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 Hurdle Aerobic Exercise Increases Angiogenesis and Neuroplasticity in the Hippocampus and Improves the Spatial Memory Ability of Middle-aged Mice

2020 ◽  
Vol 8 (A) ◽  
pp. 395-402
Author(s):  
Irfannuddin Irfannuddin ◽  
Minarma Siagian ◽  
Sri Jusman ◽  
Jan Purba ◽  
Ermita Ilyas ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Spatial Memory ◽  
Aerobic Exercise ◽  
Blood Vessels ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Memory Ability ◽  
Positive Effects ◽  
Significant Difference ◽  
The Brain

BACKGROUND: Complex aerobic exercise is believed to induce positive effects on neuron structure and cognitive function. Long-term and continual cognitive stimulation increases neuroplasticity by stimulating the synthesis of neuronal growth proteins and the formation of new synapses. Exercise also increases the ability of neurons to survive and improves brain vascularization. Further investigations should be conducted to explore what types of aerobic exercise are beneficial for cognitive function. AIM: This study investigated the effects of hurdle aerobic exercise on developmentally regulated brain protein-A (Drebrin-A) as a neuroplasticity indicator, and on vascular endothelial growth factor (VEGF) as an angiogenesis marker in the hippocampus. METHODS: This study was an experimental study with post-test only control group design. Thirty-three adult mice were divided into control, hurdle aerobic runner (HAR), and plain aerobic runner (PAR) groups (n = 11 for each group). Fiberglass running wheels were originally designed and modified to assemble hurdles inside with adjustable speed. Speed adaptation was intended to achieve aerobic intensity. The experiment was performed 5 times a week for 8 weeks. The Morris water maze test (MWMT) was used to assess spatial memory ability. One day after the last running exercise and final MWMT, the mice were sacrificed and the right side of the hippocampus was obtained for Drebrin-A analysis by enzyme-linked immunosorbent assay (ELISA). The entire right side brain tissue after hippocampus was removed then used for the neuroglobin ELISA assay. To analyze VEGF expression and calculation of blood vessel, the left side of the brain was prepared for hematoxylin eosin and immunohistochemistry staining. To assess the effect of exercise on vascular widening, the analysis of the slides was performed by calculating the percentage of blood vessels with diameters more than 15 μm. One-way ANOVA and Fisher’s least significant difference test was used for statistical analysis. RESULTS: There was a significant difference in the levels of Drebrin-A between the HAR and PAR groups. Both exercise groups had higher levels of Drebrin-A than the control group. HAR and PAR groups exhibited significantly higher percentages of blood vessels expressing VEGF in hippocampus compared to control. HAR and PAR groups had the higher percentages of larger vessels compare to control. There was no significant difference of neuroglobin levels among the three groups. Both the HAR and PAR groups exhibited better spatial memory than the control group. CONCLUSION: Both aerobic exercises induced positive effects on brain angiogenesis, while the intensity of aerobic exercises did not result in high hypoxic stress in the brain.

scholarly journals Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress

2010 ◽  
Vol 104 (9) ◽  
pp. 1297-1303 ◽  
Author(s):  
Yan-Hong Huang ◽  
Qing-Hong Zhang
Keyword(s):  
Oxidative Stress ◽  
Learning And Memory ◽  
Caspase 3 ◽  
Visual Learning ◽  
Morris Water Maze Test ◽  
High Dose ◽  
Dependent Manner ◽  
Ovx Rats ◽  
Neural Apoptosis ◽  
The Brain

