scholarly journals The Vulnerability of the Developing Brain: Analysis of Highly Expressed Genes in Infant C57BL/6 Mouse Hippocampus in Relation to Phenotypic Annotation Derived From Mutational Studies

2022 ◽  
Vol 16 ◽  
pp. 117793222110627
Author(s):  
Angelica Lindlöf
Keyword(s):  
Animal Studies ◽  
Motor Coordination ◽  
Declarative Memory ◽  
Easy Access ◽  
Hippocampal Damage ◽  
Juvenile Period ◽  
Time Points ◽  
Annotation Data ◽  
Mouse Hippocampus ◽  
Highly Expressed Genes

The hippocampus has been shown to have a major role in learning and memory, but also to participate in the regulation of emotions. However, its specific role(s) in memory is still unclear. Hippocampal damage or dysfunction mainly results in memory issues, especially in the declarative memory but, in animal studies, has also shown to lead to hyperactivity and difficulty in inhibiting responses previously taught. The brain structure is affected in neuropathological disorders, such as Alzheimer’s, epilepsy, and schizophrenia, and also by depression and stress. The hippocampus structure is far from mature at birth and undergoes substantial development throughout infant and juvenile life. The aim of this study was to survey genes highly expressed throughout the postnatal period in mouse hippocampus and which have also been linked to an abnormal phenotype through mutational studies to achieve a greater understanding about hippocampal functions during postnatal development. Publicly available gene expression data from C57BL/6 mouse hippocampus was analyzed; from a total of 5 time points (at postnatal day 1, 10, 15, 21, and 30), 547 genes highly expressed in all of these time points were selected for analysis. Highly expressed genes are considered to be of potential biological importance and appear to be multifunctional, and hence any dysfunction in such a gene will most likely have a large impact on the development of abilities during the postnatal and juvenile period. Phenotypic annotation data downloaded from Mouse Genomic Informatics database were analyzed for these genes, and the results showed that many of them are important for proper embryo development and infant survival, proper growth, and increase in body size, as well as for voluntary movement functions, motor coordination, and balance. The results also indicated an association with seizures that have primarily been characterized by uncontrolled motor activity and the development of proper grooming abilities. The complete list of genes and their phenotypic annotation data have been compiled in a file for easy access.

scholarly journals Cerebellar Development and Plasticity: Perspectives for Motor Coordination Strategies, for Motor Skills, and for Therapy

2005 ◽  
Vol 12 (2-3) ◽  
pp. 153-160 ◽  
Author(s):  
J. D. Swinny ◽  
J. J. L. van der Want ◽  
A. Gramsbergen
Keyword(s):  
Motor Skills ◽  
Animal Studies ◽  
Motor Coordination ◽  
Morphological Development ◽  
Late Development ◽  
Coordination Strategies ◽  
Naturally Occurring ◽  
Temporal And Spatial ◽  
Spatial Identification

The role of the mammalian cerebellum ranges from motor coordination, sensory-motor integration, motor learning, and timing to nonmotor functions such as cognition. In terms of motor function, the development of the cerebellum is of particular interest because animal studies show that the development of the cerebellar cortical circuitry closely parallels motor coordination. Ultrastructural analysis of the morphological development of the cerebellar circuitry, coupled with the temporal and spatial identification of the neurochemical substrates expressed during development, will help to elucidate their roles in the establishment of the cerebellar circuitry and hence motor activity. Furthermore, the convenience of a number of naturally occurring mouse mutations has allowed a functional dissection of the various cellular elements that make up the cerebellar circuitry. This understanding will also help in the approach to possible therapies of pathologies arising during development because tile cerebellum is especially prone to such perturbation because of its late development.

