scholarly journals Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 163
Author(s):  
Andrea Giacomini ◽  
Fiorenza Stagni ◽  
Marco Emili ◽  
Beatrice Uguagliati ◽  
Roberto Rimondini ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Critical Issue ◽  
Postnatal Period ◽  
Hippocampal Neurogenesis ◽  
Treatment Cessation ◽  
Ts65dn Mouse ◽  
Positive Effects ◽  
Tropomyosin Related Kinase B ◽  
Previous Demonstration ◽  
The Brain

No therapies currently exist for intellectual disability in Down syndrome (DS). In view of its similarities with DS, including learning and memory (L&M) defects, the Ts65Dn mouse model of DS is widely used for the design of therapy. 7,8-dihydroxyflavone (7,8-DHF), a flavonoid that targets the tropomyosin-related kinase B (TrkB) receptor of brain-derived neurotrophic factor (BDNF), exerts positive effects in various brain disease models. Based on previous demonstration that administration of 7,8-DHF in the postnatal period P3-P15 restores hippocampal neurogenesis and spinogenesis, we sought to establish whether these effects translate into behavioral benefits after treatment cessation. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) during postnatal days P3-P15 did not show any L&M improvement at one month after treatment cessation, indicating that the effects of 7,8-DHF on the brain are ephemeral. Based on evidence that chronic treatment with 7,8-DHF in juvenile Ts65Dn mice restores L&M, we sought to establish whether a similar effect is elicited in adulthood. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) for about 40 days starting from 4 months of age did not show any improvement in L&M. The results suggest that timing of therapy with 7,8-DHF is a critical issue for attainment of positive effects on the brain.

Dendrobium officinalis Flower Improves Learning and Reduces Memory Impairment by Mediating Antioxidant Effect and Balancing the Release of Neurotransmitters in Senescent Rats

2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Brain Aging ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Histopathological Analysis ◽  
Hippocampal Damage ◽  
Common Belief ◽  
Mao B ◽  
Positive Effects ◽  
The Brain

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.

scholarly journals SUN-240 Female Mice Lacking Brain Insulin Production Exhibit Learning Deficits, Anxiety, and Reduced Hippocampal Cyclin D1 Expression

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Stella Katharina Baehring ◽  
Timothy P O’Leary ◽  
Danae M Holenka ◽  
Hong Li ◽  
Kyungchan Kim ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Learning And Memory ◽  
Brain Region ◽  
Stress Reactivity ◽  
Memory Performance ◽  
Acquisition Training ◽  
Hippocampal Neurogenesis ◽  
Wild Type ◽  
Female Mice ◽  
The Brain

Abstract Insulin dysregulation independently underlies diabetes and Alzheimer’s Disease (AD) pathology. However, the former has also been shown to be a risk factor for the latter. The ancestral insulin gene (Ins2), but not the pancreas-specific Ins1gene, is transcribed locally within the brain in mice. We confirmed that neuronal expression of Ins2 is most prominent within the hippocampus, a brain region with established roles in learning and memory, and that it was reduced by a diet known to promote neuronal dysfunction. It is not yet clear, however, how insulin produced locally within the brain influences hippocampal function, learning and memory. To eliminate brain-derived insulin, we used young and old mice with germline Ins2knockout (Ins2-/-) and their normal complement of wildtype Ins1 alleles, which had equivalent pancreatic insulin and normal glucose homeostasis. Using the Morris water maze, we found that learning and memory performance of female Ins2-/-mice was significantly impaired relative to wild-type mice, whereas the performance of male Ins2-/-and wild-type mice did not differ. During acquisition training, the swim-speed in female Ins2-/-was faster than wild-type mice, suggesting increased stress reactivity and motivation to escape from water. Indeed, anxiety-like behavior was increased in female mice as assessed by the open-field test. Using RNA sequencing to profile isolated hippocampi, we found that femaleIns2-/-mice had a significant reduction in Cyclin D1 (Ccnd1) compared with littermate controls. This observation points to a possible defect in hippocampal neurogenesis, a physiological hallmark of impaired memory and emotionality implicated in both, diabetes and AD. Together these data suggest that Ins2plays sex- and brain region-specific roles in neuronal function and perhaps adult neurogenesis.

