scholarly journals Evaluation of spatial memory and anti-fatigue function of long-term supplementation of β-alanine and confirmation through cAMP-PKA and apoptosis pathways in mice

eFood ◽  
2021 ◽  
Author(s):  
Yi-Long Ma ◽  
Yang Yang ◽  
Kiran Thakur ◽  
Carlos L. Cespedes-Acuña ◽  
Jian-Guo Zhang ◽  
...  

With an aim to explore the effects of <i>β</i>-alanine (<i>β</i>-A) on spatial memory and fatigue resistance, Kunming mice were treated with different concentrations of β-A (418, 836, and 2090 mg·kg<sup> -1</sup>·day<sup> -1</sup>). After gavage feeding with <i>β</i>-A for 10 weeks, results of the maze and MWM tests showed that <i>β</i>-A can enhance spatial learning and memory in mice. After evaluating the fatigue resistance, biochemical parameters (LG, GG, BUN, SOD, and MDA) showed significant differences in the low concentration treatment group compared to control group. Our data demonstrated that the appropriate dose of <i>β</i>-A can alleviate the oxidative stress and muscle fatigue in mice. Subsequently, expression of mRNA of key genes involved in cAMP-PKA pathway (PDE4A, MAPK1, adcy1, cAMP and CREB) was up regulated. Also, expression levels of apoptotic pathway genes were significantly affected as confirmed by qPCR and Western blotting. Our results demonstrated that <i>β</i>-A can enhance spatial learning and memory in mice via regulation of cAMP-PKA and apoptotic pathway.

2020 ◽  
Author(s):  
YuHang Zhu ◽  
JuanJuan Ren ◽  
Chao Zhang ◽  
TaoWu Gong ◽  
PengCheng Zhao ◽  
...  

Abstract Background: It has been reported that repeated exposure to sevoflurane, a widely used general anesthesia in pediatric surgeries, may lead to brain defect in infant. However, the long-term effect of repeated exposure to sevoflurane during infancy on the learning behavior and neuro-development is less investigated yet.Methods: Sixty-four SD (sprague dawley) rats were randomly divided in to two groups, the experimental group (n=32) was exposed to sevoflurane (2.6%, 2 h) and the control group (n=32) was exposed to carrier gas (1 L/min O2 + 1 L/min Air, 2 h) for three times at infancy (P (postnatal day) 7, P14, and P21). At childhood (P32 to P36), SD rats in each group (n=16) received Morris Water Maze (MWM) test, and then Magnetic Resonance Imaging (MRI) was used to scan their brain and hippocampus at P37. Subsequently, the same NWM test and MRI scanning was conducted for the remaining SD rats in their adulthood (P92 to P97) (n = 16/group).Results: After being exposed to sevoflurane in infancy, the hippocampal volume of SD rats significantly decreased in their childhood and adulthood, their whole brain volume was also shrunken in adulthood; however, MWM test showed there is no obvious change in their spatial learning and memory recall performance either in childhood or in adulthood.Conclusions: Although repeated exposure to sevoflurane in infancy did not affect the spatial learning and memory performance of rats, however, it could result in the decease of hippocampal and brain volume in their adulthood. This study suggests that repetitive sevoflurane exposure in infancy may exert long-term risk in brain development.


2021 ◽  
Vol 14 ◽  
Author(s):  
Zhan-Qiang Zhuang ◽  
Zhe-Zhe Zhang ◽  
Yue-Ming Zhang ◽  
He-Hua Ge ◽  
Shi-Yu Sun ◽  
...  