Brain Injury With Prolonged Seizures in Children and Adults

1998 ◽  
Vol 13 (1_suppl) ◽  
pp. S3-S6 ◽  
Author(s):  
Solomon L. Moshé
Keyword(s):  
Temporal Lobe ◽  
Animal Studies ◽  
Science Studies ◽  
Hippocampal Sclerosis ◽  
Epidemiologic Studies ◽  
Late Childhood ◽  
Hippocampal Damage ◽  
Adult Rats ◽  
Spontaneous Seizures ◽  
The Brain

Some retrospective studies have suggested that there is a relationship between seizures early in life and the development of hippocampal damage (mesial temporal lobe hippocampal sclerosis) leading to intractable temporal lobe epilepsy in late childhood or adulthood. Recent prospective epidemiologic studies have not confirmed such a relationship, however, and many questions remain. Some of these questions are being addressed by animal studies. In adult rats, experimental seizures produce varying degrees of hippocampal damage and subsequent spontaneous seizures; the older the rat, the greater the hippocampal injury. The preponderance of available data indicate that such seizure-induced hippocampal damage may not occur in normally developing rats up to a certain age that may correspond to late childhood in humans. However, if the brain is already compromised, seizures early in life may produce hippocampal damage, depending on the nature of the initial lesion. Thus, the consequences of seizures appear to be age and etiology specific. Additional clinical and basic science studies are needed to clarify the neurobiology of seizure-induced hippocampal damage in children. (J Child Neurol 1998;13(Suppl 1):S3-S6).

scholarly journals Neurobehavioral, Neuromotor, and Neurocognitive Effects in Agricultural Workers and Their Children Exposed to Pyrethroid Pesticides: A Review

2021 ◽  
Vol 15 ◽  
Author(s):  
Boris Lucero ◽  
María Teresa Muñoz-Quezada
Keyword(s):  
Occupational Exposure ◽  
Animal Studies ◽  
English Language ◽  
Motor Coordination ◽  
Insect Pests ◽  
Scientific Evidence ◽  
Agricultural Workers ◽  
Simultaneous Exposure ◽  
Neurobehavioral Performance ◽  
Pyrethroid Pesticides

In recent years, pyrethroids have emerged as a less toxic alternative to eliminate insect pests. However, some animal studies and studies with children show that these pesticides are toxic and lead to neurobehavioral effects similar to other pesticides, such as organophosphates. The purpose of this review was to systematize the epidemiological scientific evidence about the neurobehavioral, neuromotor, and neurocognitive effects in agricultural workers and their children exposed to pyrethroid pesticides. We conducted two searches (with different terms) in PubMed and Scopus databases, including articles in Spanish and English language on the effects of occupational exposure to pyrethroid pesticides associated with neurobehavioral, neuromotor, and neurocognitive functioning of agricultural workers and their children. There were no filters by year, and the search included studies till march 2021. To develop the search, we followed the recommendations contained in the PRISMA guidelines and the PICO strategy. The results show that in 66.6% of the studies reviewed (8 of 12 studies), agricultural workers or their children occupationally exposed to pyrethroid pesticides have a higher risk of presenting difficulties in their neurocognitive, neuromotor, or neurobehavioral performance, mainly associated with attention, processing speed (linked to hand-eye coordination), and motor coordination. There are still few studies that address this issue. However, the quality of most of the research conducted (83% intermediate or high quality) confirms the risk for neurobehavioral health in agricultural workers due to occupational exposure to pyrethroids. More research is required evaluating the exposure to pyrethroids, including biomarkers and validated neurobehavioral and neuromotor tests, in addition to evaluating the effect of simultaneous exposure to other hazardous pesticides. Assuming that the use of pyrethroids is increasing considerably and faster than the scientific evidence, it is suggested as a precautionary principle to regulate, more strictly, the sale of pyrethroids and other pesticides.

Clinical analgesia correlates with decline in temporal summation in response to remifentanil infusion in patients with chronic neuropathic (radicular) pain

2016 ◽  
Vol 12 (4) ◽  
pp. 251
Author(s):  
Erica Suzan, PhD ◽  
Ayelet Midbari, MD ◽  
Dorit Pud, PhD ◽  
Salim Hadad, PhD ◽  
Elon Eisenberg, MD
Keyword(s):  
Pain Intensity ◽  
Animal Studies ◽  
Temporal Summation ◽  
Tertiary Care ◽  
Radicular Pain ◽  
Rank Test ◽  
Time Points ◽  
Clinical Pain ◽  
The Difference ◽  
Two Parameters