scholarly journals Plasma dilution improves cognition and attenuates neuroinflammation in old mice

GeroScience ◽  
2020 ◽  
Author(s):  
Melod Mehdipour ◽  
Taha Mehdipour ◽  
Colin M. Skinner ◽  
Nathan Wong ◽  
Chao Liu ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Brain Health ◽  
Positive Effects ◽  
Blood Exchange ◽  
Mammalian Tissues ◽  
Systemic Factors ◽  
Secretory Phenotype ◽  
And Function ◽  
Old Mice ◽  
The Brain

AbstractOur recent study has established that young blood factors are not causal, nor necessary, for the systemic rejuvenation of mammalian tissues. Instead, a procedure referred to as neutral blood exchange (NBE) that resets signaling milieu to a pro-regenerative state through dilution of old plasma, enhanced the health and repair of the muscle and liver, and promoted better hippocampal neurogenesis in 2-year-old mice (Mehdipour et al., Aging 12:8790–8819, 2020). Here we expand the rejuvenative phenotypes of NBE, focusing on the brain. Namely, our results demonstrate that old mice perform much better in novel object and novel texture (whisker discrimination) tests after a single NBE, which is accompanied by reduced neuroinflammation (less-activated CD68+ microglia). Evidence against attenuation/dilution of peripheral senescence-associated secretory phenotype (SASP) as the main mechanism behind NBE was that the senolytic ABT 263 had limited effects on neuroinflammation and did not enhance hippocampal neurogenesis in the old mice. Interestingly, peripherally acting ABT 263 and NBE both diminished SA-βGal signal in the old brain, demonstrating that peripheral senescence propagates to the brain, but NBE was more robustly rejuvenative than ABT 263, suggesting that rejuvenation was not simply by reducing senescence. Explaining the mechanism of the positive effects of NBE on the brain, our comparative proteomics analysis demonstrated that dilution of old blood plasma yields an increase in the determinants of brain maintenance and repair in mice and in people. These findings confirm the paradigm of rejuvenation through dilution of age-elevated systemic factors and extrapolate it to brain health and function.

Learning, Neurogenesis, and Effects of Flavonoids on Learning

2021 ◽  
Vol 21 ◽  
Author(s):  
Asan Yalmaz Hasan Almulla ◽  
Rasim Mogulkoc ◽  
Abdulkerim Kasim Baltaci ◽  
Dervis Dasdelen
Keyword(s):  
Learning And Memory ◽  
Neural Circuits ◽  
Brain Regions ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Factors Affecting ◽  
Different Types ◽  
Mature Neurons ◽  
Dependent Learning ◽  
The Brain

: Learning and memory are two of our mind's most magical abilities. Different brain regions have roles in processing and storing different types of memories. The hippocampus is the part of the brain responsible for receiving information and storing it in the neocortex. One of the most impressive characteristics of the hippocampus is its capacity for neurogenesis, which is a process in which new neurons are produced and then transformed into mature neurons and finally integrated into neural circuits. The neurogenesis process in the hippocampus, an example of neuroplasticity in the adult brain, is believed to aid hippocampal-dependent learning and memory. New neurons are constantly produced in the hippocampus and integrated into the pre-existing neuronal network; this allows old memories already stored in the neocortex to be removed from the hippocampus and replaced with new ones. Factors affecting neurogenesis in the hippocampus may also affect hippocampal-dependent learning and memory. The flavonoids can particularly exert powerful actions in mammalian cognition and improve hippocampal-dependent learning and memory by positively affecting hippocampal neurogenesis.

scholarly journals Polyphenol-rich extract from grape and blueberry attenuates cognitive decline and improves neuronal function in aged mice

2018 ◽  
Vol 7 ◽  
Author(s):  
Julien Bensalem ◽  
Stéphanie Dudonné ◽  
David Gaudout ◽  
Laure Servant ◽  
Frédéric Calon ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Learning And Memory ◽  
High Performance ◽  
Brain Plasticity ◽  
Memory Deficits ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Native Form ◽  
Age Related ◽  
The Brain

