Overexpression of Kcnmb2 in Dorsal CA1 of Offspring Mice Rescues Hippocampal Dysfunction Caused by a Methyl Donor-Rich Paternal Diet

Yu, Ming; Guo, Li; Li, Nan; Henzel, Kristin S.; Gu, Huating; Ran, Xiufang; Sun, Wei; Liu, Shuai; Lu, Yingchang; Ehninger, Dan; Zhou, Yu

doi:10.3389/fncel.2018.00360

Cited by 13 publications

(9 citation statements)

References 49 publications

(72 reference statements)

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“…The KCNMB2 gene has been associated with suicidal ideation in US military veterans (Kimbrel et al , 2018) and may be related to depression, which is common in the elderly. Further, when KCNMB2 is overexpressed in the hippocampus of mice, it rescues memory deficits (Yu et al , 2018). More work is required to enable better understanding and identification of the molecular pathways involved in LATE.…”

Section: Introductionmentioning

confidence: 99%

Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report

Nelson

Dickson

Trojanowski

et al. 2019

Brain

992

1,035

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Nelson et al. describe a recently recognized brain disorder that mimics the clinical features of Alzheimer’s disease: L imbic-predominant A ge-related T DP-43 E ncephalopathy (LATE). They review the literature and present consensus-based recommendations of an international, multidisciplinary working group, providing guidelines for diagnosis and staging of LATE neuropathological changes.

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Section: Introductionmentioning

confidence: 99%

Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report

Nelson

Dickson

Trojanowski

et al. 2019

Brain

992

1,035

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“…Ca 2+ activated K + channels: these channels use changes in Ca 2+ levels to regulate membrane conductance of K + (i.e., the entry and exit of the K ion) [ 76 ]. They are present in glial cells signaling [ 77 ] and also in the brain. A recent study using a mice-based animal model showed a correlation between the alteration of this gene and a reduced inhibitory synaptic transmission, as well as decreased neural intrinsic excitability in the mice [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

Minor Allele Frequencies and Molecular Pathways Differences for SNPs Associated with Amyotrophic Lateral Sclerosis in Subjects Participating in the UKBB and 1000 Genomes Project

D’Antona

Bertoli

Castiglioni

et al. 2021

JCM

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Amyotrophic lateral sclerosis (ALS) is a complex disease with a late onset and is characterized by the progressive loss of muscular and respiratory functions. Although recent studies have partially elucidated ALS’s mechanisms, many questions remain such as what the most important molecular pathways involved in ALS are and why there is such a large difference in ALS onset among different populations. In this study, we addressed this issue with a bioinformatics approach, using the United Kingdom Biobank (UKBB) and the European 1000 Genomes Project (1KG) in order to analyze the most ALS-representative single nucleotide polymorphisms (SNPs) that differ for minor allele frequency (MAF) between the United Kingdom population and some European populations including Finnish in Finland, Iberian population in Spain, and Tuscans in Italy. We found 84 SNPs associated with 46 genes that are involved in different pathways including: “Ca2+ activated K+ channels”, “cGMP effects”, ”Nitric oxide stimulates guanylate cyclase”, “Proton/oligopeptide cotransporters”, and “Signaling by MAPK mutants”. In addition, we revealed that 83% of the 84 SNPs can alter transcription factor-motives binding sites of 224 genes implicated in “Regulation of beta-cell development”, “Transcription-al regulation by RUNX3”, “Transcriptional regulation of pluripotent stem cells”, and “FOXO-mediated transcription of cell death genes”. In conclusion, the genes and pathways analyzed could explain the cause of the difference of ALS onset.

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“…Consequently, they are involved in learning and memory (Raffaelli et al 2004;Lee and Cui 2010). The BK channel beta subunit 2, encoded by Kcnmb2, plays a role in the inactivation of BK channels (Yu et al 2018), and methyl donors have a transgenerational effect, specifically by altering Kcnmb2 methylation, a phenomenon that decreases its expression (Ryan et al 2018). These changes may be involved with our findings, where some neurotransmitters are increased.…”

Section: Discussionmentioning

confidence: 99%

Paternal exposure to excessive methionine altered behavior and neurochemical activities in zebrafish offspring

et al. 2021

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An increase in plasma l-methionine (Met) levels, even if transitory, can cause important toxicological alterations in the affected individuals. Met is essential in the regulation of epigenetic mechanisms and its influence on the subsequent generation has been investigated. However, few studies have explored the influence of a temporary increase in Met levels in parents on their offspring. This study evaluated the behavioral and neurochemical effects of parental exposure to high Met concentration (3 mM) in zebrafish offspring. Adult zebrafish were exposed to Met for 7 days, maintained for additional 7 days in tanks that contained only water, and then used for breeding. The offspring obtained from these fish (F1) were tested in this study. During the early stages of offspring development, morphology, heart rate, survival, locomotion, and anxiety-like behavior were assessed. When these animals reached the adult stage, locomotion, anxiety, aggression, social interaction, memory, oxidative stress, and levels of amino acids and neurotransmitters were analyzed. F1 larvae Met group presented an increase in the distance and mean speed when compared to the control group. F1 adult Met group showed decreased anxiety-like behavior and locomotion. An increase in reactive oxygen species was also observed in the F1 adult Met group whereas lipid peroxidation and antioxidant enzymes did not change when compared to the control group. Dopamine, serotonin, glutamate, and glutathione levels were increased in the F1 adult Met group. Taken together, our data show that even a transient increase in Met in parents can cause behavioral and neurochemical changes in the offspring, promoting transgenerational effects.

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Overexpression of Kcnmb2 in Dorsal CA1 of Offspring Mice Rescues Hippocampal Dysfunction Caused by a Methyl Donor-Rich Paternal Diet

Cited by 13 publications

References 49 publications

Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report

Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report

Minor Allele Frequencies and Molecular Pathways Differences for SNPs Associated with Amyotrophic Lateral Sclerosis in Subjects Participating in the UKBB and 1000 Genomes Project

Paternal exposure to excessive methionine altered behavior and neurochemical activities in zebrafish offspring

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