Background: Animal studies have shown that in addition to their antinociceptive effects, opioids have attenuated the electrophysiological “wind-up” phenomenon. Although effects of opioids on clinical pain and on temporal summation (TS), the human correlatives of this phenomenon, have been tested repeatedly, correlations between these two parameters have not been reported so far.Objectives: To search for possible correlations between the effects of remifentanil on clinical pain intensity and on the magnitude of TS in patients with chronic pain.Design: A single-blinded prospective study.Setting: A tertiary care pain clinic.Patients: Thirty-one patients (24 men) with chronic lumbar (radicular) neuropathic pain.Intervention: Intervenous administration of saline followed by remifentanil infusions.Main Outcome Measures: Clinical pain intensity and thermal TS measured at baseline, during infusion of each drug and 20 minutes after termination of remifentnail infusion.Results: Friedman test revealed statistically significant differences in the magnitudes of both clinical pain intensity and TS (χ2(3) = 73, p < 0.001 and χ2(3) = 11.38, p = 0.01, respectively). Post hoc analysis (Wilcoxon signed-rank test) showed significant differences between clinical pain intensities measured at all time points but significant reductions in the magnitudes of TS were found only during remifentanil compared to baseline (p = 0.014) and to saline (p = 0.019). The difference in clinical pain between saline and remifentanil positively correlated with the difference in TS measured at the same time points (Spearman's test; r = 0.444, p = 0.012).Conclusions: These results point to a possible causative relationship between TS and opioid analgesia.

Multiple memory systems

2018 ◽  
Author(s):  
Richard J. Beninger
Keyword(s):  
Declarative Memory ◽  
Dorsal Striatum ◽  
Recognition Task ◽  
Memory Systems ◽  
Learning Task ◽  
Hippocampal Damage ◽  
Incentive Learning ◽  
Multiple Memory Systems ◽  
Stimulus Response ◽  
Memory Rats

Multiple memory systems describes how memories can be declarative or non-declarative; incentive learning produces one type of non-declarative memory. Patients with bilateral hippocampal damage have declarative memory deficits (amnesia) but intact non-declarative memory; patients with striatal dysfunction, for example, Parkinson’s patients who lose striatal dopamine have impaired incentive learning but intact declarative memory. Rats with lesions of the fornix (hippocampal output pathway), but not lesions of the dorsal striatum, have impaired spatial (declarative) memory; rats with lesions of the dorsal striatum, but not fornix, have impaired stimulus–response memory that relies heavily on incentive learning. These memory systems possibly inhibit one another to control responding: in rats, a group that received fornix lesions and had impaired spatial learning did better on an incentive task; in humans, hippocampus damage was associated with improvement on an incentive learning task and striatal damage was associated with increased involvement of the hippocampus in a route-recognition task.

scholarly journals 0100 Effect of Naps on Preschoolers’ Consolidation of an Emotional Storybook

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A40-A40
Author(s):  
J F Holmes ◽  
M K Deighan ◽  
N W Miranda ◽  
G M Mason ◽  
R M Spencer
Keyword(s):  
Preschool Children ◽  
Memory Consolidation ◽  
Declarative Memory ◽  
Memory Performance ◽  
Emotional Memory ◽  
Multiple Choice Questions ◽  
Time Points ◽  
Sleep Physiology ◽  
Emotional Events ◽  
Time Point

Abstract Introduction Naps are known to benefit emotional memory consolidation in preschoolers, though improvement is not evident until the following day. The mechanisms by which naps aid emotional memory, and how they differ from those facilitating more neutral declarative memory consolidation, are currently unknown. In this study, we used an emotional storybook task to assess change in memory for emotionally salient vs. neutral events across a nap and overnight sleep. PSG was included to explore sleep physiology correlates. Methods Preschool children (n = 9; Mage= 43.2 months) were read a novel storybook featuring negative and neutral events. Memory of story events was probed through sets of multiple-choice questions and assessed at three time points: immediately following the story, following a nap or equivalent wake period (within-subject; counterbalanced; separated by ~1 week), and 24h post-encoding. PSG was recorded during the nap period and both subsequent overnight sleep bouts. Results Memory performance across time points was assessed via change scores. Recall of story events did not differ between conditions from immediate to post-nap/wake assessment. When probed the following morning, children better remembered events when a nap took place the day prior (F(1,7) = 8.848, p=.021). This delayed nap benefit correlated with time spent in NREM2 during the nap (r=.91, p=.017). No differences were found between recall of negative vs. neutral events at any time point or between conditions. Conclusion Our results show a delayed benefit of napping on recall of a storybook, though at present no preference for emotional events is seen. Time spent in NREM2 during the nap was strongly associated with our finding, likely reflecting the declarative memory benefits conferred from this stage. Further analyses will include overnight sleep physiology to explore differential enhancement between event types, and possible interactions with nap microstructure. Support This work was supported by NIH R01 HL111695.