The present study was undertaken to investigate the antioxidant effect of chronic ingestion of genistein (Gen) against neural death in the brain of ovariectomised (Ovx) rats. The rats were randomly divided into five groups, i.e. sham-operated (sham), Ovx-only, Ovx with 17β-oestradiol, Ovx with low (15 mg/kg) and high (30 mg/kg) doses of Gen (Gen-L and Gen-H), and were orally administered daily with drugs or vehicle for 6 weeks. The learning and memory abilities were measured by Morris water maze test. Oxidative damages in the brain were evaluated by the level of superoxide dismutase (SOD), malondialdehyde (MDA) and monoamine oxidase (MAO) activities. Neural apoptosis was shown by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and caspase-3 activity. In the visual learning and memory test, there were no significant differences among the population means of the five groups. While in the probe trial test, the Gen-L group instead of the Gen-H group exhibited reduced escape latency and increased memory frequency than the Ovx group. Although both doses of Gen could reduce acetylcholinesterase activity, only a low dose of Gen could diminish MDA activity significantly in frontal cortex and enhance SOD content in the hippocampus. In contrast, MAO content was decreased in the cortex by either dose of Gen, while in the hippocampus, only a high dose of Gen appeared to be effective. Interestingly, Gen at both the doses could attenuate the increased number of TUNEL-positive neurons and caspase-3 activity in Ovx rats. These results suggest that Gen confers protection against Ovx-induced neurodegeneration by attenuating oxidative stress, lipid peroxidation and the mitochondria-mediated apoptotic pathway in a region- and dose-dependent manner.

Change of learning and memory ability and IGF-1 level in type 3 diabetes rats and effect of analog P165 of APP 5-mer peptide

2011 ◽  
Vol 26 (S2) ◽  
pp. 503-503
Author(s):  
R. Wang
Keyword(s):  
Learning And Memory ◽  
Escape Latency ◽  
Serum Glucose ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Model Group ◽  
Memory Ability ◽  
Type 3 Diabetes ◽  
Significant Difference ◽  
Type 3

ObjectiveTo investigate the effect of Analog P165 of APP5-mer peptide on change of learning and memory ability in type 3 diabetes rats.MethodHealthy adult male rats were randomly divided into 3 groups: Control group; type 3 diabetes (T3DM) group; T3DM administrated P165 group. T3DM models were induced by intracerebroventricular injection of Streptozotocin (STZ, 3 mg/kg) bilaterally. P165 groups were treated with gastric P165 (355 μg/kg) Then, learning and memory ability was detected by Morris water maze test. Body weight and serum glucose were recorded. The rat serum Insulin, Gluocagon, insulin-like growth factor-1 (IFG-1) was detected by ELISA method.ResultsIn the Morris water maze test, compared with control group, the escape latency increased significantly (p < 0.05) in model group at the 3rd day. Compared with model group, the escape latency decreased significantly (p < 0.05) in the models administrated P165 group at the 3rd day. Although there was no significant difference, the escape latency decreased in P165 group at the 4th and 5th day. From the result of rats blood serum detection, the serum IGF-1 level decreased significantly in the model group (p < 0.01) than the control group. The serum IGF-1 level increased significantly in P165 treated group(p < 0.05).The body weight and the serum glucose, insulin, gluocagon had no significant difference among the groups in the period of experiment.ConclusionThere is learning and memory impairment in the T3DM rats. P165 can raise the rats blood serum IGF-1 level, ameliorate learning and memory ability but don’t influence the serum glucose.

High Salt Elicits Brain Inflammation and Cognitive Dysfunction, Accompanied by Alternations in the Gut Microbiota and Decreased SCFA Production

2020 ◽  
Vol 77 (2) ◽  
pp. 629-640
Author(s):  
Li Hu ◽  
Shaoping Zhu ◽  
Xiaoping Peng ◽  
Kanglan Li ◽  
Wanjuan Peng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Caspase 3 ◽  
Bacterial Flora ◽  
High Salt ◽  
Brain Inflammation ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
The Brain

Background: Excessive salt intake is considered as an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. Objective: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. Methods: Adult female C57BL/6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. Results: The mice fed a HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1β, IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. Conclusion: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production.

scholarly journals Improvement of Electroacupuncture on APP/PS1 Transgenic Mice in Spatial Learning and Memory Probably due to Expression of Aβand LRP1 in Hippocampus