Studies have shown that gestational inflammation accelerates age-related memory impairment in mother mice. An enriched environment (EE) can improve age-related memory impairment, whereas mitochondrial dysfunction has been implicated in the pathogenesis of brain aging. However, it is unclear whether an EE can counteract the accelerated age-related memory impairment induced by gestational inflammation and whether this process is associated with the disruption of mitochondrial quality control (MQC) processes. In this study, CD-1 mice received daily intraperitoneal injections of lipopolysaccharide (LPS, 50 μg/kg) or normal saline (CON group) during gestational days 15–17 and were separated from their offspring at the end of normal lactation. The mothers that received LPS were divided into LPS group and LPS plus EE (LPS-E) treatment groups based on whether the mice were exposed to an EE until the end of the experiment. At 6 and 18 months of age, the Morris water maze test was used to evaluate spatial learning and memory abilities. Quantitative reverse transcription polymerase chain reaction and Western blot were used to measure the messenber RNA (mRNA) and protein levels of MQC-related genes in the hippocampus, respectively. The results showed that all the aged (18 months old) mice underwent a striking decline in spatial learning and memory performances and decreased mRNA/protein levels related to mitochondrial dynamics (Mfn1/Mfn2, OPA1, and Drp1), biogenesis (PGC-1α), and mitophagy (PINK1/parkin) in the hippocampi compared with the young (6 months old) mice. LPS treatment exacerbated the decline in age-related spatial learning and memory and enhanced the reduction in the mRNA and protein levels of MQC-related genes but increased the levels of PGC-1α in young mice. Exposure to an EE could alleviate the accelerated decline in age-related spatial learning and memory abilities and the accelerated changes in MQC-related mRNA or protein levels resulting from LPS treatment, especially in aged mice. In conclusion, long-term exposure to an EE can counteract the accelerated age-related spatial cognition impairment modulated by MQC in CD-1 mother mice that experience inflammation during pregnancy.


Author(s):  
Narges Marefati ◽  
Amin Mokhtari-Zaer ◽  
Farimah Beheshti ◽  
Sareh Karimi ◽  
Zahra Mahdian ◽  
...  

Abstract Background Modulatory effects of soy extract and estradiol on the central nervous system (CNS) have been reported. The effect of soy on scopolamine-induced spatial learning and memory in comparison to the effect of estradiol was investigated. Materials and methods Ovariectomized rats were divided into the following groups: (1) control, (2) scopolamine (Sco), (3) scopolamine-soy 20 (Sco-S 20), (4) scopolamine-soy 60 (Sco-S 60), (5) scopolamine-estradiol 20 (Sco-E 20) and (6) scopolamine-estradiol 60 (Sco-E 60). Soy extract, estradiol and vehicle were administered daily for 6 weeks before training in the Morris water maze (MWM) test. Scopolamine (2 mg/kg) was injected 30 min before training in the MWM test. Results In the MWM, the escape latency and traveled path to find the platform in the Sco group was prolonged compared to the control group (p < 0.001). Treatment by higher doses of soy improved performances of the rats in the MWM (p < 0.05 – p < 0.001). However, treatment with both doses of estradiol (20 and 60 μg/kg) resulted in a statistically significant improvement in the MWM (p < 0.01 – p < 0.001). Cortical, hippocampal and serum levels of malondialdehyde (MDA), as an index of lipid peroxidation, were increased which was prevented by soy extract and estradiol (p < 0.001). Cortical, hippocampal as well as serum levels of the total thiol, superoxide dismutase (SOD) and catalase (CAT) in Sco group were lower than the control group (p < 0.001) while they were enhanced when the animals were treated by soy extract and estradiol (p < 0.01 – p < 0.001). Conclusions It was observed that both soy extract and estradiol prevented learning and memory impairments induced by scopolamine in ovariectomized rats. These effects can be attributed to their protective effects on oxidative damage of the brain tissue.


2012 ◽  
Vol 73 (4) ◽  
pp. 292-301 ◽  
Author(s):  
Hideaki Nishie ◽  
Ryouhei Miyata ◽  
Ryu Fujikawa ◽  
Ken-ichi Kinoshita ◽  
Yoshikage Muroi ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ning Ding ◽  
Jing Jiang ◽  
Menghan Lu ◽  
Jiatong Hu ◽  
Yiyuan Xu ◽  
...  

Objective. To investigate the effect of manual acupuncture (MA) on NLRP3 inflammasome-related proteins. Methods. SAMP8 mice were randomly divided into Alzheimer’s disease (AD) group, the MA group, and the medicine (M) group. Mice in the M group were treated with donepezil hydrochloride at 0.65 μg/g. In the MA group, MA was applied on Baihui (GV20) and Yintang (GV29) for 20 min and then pricked at Shuigou (GV26). The Morris water maze was applied to assess spatial learning and memory. Immunohistochemical staining and western blot analysis were used to observe the expression of NLRP3 inflammasome-related proteins. Results. Compared with the normal (N) control group, spatial learning and the memory capabilities of the AD group significantly decreased (p<0.01). The number of NLRP3, ASC, Caspase-1, and IL-1β positively stained cells in the AD group was higher than the N group, and the relative expression levels of the above proteins were significantly higher than those in the N group (p<0.01). These changes were reversed by both MA and donepezil (p<0.01). Conclusion. MA can improve the learning and memory capabilities of SAMP8 mice. The negative regulation of the NLRP3/Caspase-1 pathway in the hippocampus may be a possible mechanism of MA in the treatment of AD.