AbstractAgeing is characterised by memory deficits, associated with brain plasticity impairment. Polyphenols from berries, such as flavan-3-ols, anthocyanins, and resveratrol, have been suggested to modulate synaptic plasticity and cognitive processes. In the present study we assessed the preventive effect of a polyphenol-rich extract from grape and blueberry (PEGB), with high concentrations of flavonoids, on age-related cognitive decline in mice. Adult and aged (6 weeks and 16 months) mice were fed a PEGB-enriched diet for 14 weeks. Learning and memory were assessed using the novel object recognition and Morris water maze tasks. Brain polyphenol content was evaluated with ultra-high-performance LC-MS/MS. Hippocampal neurotrophin expression was measured using quantitative real-time PCR. Finally, the effect of PEGB on adult hippocampal neurogenesis was assessed by immunochemistry, counting the number of cells expressing doublecortin and the proportion of cells with dendritic prolongations. The combination of grape and blueberry polyphenols prevented age-induced learning and memory deficits. Moreover, it increased hippocampal nerve growth factor (Ngf) mRNA expression. Aged supplemented mice displayed a greater proportion of newly generated neurons with prolongations than control age-matched mice. Some of the polyphenols included in the extract were detected in the brain in the native form or as metabolites. Aged supplemented mice also displayed a better survival rate. These data suggest that PEGB may prevent age-induced cognitive decline. Possible mechanisms of action include a modulation of brain plasticity. Post-treatment detection of phenolic compounds in the brain suggests that polyphenols may act directly at the central level, while they can make an impact on mouse survival through a potential systemic effect.

scholarly journals Sublethal Exposure Effects of the Neonicotinoid Clothianidin Strongly Modify the Brain Transcriptome and Proteome in the Male Moth Agrotis ipsilon

Insects ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 152
Author(s):  
Camille Meslin ◽  
Françoise Bozzolan ◽  
Virginie Braman ◽  
Solenne Chardonnet ◽  
Cédric Pionneau ◽  
...  
Keyword(s):  
Sex Pheromone ◽  
Molecular Mechanisms ◽  
Insect Pest ◽  
Agrotis Ipsilon ◽  
Positive Effects ◽  
Male Moth ◽  
Hormetic Effect ◽  
Pest Insects ◽  
Neuronal Processes ◽  
The Brain

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids such as clothianidin. The residual accumulation of low concentrations of these insecticides can have positive effects on target pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction and olfactory synaptic transmission is cholinergic, neonicotinoid residues could indeed modify chemical communication. We recently showed that treatments with low doses of clothianidin could induce hormetic effects on behavioral and neuronal sex pheromone responses in the male moth, Agrotis ipsilon. In this study, we used high-throughput RNAseq and proteomic analyses from brains of A. ipsilon males that were intoxicated with a low dose of clothianidin to investigate the molecular mechanisms leading to the observed hormetic effect. Our results showed that clothianidin induced significant changes in transcript levels and protein quantity in the brain of treated moths: 1229 genes and 49 proteins were differentially expressed upon clothianidin exposure. In particular, our analyses highlighted a regulation in numerous enzymes as a possible detoxification response to the insecticide and also numerous changes in neuronal processes, which could act as a form of acclimatization to the insecticide-contaminated environment, both leading to enhanced neuronal and behavioral responses to sex pheromone.

scholarly journals Neuroprotective Benefits of Exercise and MitoQ on Memory Function, Mitochondrial Dynamics, Oxidative Stress, and Neuroinflammation in D-Galactose-Induced Aging Rats

2021 ◽  
Vol 11 (2) ◽  
pp. 164
Author(s):  
Jae-Hoon Jeong ◽  
Jung-Hoon Koo ◽  
Jang Soo Yook ◽  
Joon-Yong Cho ◽  
Eun-Bum Kang
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Cognitive Impairment ◽  
Nadph Oxidase ◽  
Learning And Memory ◽  
Oxidase Activity ◽  
Mitochondrial Dynamics ◽  
Nadph Oxidase Activity ◽  
Aging Rats ◽  
Positive Effects