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xin Wang ◽  
Yanhuan Miao ◽  
Jiawula Abulizi ◽  
Fu Li ◽  
Yuping Mo ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Morris Water Maze ◽  
Normal Control ◽  
Water Maze ◽  
Normal Control Group ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
Model Group ◽  
Amyloid A

Objectives. To explore the alterations ofβ-amyloid (Aβ) and low density lipoprotein receptor-related protein-1 (LRP1) in APP/PS1 mice after electroacupuncture (EA) treatment and further to explore the mechanism.Methods. Forty 6-month-old APP/PS1 mice were randomly divided into a model group and an EA group, with twenty wild-type mice used as a normal control group. Mice in the EA group were treated with EA at GV 20 (băi huì) and bilateral KI 1 (yŏng quán) acupoints for 6 weeks. The Morris water maze was applied to assess the spatial memory in behavior. Immunohistochemistry (IHC), ELISA, Western blotting, and so forth were used to observe the expression of LRP1 and Aβ.Results. The Morris water maze test showed that, compared with the normal control group, the model group’s learning and memory capabilities were significantly decreased (P<0.05;P<0.01). The EA group was reversed (P<0.05;P<0.01). The hippocampal expression of Aβin the EA group was significantly decreased compared to the model group (P<0.01). The expression of LRP1 in the model group was significantly lower than that in the normal control group (P<0.01); the expression in the EA group was significantly higher than that in the model group (P<0.01).Conclusions. EA therapy can improve the learning and memory capabilities of APP/PS1 mice. The underlying mechanism may lie in the upregulation of an Aβtransport receptor and LRP1.

scholarly journals The Effect of Different Doses of Melatonin on Learning and Memory Deficit in Alzheimer Model of Rats

2021 ◽  
Vol 7 (1) ◽  
pp. 1-9
Author(s):  
Arman Keymoradzadeh ◽  
◽  
Alireza Komaki ◽  
Arash ‌ Bakhshi ◽  
Nafise Faraji ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Neurodegenerative Disorder ◽  
Histopathological Analysis ◽  
Age Related ◽  
Male Wistar Rats ◽  
Protection Agent ◽  
Learning And Memory Deficit ◽  
The Brain ◽  
Different Doses ◽  
Control Sham

Background: Alzheimer Disease (AD) is an age-related neurodegenerative disorder with a progressive impairment of cognitive function. The pineal gland hormone melatonin (MEL) has been known as a protection agent against AD. However, the effect of melatonin in various doses is inconsistent. Objectives: In this study, we aimed to investigate two doses of MEL on learning and memory in the amyloid-βeta (Aβ)-induced AD in the rats. Materials & Methods: Forty-eight male Wistar rats were used in the experiment and randomly divided control, sham, vehicle, AD, AD+MEL10 mg/kg, and AD+MEL 20 mg/kg groups. Intracerebroventricular injection of Aβ1–42 was used to develop the animal model of AD. Also, MEL-treated groups received an intraperitoneal injection of MEL for 4 next weeks. The Morris Water Maze (MWM) and Passive Avoidance Learning (PAL) tests were used to examine animals’ learning and memory. The brain of animals was removed for immunohistochemistry for anti- Amyloid Precursor Protein (APP). Results: Intra-peritoneal injection of MEL significantly improve learning and memory in MWM (P=0.000) and PAL test (P=0.000), but there were no significant changes in the two groups that received the melatonin (P>0.05). Histopathological analysis revealed that the clearance of APP deposition in the AD+MEL20 group was considerable compared with the AD+MEL10 group (P=0.000). Conclusion: Our findings indicate that 10 and 20 mg/kg doses of melatonin have similar results on learning and memory in the AD model. But 20 mg/kg of melatonin has significantly more effect on the clearance of APP deposition.

scholarly journals Experimental Infection by Brucella ovis: Changes in NTPDase, 5'-Nucleotidase and Acetylcholinesterase Associated Cerebral Oxidative Stres

