scholarly journals Testosterone and Adult Neurogenesis

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 225 ◽  
Author(s):  
Mark D. Spritzer ◽  
Ethan A. Roy
Keyword(s):  
Adult Neurogenesis ◽  
Neurological Diseases ◽  
Field Studies ◽  
Brain Regions ◽  
Neuroprotective Effects ◽  
Laboratory Rodents ◽  
Functional Consequences ◽  
Induced Changes ◽  
Dentate Gyrus Region

It is now well established that neurogenesis occurs throughout adulthood in select brain regions, but the functional significance of adult neurogenesis remains unclear. There is considerable evidence that steroid hormones modulate various stages of adult neurogenesis, and this review provides a focused summary of the effects of testosterone on adult neurogenesis. Initial evidence came from field studies with birds and wild rodent populations. Subsequent experiments with laboratory rodents have tested the effects of testosterone and its steroid metabolites upon adult neurogenesis, as well as the functional consequences of induced changes in neurogenesis. These experiments have provided clear evidence that testosterone increases adult neurogenesis within the dentate gyrus region of the hippocampus through an androgen-dependent pathway. Most evidence indicates that androgens selectively enhance the survival of newly generated neurons, while having little effect on cell proliferation. Whether this is a result of androgens acting directly on receptors of new neurons remains unclear, and indirect routes involving brain-derived neurotrophic factor (BDNF) and glucocorticoids may be involved. In vitro experiments suggest that testosterone has broad-ranging neuroprotective effects, which will be briefly reviewed. A better understanding of the effects of testosterone upon adult neurogenesis could shed light on neurological diseases that show sex differences.

scholarly journals Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

2020 ◽  
Vol 21 (10) ◽  
pp. 3575 ◽  
Author(s):  
Viviana di Giacomo ◽  
Annalisa Chiavaroli ◽  
Lucia Recinella ◽  
Giustino Orlando ◽  
Amelia Cataldi ◽  
...  
Keyword(s):  
Kynurenic Acid ◽  
Cannabis Sativa ◽  
Ex Vivo ◽  
Neurological Diseases ◽  
Docking Studies ◽  
Experimental Models ◽  
Neuroprotective Effects ◽  
Rat Astrocytes ◽  
Species Production

Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols. Although CBD’s effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.

scholarly journals Xylazine regulates the release of glycine and aspartic acid in rat brain

2018 ◽  
Vol 62 (1) ◽  
pp. 121-128
Author(s):  
Yi-Ming Zhang ◽  
Dong-Xu Yu ◽  
Bai-Shuang Yin ◽  
Xin-Ran Li ◽  
Li-Na Li ◽  
...  
Keyword(s):  
Aspartic Acid ◽  
Brain Area ◽  
Brain Regions ◽  
Inhibitory Effect ◽  
Test Methods ◽  
Control Group ◽  
Clinical Anaesthesia ◽  
Induced Changes ◽  
Dose Dependent

AbstractIntroductionXylazine, a type of α2-adrenoceptors, is a commonly used drug in veterinary medicine. Xylazine-induced changes in the content of amino acid neurotransmitters – glycine (Gly) and aspartic acid (Asp), in different brain regions and neurons were studied.Material and MethodsWistar rats were administered 50 mg/kg or 70 mg/kg of xylazine by intraperitoneal injection. In addition, in vitro experiments were conducted, in which neurons were treated with 15 μg/mL, 25 μg/mL, 35μg/mL, and 45 μg/mL of xylazine. Test methods were based on the enzyme-linked immunosorbent assays (ELISA).ResultsDuring anaesthesia, Asp levels in each brain area were significantly lower compared to the control group. Except for the cerebrum, levels of Gly in other brain areas were significantly increased during the anaesthesia period. In vitro, xylazine-related neuron secretion of Gly increased significantly compared to the control group at 60 min and 90 min. Moreover, xylazine caused a significant decrease in the levels of Asp secreted by neurons at 20 min, but gradually returned to the level of the control group.ConclusionThe data showed that during anaesthesia the overall levels of Asp decreased and overall levels of Gly increased. In addition, the inhibitory effect of xylazine on Asp and the promotion of Gly were dose-dependent. Our data showed that different effects of xylazine on excitatory and inhibitory neurotransmitters provided a theoretical basis for the mechanism of xylazine activity in clinical anaesthesia.

scholarly journals Pitavastatin Ameliorates Lipopolysaccharide-Induced Blood-Brain Barrier Dysfunction

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 837
Author(s):  
Takashi Fujimoto ◽  
Yoichi Morofuji ◽  
Andrej Kovac ◽  
Michelle A. Erickson ◽  
Mária A. Deli ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Neuroprotective Effects ◽  
Blood Brain ◽  
Mouse Brain Endothelial Cells ◽  
Pharmacological Significance ◽  
Primary Mouse

