scholarly journals Chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile X mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Patricia Cogram ◽  
Daniel L. Alkon ◽  
David Crockford ◽  
Robert M. J. Deacon ◽  
Michael J. Hurley ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Fragile X ◽  
Autism Spectrum ◽  
Spatial Learning And Memory ◽  
Therapeutic Effects ◽  
Long Term Effects ◽  
Bryostatin 1 ◽  
Short Period

Abstract Fragile X syndrome (FXS), an X-chromosome linked intellectual disability, is the leading monogenetic cause of autism spectrum disorder (ASD), a neurodevelopmental condition that currently has no specific drug treatment. Building upon the demonstrated therapeutic effects on spatial memory of bryostatin-1, a relatively specific activator of protein kinase C (PKC)ε, (also of PKCα) on impaired synaptic plasticity/maturation and spatial learning and memory in FXS mice, we investigated whether bryostatin-1 might affect the autistic phenotypes and other behaviors, including open field activity, activities of daily living (nesting and marble burying), at the effective therapeutic dose for spatial memory deficits. Further evaluation included other non-spatial learning and memory tasks. Interestingly, a short period of treatment (5 weeks) only produced very limited or no therapeutic effects on the autistic and cognitive phenotypes in the Fmr1 KO2 mice, while a longer treatment (13 weeks) with the same dose of bryostatin-1 effectively rescued the autistic and non-spatial learning deficit cognitive phenotypes. It is possible that longer-term treatment would result in further improvement in these fragile X phenotypes. This effect is clearly different from other treatment strategies tested to date, in that the drug shows little acute effect, but strong long-term effects. It also shows no evidence of tolerance, which has been a problem with other drug classes (mGluR5 antagonists, GABA-A and -B agonists). The results strongly suggest that, at appropriate dosing and therapeutic period, chronic bryostatin-1 may have great therapeutic value for both ASD and FXS.

scholarly journals Modulation of Cognition: The Role of Gnidia glauca on Spatial Learning and Memory Retention in High-Fat Diet-Induced Obese Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
Wycliffe Makori Arika ◽  
Cromwell Mwiti Kibiti ◽  
Joan Murugi Njagi ◽  
Mathew Piero Ngugi
Keyword(s):  
Body Weight ◽  
Learning And Memory ◽  
Spatial Learning ◽  
High Fat Diet ◽  
Spatial Learning And Memory ◽  
Therapeutic Effects ◽  
Memory Retention ◽  
High Fat ◽  
Obesity Index ◽  
Obese Rats

Chronic exposures to high-fat diets are linked to neuropathological changes that culminate in obesity-related cognitive dysfunction and brain alteration. Learning, memory performance, and executive function are the main domains affected by an obesogenic diet. There are limited effective therapies for addressing cognitive deficits. Thus, it is important to identify additional and alternative therapies. In African traditional medicine, Gnidia glauca has putative efficacy in the management of obesity and associated complications. The use of Gnidia glauca is largely based on its long-term traditional use. Its therapeutic application has not been accompanied by sufficient scientific evaluation to validate its use. Therefore, the current study sought to explore the modulatory effects of dichloromethane leaf extracts of Gnidia glauca on cognitive function in the high-fat diet- (HFD-) induced obese rats. Obesity was induced by feeding the rats with prepared HFD and water ad libitum for 6 weeks. The in vivo antiobesity effects were determined by oral administration of G. glauca at dosage levels of 200, 250, and 300 mg/kg body weight in HFD-induced obese rats from the 6th to the 12th weeks. The Lee obesity index was used as a diagnostic criterion of obesity. The Morris water maze was employed to test spatial learning and memory retention in rats. The results indicated that Gnidia glauca showed potent antiobesity effects as indicated in the reduction of body weight and obesity index in extract-treated rats. Moreover, Gnidia glauca exhibited cognitive-enhancing effects in obese rats. The positive influences on cognitive functions might be attributed to the extracts’ phytochemicals that have been suggested to confer protection against obesity-induced oxidative damage, reduction of central inflammation, and increased neurogenesis. The therapeutic effects observed suggest that Gnidia glauca might be an alternative to current medications for the symptomatic complications of obesity, such as learning and memory loss. Further studies are therefore needed to establish its toxicity profiles.