2019 ◽  
Vol 47 (1) ◽  
Author(s):  
Géssica Perin ◽  
Anielen Dutra Silva ◽  
Nathieli Bianchi Bottari ◽  
Charles Elias Assmann ◽  
Teane Milagres Augusto Gomes ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Infected Group ◽  
Cytotoxic T Cell ◽  
Control Group ◽  
Histopathological Analysis ◽  
Lymphocyte Function ◽  
Oxygen Species ◽  
Brucella Ovis ◽  
The Brain

Background: Changes in purinergic and cholinergic signaling have been demonstrated in various pathologies associated with inflammation; however, the changes in brucellosis caused by the Gram-negative coccobacillus Brucella ovis are not known. B. ovis is generally asymptomatic in sheep. Hepatosplenomegaly has been described in B. ovis, a non-zoonotic species, characterized by an extravascular inflammatory response. Purinergic system enzymes are closely involved with the modulation of the immune system, pro- and anti-inflammatory events. The objective of this study was to investigate the role of ectonucleotidases and cholinesterase’s in the brains of mice experimentally infected with B. ovis.Materials, Methods & Results: Forty-eight animals were divided into two groups: control (n = 24) and infected (n = 24). In group infected, 100 µL containing 1.3 x 107 UFC B. ovis /mL via intraperitoneal was used in inoculation. The brains were collected from the animals on days 7, 15, 30 and 60 post-infection (PI). We measured levels of TBARS (substances reactive to thiobarbituric acid) and ROS (reactive oxygen species) in the brain. The activity of NTPDase (using ATP and ADP as substrate) and 5'-nucleotidase (using AMP as substrate) were evaluated in brain in addition to histopathological analysis. No histopathological lesions were observed in the control group nor the infected group at days 7, 15, and 30 PI. However,multifocal areas with moderate microgliosis and inflammatory infiltrates in the cerebral cortex were observed at day 60 PI in the infected animals. B. ovis DNA was detected in brain. During the course of infection, B. ovis caused greater lipid peroxidation in the brains of infected animals than in the control group at day 60PI. No significant results were observed at 7, 15 or day 30 PI. Similarly, there was significantly more reactive oxygen species at day 60 PI in brains of infected animals than in the control group. NTPDase activity (using ATP and AMP as substrate) was lower at days 7 and 15 PI in infected animals than in control. However, during the course of infection there was an increase in NTPDase activity at day 60 PI in the infected group. The infected animals showed a decrease of 5´-nucleotidase (AMP as substrate) activity at days 7 and 30 PI. On the other hand, 5´-nucleotidase activity was greater on day 60 PI in the experimental group than in the control. The results suggest that nucleotide hydrolysis was low in the acute phase (up to day 30 PI) due to the decrease of NTPDase and 5´-nucleotidase activities. After day 60 PI, there was a reversal in enzyme activities, probably with concomitant increase of extracellular nucleotides. AChE activity in brain on days 30 and 60 PI compared to control.Discussion: Among the functions of NTPDase are inhibition of platelet aggregation, vascular homeostasis, modulation of inflammation and immune response, all via its regulation of extracellular concentrations of ATP, a pro-inflammatory molecule. E-NTPDase plays an important role in controlling lymphocyte function, including antigen recognition and activation of cytotoxic T cell effector functions, as well as the generation of signals. The enzyme E-5´-nucleotidase also exerts non-enzymatic functions, including induction of intracellular signaling and mediation of cell-cell adhesion and cell-matrix and migration. Levels of acetylcholine are regulated by cholinesterase enzymes that are present in cholinergic and noncholinergic tissues, as the acetylcholinesterase (AChE) is a membrane-bound enzyme, primarily found in the brain and cholinergic neurons, where it participates in the structural regulation of postsynaptic differentiation. The results demonstrated that the chronicity of infection by B. ovis causes oxidative damage and inflammation in the brain, as well as modulation of ectonucleotidases and AChE activities.

scholarly journals Walnut Kernel administration to mothers during pregnancy and lactation improve learning of their pups. Changes in number of neurons and gene expression of NMDA receptor and BDNF in hippocampus in 80 days rat pups