scholarly journals Intranasal Delivery of miR-146a Mimics Delayed Seizure Onset in the Lithium-Pilocarpine Mouse Model

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Hua Tao ◽  
Jianghao Zhao ◽  
Tingting Liu ◽  
Yujie Cai ◽  
Xu Zhou ◽  
...  
Keyword(s):  
Mouse Model ◽  
Molecular Target ◽  
Hippocampal Damage ◽  
Intranasal Delivery ◽  
Seizure Onset ◽  
Time Points ◽  
Novel Treatments ◽  
Anti Inflammatory ◽  
Pilocarpine Injection

Unveiling the key mechanism of temporal lobe epilepsy (TLE) for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp.). After intranasal delivery of miR-146a mimics (30 min before pilocarpine injection), the percent of animals with no induced seizures increased by 6.7%, the latency to generalized convulsions was extended, and seizure severity was reduced. Additionally, hippocampal damage was alleviated. While the relative miR-146a levels significantly increased, the expression of its target mRNAs (IRAK-1 and TRAF-6) and typical inflammatory modulators (NF-κB, TNF-α, IL-1β, and IL-6) decreased, supporting an anti-inflammatory role of miR-146a via the TLR pathway. This study is the first to demonstrate that intranasal delivery of miR-146a mimics can improve seizure onset and hippocampal damage in the acute phase of lithium-pilocarpine-induced seizures, which provides inflammation-based clues for the development of novel TLE treatments.

scholarly journals Methods detecting rhythmic gene expression are biologically relevant only for strong signal

2019 ◽  
Author(s):  
David Laloum ◽  
Marc Robinson-Rechavi
Keyword(s):  
Gene Expression ◽  
Reference Group ◽  
Biologically Relevant ◽  
Rna Molecules ◽  
Time Points ◽  
Rhythmic Expression ◽  
Large Sets ◽  
Naive Method ◽  
Highly Expressed Genes ◽  
Rhythmic Gene

AbstractThe nycthemeral transcriptome embodies all genes displaying a rhythmic variation of their mRNAs periodically every 24 hours, including but not restricted to circadian genes. In this study, we show that the nycthemeral rhythmicity at the gene expression level is biologically functional and that this functionality is more conserved between orthologous genes than between random genes. We used this conservation of the rhythmic expression to assess the ability of seven methods (ARSER, Lomb Scargle, RAIN, JTK, empirical-JTK, GeneCycle, and meta2d) to detect rhythmic signal in gene expression. We have contrasted them to a naive method, not based on rhythmic parameters. By taking into account the tissue-specificity of rhythmic gene expression and different species comparisons, we show that no method is strongly favored. The results show that these methods designed for rhythm detection, in addition to having quite similar performances, are consistent only among genes with a strong rhythm signal. Rhythmic genes defined with a standard p-value threshold of 0.01 for instance, could include genes whose rhythmicity is biologically irrelevant. Although these results were dependent on the datasets used and the evolutionary distance between the species compared, we call for caution about the results of studies reporting or using large sets of rhythmic genes. Furthermore, given the analysis of the behaviors of the methods on real and randomized data, we recommend using primarily ARS, empJTK, or GeneCycle, which verify expectations of a classical distribution of p-values. Experimental design should also take into account the circumstances under which the methods seem more efficient, such as giving priority to biological replicates over the number of time-points, or to the number of time-points over the quality of the technique (microarray vs RNAseq). GeneCycle, and to a lesser extent empirical-JTK, might be the most robust method when applied to weakly informative datasets. Finally, our analyzes suggest that rhythmic genes are mainly highly expressed genes.Author SummaryTo be active, genes have to be transcribed to RNA. For some genes, the transcription rate follows a circadian rhythm with a periodicity of approximately 24 hours; we call these genes “rhythmic”. In this study, we compared methods designed to detect rhythmic genes in gene expression data. The data are measures of the number of RNA molecules for each gene, given at several time-points, usually spaced 2 to 4 hours, over one or several periods of 24 hours. There are many such methods, but it is not known which ones work best to detect genes whose rhythmic expression is biologically functional. We compared these methods using a reference group of evolutionarily conserved rhythmic genes. We compared data from baboon, mouse, rat, zebrafish, fly, and mosquitoes. Surprisingly, no method was particularly effective. Furthermore, we found that only very strong rhythmic signals were relevant with each method. More precisely, when we use a usual cut-off to define rhythmic genes, the group of genes considered as rhythmic contains many genes whose rhythmicity cannot be confirmed to be biologically relevant. We also show that rhythmic genes mainly contain highly expressed genes. Finally, based on our results, we provide recommendations on which methods to use and how, and suggestions for future experimental designs.