scholarly journals Naloxone Ameliorates Spatial Memory Deficits and Hyperthermia Induced by a Neurotoxic Methamphetamine Regimen in Male Rats

2019 ◽  
Vol 8 ◽  
pp. 1182 ◽  
Author(s):  
Solmaz Khalifeh ◽  
Mehdi Khodamoradi ◽  
Vahid Hajali ◽  
Hamed Ghazvini ◽  
Lelia Eliasy ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Spatial Memory ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Memory Impairment ◽  
Memory Performance ◽  
Poor Performance ◽  
Male Rats ◽  
Spatial Learning And Memory ◽  
Opiate Antagonist

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]

scholarly journals Targeted Reducing of Tauopathy Alleviates Epileptic Seizures and Spatial Memory Impairment in an Optogenetically Inducible Mouse Model of Epilepsy

2021 ◽  
Vol 8 ◽  
Author(s):  
Yang Gao ◽  
Jie Zheng ◽  
Tao Jiang ◽  
Guilin Pi ◽  
Fei Sun ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Epileptic Seizures ◽  
Neuronal Firing ◽  
Spatial Learning And Memory ◽  
Memory Impairments ◽  
Optogenetic Stimulation ◽  
Hippocampal Ca1 ◽  
The Brain

Intracellular deposition of hyperphosphorylated tau has been reported in the brain of epilepsy patients, but its contribution to epileptic seizures and the association with spatial cognitive functions remain unclear. Here, we found that repeated optogenetic stimulation of the excitatory neurons in ventral hippocampal CA1 subset could induce a controllable epileptic seizure in mice. Simultaneously, the mice showed spatial learning and memory deficits with a prominently elevated total tau and phospho-tau levels in the brain. Importantly, selective facilitating tau degradation by using a novel designed proteolysis-targeting chimera named C4 could effectively ameliorate the epileptic seizures with remarkable restoration of neuronal firing activities and improvement of spatial learning and memory functions. These results confirm that abnormal tau accumulation plays a pivotal role in the epileptic seizures and the epilepsy-associated spatial memory impairments, which provides new molecular target for the therapeutics.

scholarly journals A variant of the Morris water task for assessing learning and memory processes in mice

2017 ◽  
Author(s):  
Jogender Mehla ◽  
Jamshid Faraji ◽  
Takashi Saito ◽  
Takaomi C Saido ◽  
Majid H. Mohajerani ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Training Session ◽  
Brain Diseases ◽  
Spatial Learning And Memory ◽  
Second Phase ◽  
Memory Processes ◽  
Morris Water Task ◽  
New Location

AbstractThe Morris water task (MWT) is commonly used to assess rodent spatial learning and memory. Our goal was to develop a 3-phase variant of the hidden goal water task to assess old and new spatial memories acquired in the same context using various measures of spatial learning in C57BL/6 mice. In the first phase, mice were pre-trained to an initially hidden location. The second phase consisted of a massed training session to a new location in the same apparatus and context. The final phase consisted of a competition test between the original and new platform locations. AppNL-G-F/NL-G-F mice, a novel transgenic mouse model for Alzheimer’s disease (AD), were also used as an independent variable to validate this 3-phase variant of MWT. The results of the present study showed that C57 mice acquired and retained both the old and new location representations; however, AppNL-G-F/NL-G-F mice retained a recently acquired spatial memory but did not remember the old location acquired in the same apparatus and context. The results showed that C57 mice can show precise place learning and memory with the right amount of training and acquire and retain multiple spatial memory locations in the same environment whereas this ability was impaired in AppNL-G-F/NL-G-F mice. In the visible platform test, however, all groups of mice showed normal sensorimotor ability and motivation. These findings indicate that this new version of the MWT provides a robust way for assessment of old and new memories in mice. This paradigm could also be exploited to assess manipulations of neural circuits implicated in learning and memory processes as well as for research investigating human brain diseases.

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 ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Learning And Memory ◽  
Fatigue Resistance ◽  
Spatial Learning ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
Apoptotic Pathway ◽  
Apoptosis Pathways ◽  
Pka Pathway

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.

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