Statins have neuroprotective effects on neurological diseases, including a pleiotropic effect possibly related to blood–brain barrier (BBB) function. In this study, we investigated the effects of pitavastatin (PTV) on lipopolysaccharide (LPS)-induced BBB dysfunction in an in vitro BBB model comprising cocultured primary mouse brain endothelial cells, pericytes, and astrocytes. LPS (1 ng/mL, 24 h) increased the permeability and lowered the transendothelial electrical resistance of the BBB, and the co-administration of PTV prevented these effects. LPS increased the release of interleukin-6, granulocyte colony-stimulating factor, keratinocyte-derived chemokine, monocyte chemotactic protein-1, and regulated on activation, normal T-cell expressed and secreted from the BBB model. PTV inhibited the LPS-induced release of these cytokines. These results suggest that PTV can ameliorate LPS-induced BBB dysfunction, and these effects might be mediated through the inhibition of LPS-induced cytokine production. Clinically, therapeutic approaches using statins combined with novel strategies need to be designed. Our present finding sheds light on the pharmacological significance of statins in the treatment of central nervous system diseases.

scholarly journals Protective Effects and Mechanism of Radix Polygalae Against Neurological Diseases as Well as Effective Substance

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Jiang ◽  
Shanshan Wei ◽  
Yiwen Zhang ◽  
Wenlu He ◽  
Haiyue Pei ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Chinese Herb ◽  
Receptor Activation ◽  
Mechanisms Of Action ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Apoptotic Effects

Radix Polygalae (also known as Yuanzhi in China) is the dried rhizome of Polygala tenuifolia Willd. or Polygala sibirica L., which is a famous Chinese herb and has been widely used for centuries in traditional medicines including expectorants, tonics, tranquilizers, antipsychotic, and so on. This article reviews the neuroprotective effects of Radix Polygalae in preclinical models of central nervous system (CNS) disorders, especially anxiety, depression, declining cognition, Alzheimer's disease (AD), and Parkinson's disease (PD). The chemical composition of Radix Polygalae as well as the underlying mechanisms of action were also reviewed. We found that Radix Polygalae possesses a broad range of beneficial effects on the abovementioned conditions. The multifold mechanisms of action include several properties such as antioxidant and associated apoptotic effects; anti-inflammatory and associated apoptotic effects; neurogenesis, regeneration, differentiation, and neuronal plasticity improvement; hypothalamic–pituitary–adrenal axis (HPA) regulation; neurotransmitter release; and receptor activation (A2AR, NMDA-R, and GluR). Nevertheless, the detailed mechanisms underlying this array of pharmacological effects observed in vitro and in vivo still need further investigation to attain a coherent neuroprotective profile.

scholarly journals Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain

2007 ◽  
Vol 363 (1489) ◽  
pp. 101-122 ◽  
Author(s):  
Jan Kaslin ◽  
Julia Ganz ◽  
Michael Brand
Keyword(s):  
Olfactory Bulb ◽  
Adult Neurogenesis ◽  
Brain Plasticity ◽  
Brain Regions ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Embryonic Neurogenesis ◽  
Vertebrate Brain ◽  
Multipotent Progenitor Cells

Post-embryonic neurogenesis is a fundamental feature of the vertebrate brain. However, the level of adult neurogenesis decreases significantly with phylogeny. In the first part of this review, a comparative analysis of adult neurogenesis and its putative roles in vertebrates are discussed. Adult neurogenesis in mammals is restricted to two telencephalic constitutively active zones. On the contrary, non-mammalian vertebrates display a considerable amount of adult neurogenesis in many brain regions. The phylogenetic differences in adult neurogenesis are poorly understood. However, a common feature of vertebrates (fish, amphibians and reptiles) that display a widespread adult neurogenesis is the substantial post-embryonic brain growth in contrast to birds and mammals. It is probable that the adult neurogenesis in fish, frogs and reptiles is related to the coordinated growth of sensory systems and corresponding sensory brain regions. Likewise, neurons are substantially added to the olfactory bulb in smell-oriented mammals in contrast to more visually oriented primates and songbirds, where much fewer neurons are added to the olfactory bulb. The second part of this review focuses on the differences in brain plasticity and regeneration in vertebrates. Interestingly, several recent studies show that neurogenesis is suppressed in the adult mammalian brain. In mammals, neurogenesis can be induced in the constitutively neurogenic brain regions as well as ectopically in response to injury, disease or experimental manipulations. Furthermore, multipotent progenitor cells can be isolated and differentiated in vitro from several otherwise silent regions of the mammalian brain. This indicates that the potential to recruit or generate neurons in non-neurogenic brain areas is not completely lost in mammals. The level of adult neurogenesis in vertebrates correlates with the capacity to regenerate injury, for example fish and amphibians exhibit the most widespread adult neurogenesis and also the greatest capacity to regenerate central nervous system injuries. Studying these phenomena in non-mammalian vertebrates may greatly increase our understanding of the mechanisms underlying regeneration and adult neurogenesis. Understanding mechanisms that regulate endogenous proliferation and neurogenic permissiveness in the adult brain is of great significance in therapeutical approaches for brain injury and disease.