2020 ◽  
Vol 33 (4) ◽  
pp. 219-224
Author(s):  
Zahra Mahmoodian ◽  
Majid Asadi Shekaari ◽  
Mansooreh Soleimani ◽  
Meysam Ahmadi-Zeidabadi ◽  
Fatemeh Moradi ◽  
...  
Keyword(s):  
Food Intake ◽  
Learning And Memory ◽  
Juglans Regia ◽  
Female Rats ◽  
Control Group ◽  
Protective Mechanism ◽  
Omega 3 ◽  
Positive Effects ◽  
Significant Difference ◽  
Pregnancy And Lactation

Abstract Walnut (Juglans regia) from the Juglandaceae family contains high levels of omega 3 fatty acid, vitamin E and melatonin, hence its consumption is beneficial to would be mothers and their offspring. The current study was designed to determine the possible mechanism of walnut consumption by mothers during pregnancy and lactation and the positive effects on learning and memory processes in their offspring. Wistar adult female rats were placed into three groups: control (fed with pellet, 20 g daily during pregnancy and lactation), CASE 1 [fed with Walnut Kernel (WK) 6% of food intake during pregnancy and lactation] and CASE 2 (fed with WK, 9% of food intake during gestation and lactation). In order to evaluate offspring learning and memory, the Morris Water Maze (MWM) test was performed for their adult offspring at 80 days of age. Histological and molecular studies were utilized in order to discover the protective mechanism and efficacy of WK consumption. The results revealed that learning was significantly improved in the females of CASE 2, in comparison to controls, while there was no difference in memory among the different groups. In addition, the number of neurons significantly increased in the CASE 2 group compared to the control group. However, the molecular study demonstrated that there was no significant difference among the study groups. The results herein show that feeding mothers with WK may improve the learning competence of their pups and increase the number of neurons in both sexes.

scholarly journals A Multimodal MR Imaging Study of the Effect of Hippocampal Damage on Affective and Cognitive Functions in a Rat Model of Chronic Exposure to a Plateau Environment

2022 ◽  
Author(s):  
Dongyong Zhu ◽  
Bo He ◽  
Mengdi Zhang ◽  
Yixuan Wan ◽  
Ruibin Liu ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Rat Model ◽  
Chronic Exposure ◽  
Imaging Techniques ◽  
Male Rats ◽  
Chemical Exchange Saturation Transfer ◽  
Tibet Plateau ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Hippocampal Damage

AbstractProlonged exposure to high altitudes above 2500 m above sea level (a.s.l.) can cause cognitive and behavioral dysfunctions. Herein, we sought to investigate the effects of chronic exposure to plateau hypoxia on the hippocampus in a rat model by using voxel-based morphometry, creatine chemical exchange saturation transfer (CrCEST) and dynamic contrast-enhanced MR imaging techniques. 58 healthy 4-week-old male rats were randomized into plateau hypoxia rats (H group) as the experimental group and plain rats (P group) as the control group. H group rats were transported from Chengdu (500 m a.s.l.), a city in a plateau located in southwestern China, to the Qinghai–Tibet Plateau (4250 m a.s.l.), Yushu, China, and then fed for 8 months there, while P group rats were fed in Chengdu (500 m a.s.l.), China. After 8 months of exposure to plateau hypoxia, open-field and elevated plus maze tests revealed that the anxiety-like behavior of the H group rats was more serious than that of the P group rats, and the Morris water maze test revealed impaired spatial memory function in the H group rats. Multimodal MR imaging analysis revealed a decreased volume of the regional gray matter, lower CrCEST contrast and higher transport coefficient Ktrans in the hippocampus compared with the P group rats. Further correlation analysis found associations of quantitative MRI parameters of the hippocampus with the behavioral performance of H group rats. In this study, we validated the viability of using noninvasive multimodal MR imaging techniques to evaluate the effects of chronic exposure to a plateau hypoxic environment on the hippocampus.

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.

Sign in / Sign up

Export Citation Format

Share Document