2019 ◽  
Vol 8 ◽  
pp. 1182 ◽  
Author(s):  
Solmaz Khalifeh ◽  
Mehdi Khodamoradi ◽  
Vahid Hajali ◽  
Hamed Ghazvini ◽  
Lelia Eliasy ◽  
...  

Background: Methamphetamine (METH) as a synthetic psychostimulant is being increasingly recognized as a worldwide problem, which may induce memory impairment. On the other hand, it is well established that naloxone, an opiate antagonist, has some beneficial effects on learning and memory. The present research aimed at evaluating naloxone effects on spatial learning and memory impairment triggered by a neurotoxic regimen of METH in male rats. Materials and Methods: The animals received the subcutaneous (sc) regimen of METH (4×6 mg/kg at 2-h intervals), intraperitoneal (ip) naloxone (4×1 mg/kg at 2-h intervals), or normal saline at four events. The Nal-METH group of rats received four naloxone injections (1 mg/kg, ip) 30 min before each METH injection (6 mg/kg, sc) at 2-h intervals. Seven days later, they were evaluated for spatial learning and memory in the Morris Water Maze (MWM) task. Result: METH regimen induced hyperthermia, as well as a poor performance, in the acquisition and retention phases of the task, indicating spatial learning and memory impairment compared to the controls. Naloxone administration (1 mg/kg, ip) before each METH injection led to significant attenuations of both hyperthermia and METH adverse effects on the rat performance in the MWM task. Conclusion: The results revealed that pretreatment with the opiate antagonist naloxone could prevent METH adverse effects on body temperature and memory performance. It seems that the opioidergic system and hyperthermia may, at least partially, be involved in METH effects on spatial memory. [GMJ. 2019;8:e1182]


2018 ◽  
pp. 133-141 ◽  
Author(s):  
M. HOLAJOVA ◽  
M. FRANEK

Baclofen is the only clinically available metabotropic GABAB receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups. Three groups were given an injection of baclofen at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, while the fourth group was injected with saline. The injections were given after each session. Spatial learning and memory were tested using the Morris water maze, involving three types of tests: Acquisition, Probe, and Re-acquisition. This work reveals that baclofen did not affect spatial learning at any of the tested doses and regardless of the length of administration. Memory was observed to be affected, but only at the highest dose of baclofen and only temporarily. This conclusion is in line with previously published clinical cases.


2020 ◽  
Author(s):  
Junchi He ◽  
Thomas Russell ◽  
Xuecheng Qiu ◽  
Fei Hao ◽  
Michele Kyle ◽  
...  

Abstract Background Traumatic brain injury (TBI) is a major cause of death and disability in young adults worldwide. TBI-induced long-term cognitive deficits represent a growing clinical problem. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are involved in neuroprotection and neuronal plasticity. However, the knowledge concerning reparative efficacy of SCF+G-CSF treatment in post-acute TBI recovery remains incomplete. This study aims to determine the efficacy of SCF+G-CSF on post-acute TBI recovery in young adult mice. The controlled cortical impact model of TBI was used for inducing a severe damage in the motor cortex of the right hemisphere in 8-week-old male C57BL mice. SCF+G-CSF treatment was initiated 3 weeks after induction of TBI. Results Severe TBI led to persistent motor functional deficits (Rota-Rod test) and impaired spatial learning and memory (Morris water maze test). SCF+G-CSF treatment significantly improved the severe TBI-impaired spatial learning and memory 6 weeks after treatment. TBI also caused significant increases of Fluoro-Jade C positive degenerating neurons in bilateral frontal cortex, striatum and hippocampus, and significant reductions in MAP2 + apical dendrites and overgrowth of SMI312 + axons in peri-TBI cavity frontal cortex and in the ipsilateral hippocampal CA1 at 24 weeks post-TBI. SCF+G-CSF treatment significantly reduced TBI-induced neurodegeneration in the contralateral frontal cortex and hippocampal CA1, increased MAP2 + apical dendrites in the peri-TBI cavity frontal cortex, and prevented TBI-induced axonal overgrowth in both the peri-TBI cavity frontal cortex and ipsilateral hippocampal CA1. Conclusions These findings reveal a novel pathology of axonal overgrowth after TBI and demonstrate a therapeutic potential of SCF+G-CSF in ameliorating TBI-induced long-term neuronal pathology, neural network malformation, and impairments in spatial learning and memory.


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