scholarly journals Resveratrol Delivery from Implanted Cyclodextrin Polymers Provides Sustained Antioxidant Effect on Implanted Neural Probes

2020 ◽  
Vol 21 (10) ◽  
pp. 3579 ◽  
Author(s):  
Rebecca M. Haley ◽  
Sean T. Zuckerman ◽  
Hassan Dakhlallah ◽  
Jeffery R. Capadona ◽  
Horst A. von Recum ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurological Diseases ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
The Novel ◽  
Systemic Delivery ◽  
Neuroprotective Effects

Intracortical microelectrodes are valuable tools used to study and treat neurological diseases. Due in large part to the oxidative stress and inflammatory response occurring after electrode implantation, the signal quality of these electrodes decreases over time. To alleviate this response, resveratrol, a natural antioxidant which elicits neuroprotective effects through reduction of oxidative stress, was utilized. This work compares traditional systemic delivery of resveratrol to the novel cyclodextrin polymer (pCD) local delivery approach presented herein, both in vitro and in vivo. The pCD displayed an extended resveratrol release for 100 days, as well as 60 days of free radical scavenging activity in vitro. In vivo results indicated that our pCD delivery system successfully delivered resveratrol to the brain with a sustained release for the entire short-duration study (up to 7 days). Interestingly, significantly greater concentrations of resveratrol metabolites were found at the intracortical probe implantation site compared to the systemic administration of resveratrol. Together, our pilot results provide support for the possibility of improving the delivery of resveratrol in an attempt to stabilize long-term neural interfacing applications.

Melatonin attenuates microglial activation and improves neurological functions in rat model of collagenase-induced intracerebral hemorrhage

2021 ◽  
Vol 4 (2) ◽  
pp. 360-376
Author(s):  
Joseph Wai-Hin Leung ◽  
Raymond Tak Fai Cheung
Keyword(s):  
Intracerebral Hemorrhage ◽  
Cell Viability ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Neurological Diseases ◽  
Brain Parenchyma ◽  
Neurological Deficits ◽  
Neuroprotective Effects ◽  
Permanent Disability

Intracerebral hemorrhage (ICH) is a severe form of stroke with a high mortality rate. It is also an important cause of permanent disability. Apart from hematoma growth and edema development, inflammatory responses and oxidative stress are responsible for poor outcomes after ICH. Due to its antioxidant, anti-inflammatory and anti-apoptotic properties, melatonin is a neuroprotective molecule against different neurological diseases. The protective roles of melatonin on ICH, particularly in the collagenase-induced ICH model, have not been well studied. The present study aims to explore neuroprotective effects of melatonin against ICH. At 24 hours after ICH induction, rats exhibited neurological deficits with mild loss in body weight (BW). Hematoma was found in the brain parenchyma with ED-1+ activated microglia and TUNEL+ apoptotic cells in the perihematomal region. As an in vitro model of ICH, SH-SY5Y cells were treated with red blood cell lysate. This treatment significantly reduced cell viability; however, melatonin (10-5 M) restored the cell viability. At 72 hours after ICH, rats treated with melatonin (50 mg/kg) at 2, 24 and 48 hours had reduced perihematomal microglial activation. However, there was no effect on hematoma size or perihematomal apoptosis. We further treated rats with 50 mg/kg melatonin starting at 2 hours and repeating at 24-hour intervals for two or seven more days. Both melatonin treatments improved post-ICH neurological functions, and the effect was most pronounced at 4 days after ICH. Since studies regarding the protective roles of melatonin on ICH remain very limited, our study advances our understanding of the potential use of melatonin as a treatment for ICH.

scholarly journals SimpylCellCounter: An Automated Solution for Quantifying Cells in Brain Tissue

2020 ◽  
Author(s):  
Aneesh Bal ◽  
Fidel Maureira ◽  
Amy A. Arguello
Keyword(s):  
Brain Tissue ◽  
Absolute Error ◽  
Brain Regions ◽  
Neural Network Classifier ◽  
New Approach ◽  
General Utility ◽  
Automated Method ◽  
Induced Changes ◽  
Automated Tool

