scholarly journals Improvement of Learning and Memory in Senescence-Accelerated Mice by S-Allylcysteine in Mature Garlic Extract

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1834
Author(s):  
Masakazu Hashimoto ◽  
Tsuyoshi Nakai ◽  
Teruaki Masutani ◽  
Keiko Unno ◽  
Yukihiro Akao
Keyword(s):  
Learning And Memory ◽  
Brain Function ◽  
Hippocampal Neurons ◽  
Garlic Extract ◽  
Cognitively Impaired ◽  
Calcium Calmodulin Dependent ◽  
Multiple Components ◽  
Dependent Protein ◽  
Senescence Accelerated Mice ◽  
Cultured Hippocampal Neurons

S-allylcysteine (SAC), a major thioallyl compound contained in mature garlic extract (MGE), is known to be a neuroactive compound. This study was designed to investigate the effects of SAC on primary cultured hippocampal neurons and cognitively impaired senescence-accelerated mice prone 10 (SAMP10). Treatment of these neurons with MGE or SAC significantly increased the total neurite length and number of dendrites. SAMP10 mice fed MGE or SAC showed a significant improvement in memory dysfunction in pharmacological behavioral analyses. The decrease of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, N-methyl-d-aspartate (NMDA) receptor, and phosphorylated α-calcium/calmodulin-dependent protein kinase II (CaMKII) in the hippocampal tissue of SAMP10 mice fed MGE or SAC was significantly suppressed, especially in the MGE-fed group. These findings suggest that SAC positively contributes to learning and memory formation, having a beneficial effect on brain function. In addition, multiple components (aside from SAC) contained in MGE could be useful for improving cognitive function by acting as neurotrophic factors.

scholarly journals Calcium-/Calmodulin-Dependent Protein Kinase II (CaMKII) Inhibition Induces Learning and Memory Impairment and Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Jialu Wang ◽  
Xiaoxue Xu ◽  
Wanying Jia ◽  
Dongyi Zhao ◽  
Tomasz Boczek ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Memory Impairment ◽  
Camp Response Element Binding ◽  
Morris Water Maze Test ◽  
Tunel Staining ◽  
Protein Activity ◽  
Calcium Calmodulin Dependent ◽  
Cultured Hippocampal Neurons

Objectives. Inhibition of calcium-/calmodulin- (CaM-) dependent kinase II (CaMKII) is correlated with epilepsy. However, the specific mechanism that underlies learning and memory impairment and neuronal death by CaMKII inhibition remains unclear. Materials and Methods. In this study, KN93, a CaMKII inhibitor, was used to investigate the role of CaMKII during epileptogenesis. We first identified differentially expressed genes (DEGs) in primary cultured hippocampal neurons with or without KN93 treatment using RNA-sequencing. Then, the impairment of learning and memory by KN93-induced CaMKII inhibition was assessed using the Morris water maze test. In addition, Western blotting, immunohistochemistry, and TUNEL staining were performed to determine neuronal death, apoptosis, and the relative signaling pathway. Results. KN93-induced CaMKII inhibition decreased cAMP response element-binding (CREB) protein activity and impaired learning and memory in Wistar and tremor (TRM) rats, an animal model of genetic epilepsy. CaMKII inhibition also induced neuronal death and reactive astrocyte activation in both the Wistar and TRM hippocampi, deregulating mitogen-activated protein kinases. Meanwhile, neuronal death and neuron apoptosis were observed in PC12 and primary cultured hippocampal neurons after exposure to KN93, which was reversed by SP600125, an inhibitor of c-Jun N-terminal kinase (JNK). Conclusions. CaMKII inhibition caused learning and memory impairment and apoptosis, which might be related to dysregulated JNK signaling.

scholarly journals Deficiency of Intellectual Disability-Related Gene Brpf1 Attenuated Hippocampal Excitatory Synaptic Transmission and Impaired Spatial Learning and Memory Ability

2021 ◽  
Vol 9 ◽  
Author(s):  
Weiwei Xian ◽  
Jingli Cao ◽  
Xiangshan Yuan ◽  
Guoxiang Wang ◽  
Qiuyan Jin ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Synaptic Transmission ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurons ◽  
Dendritic Morphology ◽  
Excitatory Synaptic Transmission ◽  
Spatial Learning And Memory ◽  
Memory Ability ◽  
Cultured Hippocampal Neurons

Patients with monoallelic bromodomain and PHD finger-containing protein 1 (BRPF1) mutations showed intellectual disability. The hippocampus has essential roles in learning and memory. Our previous work indicated that Brpf1 was specifically and strongly expressed in the hippocampus from the perinatal period to adulthood. We hypothesized that mouse Brpf1 plays critical roles in the morphology and function of hippocampal neurons, and its deficiency leads to learning and memory deficits. To test this, we performed immunofluorescence, whole-cell patch clamp, and mRNA-Seq on shBrpf1-infected primary cultured hippocampal neurons to study the effect of Brpf1 knockdown on neuronal morphology, electrophysiological characteristics, and gene regulation. In addition, we performed stereotactic injection into adult mouse hippocampus to knock down Brpf1 in vivo and examined the learning and memory ability by Morris water maze. We found that mild knockdown of Brpf1 reduced mEPSC frequency of cultured hippocampal neurons, before any significant changes of dendritic morphology showed. We also found that Brpf1 mild knockdown in the hippocampus showed a decreasing trend on the spatial learning and memory ability of mice. Finally, mRNA-Seq analyses showed that genes related to learning, memory, and synaptic transmission (such as C1ql1, Gpr17, Htr1d, Glra1, Cxcl10, and Grin2a) were dysregulated upon Brpf1 knockdown. Our results showed that Brpf1 mild knockdown attenuated hippocampal excitatory synaptic transmission and reduced spatial learning and memory ability, which helps explain the symptoms of patients with BRPF1 mutations.

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