Exercise and antioxidants have health benefits that improve cognitive impairment and may act synergistically. In this study, we examined the effects of treadmill exercise (TE) and mitochondria-targeted antioxidant mitoquinone (MitoQ), individually or combined, on learning and memory, mitochondrial dynamics, NADPH oxidase activity, and neuroinflammation and antioxidant activity in the hippocampus of D-galactose-induced aging rats. TE alone and TE combined with MitoQ in aging rats reduced mitochondrial fission factors (Drp1, Fis1) and increased mitochondrial fusion factors (Mfn1, Mfn2, Opa1). These groups also exhibited improved NADPH oxidase activity and antioxidant activity (SOD-2, catalase). TE or MitoQ alone decreased neuroinflammatory response (COX-2, TNF-α), but the suppression was greater with their combination. In addition, aging-increased neuroinflammation in the dentate gyrus was decreased in TE but not MitoQ treatment. Learning and memory tests showed that, contrarily, MitoQ alone demonstrated some similar effects to TE but not a definitive improvement. In conclusion, this study demonstrated that MitoQ exerted some positive effects on aging when used as an isolated treatment, but TE had a more effective role on cognitive impairment, oxidative stress, inflammation, and mitochondria dysfunction. Our findings suggest that the combination of TE and MitoQ exerted no synergistic effects and indicated regular exercise should be the first priority in neuroprotection of age-related cognitive decline.

scholarly journals GABAB receptor antagonist promotes hippocampal neurogenesis and facilitates cognitive function recovery following acute cerebral ischemia in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Song ◽  
Yaohua Chen ◽  
Cheng Chen ◽  
Lili Chen ◽  
Oumei Cheng
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurogenesis ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
In Vitro Experiments ◽  
Adult Mice

Abstract Purpose and background Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Methods Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. Results CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Conclusion Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI.

scholarly journals Lack of Skeletal Muscle Serotonin Impairs Physical Performance

2021 ◽  
Vol 14 ◽  
pp. 117864692110031
Author(s):  
Marion Falabrègue ◽  
Anne-Claire Boschat ◽  
Romain Jouffroy ◽  
Marieke Derquennes ◽  
Haidar Djemai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Physical Performance ◽  
Depressive Disorders ◽  
Tryptophan Metabolism ◽  
Long Distance ◽  
Positive Effects ◽  
Tryptophan Metabolites ◽  
The Brain ◽  
Deficient Mice

Low levels of the neurotransmitter serotonin have been associated with the onset of depression. While traditional treatments include antidepressants, physical exercise has emerged as an alternative for patients with depressive disorders. Yet there remains the fundamental question of how exercise is sensed by the brain. The existence of a muscle–brain endocrine loop has been proposed: according to this scenario, exercise modulates metabolization of tryptophan into kynurenine within skeletal muscle, which in turn affects the brain, enhancing resistance to depression. But the breakdown of tryptophan into kynurenine during exercise may also alter serotonin synthesis and help limit depression. In this study, we investigated whether peripheral serotonin might play a role in muscle–brain communication permitting adaptation for endurance training. We first quantified tryptophan metabolites in the blood of 4 trained athletes before and after a long-distance trail race and correlated changes in tryptophan metabolism with physical performance. In parallel, to assess exercise capacity and endurance in trained control and peripheral serotonin–deficient mice, we used a treadmill incremental test. Peripheral serotonin–deficient mice exhibited a significant drop in physical performance despite endurance training. Brain levels of tryptophan metabolites were similar in wild-type and peripheral serotonin–deficient animals, and no products of muscle-induced tryptophan metabolism were found in the plasma or brains of peripheral serotonin–deficient mice. But mass spectrometric analyses revealed a significant decrease in levels of 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in both the soleus and plantaris muscles, demonstrating that metabolization of tryptophan into serotonin in muscles is essential for adaptation to endurance training. In light of these findings, the breakdown of tryptophan into peripheral but not brain serotonin appears to be the rate-limiting step for muscle adaptation to endurance training. The data suggest that there is a peripheral mechanism responsible for the positive effects of exercise, and that muscles are secretory organs with autocrine-paracrine roles in which serotonin has a local effect.

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