ABSTRACTRationale & ObjectiveManual quantification of activated cells can provide valuable information about stimuli-induced changes within brain regions; however, this analysis remains time intensive. Therefore, we created SimpylCellCounter (SCC), an automated method to quantify cells that express Cfos protein, an index of neuronal activity, in brain tissue and benchmarked it against two widely-used methods: OpenColonyFormingUnit (OCFU) and ImageJ Edge Detection Macro (IMJM).MethodsIn Experiment 1, manually-obtained counts were compared to those detected via OCFU, IMJM and SCC. The absolute error in counts (manual versus automated method) was calculated, and error types were categorized as false positives or negatives. In Experiment 2, performance analytics of OCFU, IMJM and SCC were compared. In Experiment 3, SCC performed analysis on images it was not trained on, to assess its general utility.Results & ConclusionsWe found SCC to be highly accurate and efficient in quantifying both cells with circular morphologies and those expressing Cfos. Additionally, SCC utilizes a new approach for counting overlapping cells with a pretrained convolutional neural network classifier. The current study demonstrates that SCC is a novel, automated tool to quantify cells in brain tissue, complementing current, open-sourced quantification methods designed to detect cells in vitro.

Dexmedetomidine protects against lidocaine-induced neurotoxicity through SIRT1 downregulation-mediated activation of FOXO3a

2020 ◽  
Vol 39 (9) ◽  
pp. 1213-1223 ◽  
Author(s):  
L-N Zheng ◽  
F-Q Guo ◽  
Z-S Li ◽  
Z Wang ◽  
J-H Ma ◽  
...  
Keyword(s):  
Protein Level ◽  
Sirtuin 1 ◽  
Apoptotic Pathway ◽  
Neuroprotective Effects ◽  
In Vivo Models ◽  
Theoretical Support ◽  
Novel Target ◽  
Induced Changes

Lidocaine, a typical local anesthetic, has been shown to directly induce neurotoxicity in clinical settings. Dexmedetomidine (DEX) is an alpha-2-adrenoreceptor agonist that has been used as anxiolytic, sedative, and analgesic agent which has recently found to protect against lidocaine-induced neurotoxicity. Nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-1 (SIRT1)/forkhead box O3 (FOXO3a) signaling is critical for maintaining neuronal function and regulation of the apoptotic pathway. In the present study, we designed in vitro and in vivo models to investigate the potential effects of lidocaine and DEX on SIRT1 and FOXO3a and to verify whether SIRT1/FOXO3a-mediated regulation of apoptosis is involved in DEX-induced neuroprotective effects against lidocaine. We found that in both PC12 cells and brains of mice, lidocaine decreased SIRT1 level through promoting the degradation of SIRT1 protein. Lidocaine also increased FOXO3a protein level and increased the acetylation of SIRT1 through inhibiting SIRT1. Upregulation of SIRT1 or downregulation of FOXO3a significantly inhibited lidocaine-induced changes in both cell viability and apoptosis. DEX significantly inhibited the lidocaine-induced decrease of SIRT1 protein level and increase of FOXO3a protein level and acetylation of FOXO3a. Downregulation of SIRT1 or upregulation of FOXO3a suppressed DEX-induced neuroprotective effects against lidocaine. The data suggest that SIRT1/FOXO3a is a potential novel target for alleviating lidocaine-induced neurotoxicity and provide more theoretical support for the use of DEX as an effective adjunct to alleviate chronic neurotoxicity induced by lidocaine.

scholarly journals Human cerebral organoids establish subcortical projections in the mouse brain after transplantation

2020 ◽  
Author(s):  
Xin Dong ◽  
Shi-Bo Xu ◽  
Xin Chen ◽  
Mengdan Tao ◽  
Xiao-Yan Tang ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Brain Regions ◽  
Synaptic Connections ◽  
Glutamatergic Neurons ◽  
Human Brain Development ◽  
Basal Brain

Abstract Numerous studies have used human pluripotent stem cell-derived cerebral organoids to elucidate the mystery of human brain development and model neurological diseases in vitro, but the potential for grafted organoid-based therapy in vivo remains unknown. Here, we optimized a culturing protocol capable of efficiently generating small human cerebral organoids. After transplantation into the mouse medial prefrontal cortex, the grafted human cerebral organoids survived and extended projections over 4.5 mm in length to basal brain regions within 1 month. The transplanted cerebral organoids generated human glutamatergic neurons that acquired electrophysiological maturity in the mouse brain. Importantly, the grafted human cerebral organoids functionally integrated into pre-existing neural circuits by forming bidirectional synaptic connections with the mouse host neurons. Furthermore, compared to control mice, the mice transplanted with cerebral organoids showed an increase in freezing time in response to auditory conditioned stimuli, suggesting the potentiation of the startle fear response. Our study showed that subcortical projections can be established by microtransplantation and may provide crucial insights into the therapeutic potential of human cerebral organoids for neurological diseases.

Sign in / Sign up

Export Citation Format

Share Document