scholarly journals ShinyAIM: Shiny-based Application of Interactive Manhattan Plots for Longitudinal Genome-Wide Association Studies

2018 ◽  
Author(s):  
Waseem Hussain ◽  
Malachy Campbell ◽  
Harkamal Walia ◽  
Gota Morota
Keyword(s):  
Data Visualization ◽  
Association Studies ◽  
Genome Wide Association ◽  
Easy Access ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Phenotypic Data ◽  
Online Application ◽  
Time Points ◽  
Genome Wide

AbstractDue to advancements in sensor-based, non-destructive phenotyping platforms, researchers are increasingly collecting data with higher temporal resolution. These phenotypes collected over several time points are cataloged as longitudinal traits and used for genome-wide association studies (GWAS). Longitudinal GWAS typically yield a large number of output files, posing a significant challenge for data interpretation and visualization. Efficient, dynamic, and integrative data visualization tools are essential for the interpretation of longitudinal GWAS results for biologists but are not widely available to the community. We have developed a flexible and user-friendly Shiny-based online application, ShinyAIM, to dynamically view and interpret temporal GWAS results. The main features of the application include (i) an interactive Manhattan plots for single time points, (ii) a grid plot to view Manhattan plots for all time points simultaneously, (iii) dynamic scatter plots for p-value-filtered selected markers to investigate co-localized genomic regions across time points, (iv) and interactive phenotypic data visualization to capture variation and trends in phenotypes. The application is written entirely in the R language and can be used with limited programming experience. ShinyAIM is deployed online as a Shiny web server application at https://chikudaisei.shinyapps.io/shinyaim/, enabling easy access for users without installation. The application can also be launched on the local machine in RStudio.

scholarly journals A Dried Yeast Fermentate Prevents and Reduces Inflammation in Two Separate Experimental Immune Models

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Malkanthi Evans ◽  
Stuart Reeves ◽  
Larry E. Robinson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Clinical Trials ◽  
Animal Studies ◽  
Randomized Trials ◽  
Autoimmune Arthritis ◽  
Control Mechanisms ◽  
Arthritis Model ◽  
Time Points ◽  
Seasonal Allergies

Diverse and significant benefits against cold/flu symptoms and seasonal allergies have been observed with a dried fermentate (DF) derived fromSaccharomyces cerevisiae(EpiCor) in multiple published randomized trials. To determine if DF may influence other immune conditions, two separate animal studies were conducted. Study 1 examined the ability of DF to prevent or reduce inflammation when given orally for 14 days to rats prior to receiving 1% carrageenan (localized inflammation model). DF significantly (P<0.05) reduced swelling at all time points (1, 2, 3, 6, 12, and 24 hours) versus the control. Edema severity and PGE2 levels were reduced by approximately 50% and 25% (P<0.05), respectively. Study 2 examined the ability of DF to treat established inflammation induced by type-2 collagen in mice over 4 weeks (autoimmune arthritis model). Significantly reduced arthritis scores, antibody response to type-2 collagen, and interferon-gamma levels were observed compared to controls (all parametersP<0.05). DF favorably impacts multiple acute and potentially chronic immunologic inflammatory control mechanisms and should be further tested in clinical trials.

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