrophic factor (BDNF). Furthermore, exercise and FNDC5/Irisin have been shown to have several neuroprotective effects against injuries in ischemia and neurodegenerative disease models, including Alzheimer’s disease. In addition, Irisin has anxiolytic and antidepressant effects. In this review we present and summarize recent findings on the multiple effects of Irisin on neural function, including signaling pathways and mechanisms involved. We also discuss how exercise can positively influence brain function and mental health via the “skeletal muscle-brain axis.” While there are still many unanswered questions, we put forward the idea that Irisin is a potentially essential mediator of the skeletal muscle-brain crosstalk.

scholarly journals 7,8-Dihydroxyflavone improves neuropathological changes in the brain of Tg26 mice, a model for HIV-associated neurocognitive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joseph Bryant ◽  
Sanketh Andhavarapu ◽  
Christopher Bever ◽  
Poornachander Guda ◽  
Akhil Katuri ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Brain Regions ◽  
Future Research ◽  
Neurocognitive Disorder ◽  
Neuroprotective Effects ◽  
Antiviral Therapies ◽  
Combined Antiretroviral Therapy ◽  
Hiv Associated Neurocognitive Disorder ◽  
The Brain

AbstractThe combined antiretroviral therapy era has significantly increased the lifespan of people with HIV (PWH), turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In PWH, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile. Therefore, we investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. In these brain regions, we observed astrogliosis, increased expression of chemokine HIV-1 coreceptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Moreover, our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB–Akt–NFkB signaling pathway in mediating these pathological hallmarks. These findings guide future research as DHF shows promise as a TrkB agonist treatment for HAND patients in adjunction to the current antiviral therapies.

Sign in / Sign up

Export Citation Format

Share Document