scholarly journals Neuronal dysfunctions and cognitive deficits in a multi-hit rat model following cumulative effects of early life stressors

2020 ◽  
Author(s):  
Tiyasha Sarkar ◽  
Nisha Patro ◽  
Ishan Kumar Patro
Keyword(s):  
Spatial Memory ◽  
Rat Model ◽  
Neurological Disorders ◽  
Early Life ◽  
Bacterial Infections ◽  
Later Life ◽  
Poly I:C ◽  
Life Stressors ◽  
Memory Impairments ◽  
Cellular Apoptosis

AbstractPerinatal protein malnourishment is a leading cause for mental and physical retardation in children with poor socioeconomic conditions. Such malnourished children are vulnerable to additional stressors, that may synergistically act to cause neurological disorders at adulthood. In this study, the above mentioned condition is mimicked via a multi-hit rat model in which pups born to protein malnourished mothers (LP) were co-injected with polyinosinic:polycytidylic acid (Poly I:C; viral mimetic) at Postnatal day (PND) 3 and lipopolysaccharide (LPS; bacterial mimetic) at PND 9. Individual exposure of Poly I:C and LPS was also given to LP pups to correlate chronicity of stress. Similar treatments were also given to control pups. Hippocampal cellular apoptosis, β III tubulin catastrophe, altered neuronal profiling and spatial memory impairments were assessed at PND 180, using specific immunohistochemical markers (active caspase 3, β III tubulin, doublecortin), Golgi studies and cognitive mazes (Morris Water Maze and T maze). Increase in cellular apoptosis, loss of dendritic arborization and spatial memory impairments were higher in multi-hit group, than the single-hit groups. Such impairments observed due to multi-hit stress, mimic conditions similar to many neurological disorders and hence it is hypothesized that later life neurological disorders might be an outcome of multiple early life hits.Summary StatementThis study is first of its kind which practically studies the combined effects of major early life stressors like protein malnourishment, viral and bacterial infections on the nervous system.

scholarly journals Neuronal changes and cognitive deficits in a multi-hit rat model following cumulative impact of early life stressors

Biology Open ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. bio054130 ◽  
Author(s):  
Tiyasha Sarkar ◽  
Nisha Patro ◽  
Ishan Kumar Patro
Keyword(s):  
Spatial Memory ◽  
Rat Model ◽  
Neurological Disorders ◽  
Early Life ◽  
Later Life ◽  
Poly I:C ◽  
Cumulative Impact ◽  
Memory Impairments ◽  
Immunohistochemical Markers ◽  
Cellular Apoptosis

ABSTRACTPerinatal protein malnourishment (LP) is a leading cause for mental and physical retardation in children from poor socioeconomic conditions. Such malnourished children are vulnerable to additional stressors that may synergistically act to cause neurological disorders in adulthood. In this study, the above mentioned condition was mimicked via a multi-hit rat model in which pups born to LP mothers were co-injected with polyinosinic:polycytidylic acid (Poly I:C; viral mimetic) at postnatal day (PND) 3 and lipopolysaccharide (LPS; bacterial mimetic) at PND 9. Individual exposure of Poly I:C and LPS was also given to LP pups to correlate chronicity of stress. Similar treatments were also given to control pups. Hippocampal cellular apoptosis, β III tubulin catastrophe, altered neuronal profiling and spatial memory impairments were assessed at PND 180, using specific immunohistochemical markers (active caspase 3, β III tubulin, doublecortin), golgi studies and cognitive mazes (Morris water maze and T maze). Increase in cellular apoptosis, loss of dendritic arborization and spatial memory impairments were higher in the multi-hit group, than the single-hit groups. Such impairments observed due to multi-hit stress mimicked conditions similar to many neurological disorders and hence, it is hypothesized that later life neurological disorders might be an outcome of multiple early life hits.This article has an associated First Person interview with the first author of the paper.

scholarly journals Poly (I:C) Exposure in Early Life Alters Methylation of DNA and Acetylation of Histone at Synaptic Plasticity Gene Promoter in Developing Rat Brain Leading to Memory Impairment

2019 ◽  
Vol 26 (3-4) ◽  
pp. 35-41
Author(s):  
Meghraj Singh Baghel ◽  
Brijendra Singh ◽  
Nisha Patro ◽  
Vinay Kumar Khanna ◽  
Ishan Kumar Patro ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Early Life ◽  
Memory Impairment ◽  
Viral Infections ◽  
Gene Promoter ◽  
Later Life ◽  
Poly I:C ◽  
Normal Brain ◽  
Gene Promoters ◽  
Methylation Of Dna

Background: Exposure to adverse environmental conditions such as toxic chemicals, viral infections, and even stress during pregnancy or early life may disrupt the development of normal brain and its functioning leading to incidence of neurodevelopmental disorders at later stages of life. Recently, we reported that poly (I:C) exposure altered synaptic plasticity protein level and impaired memory through activation of microglia cells. Purpose: As epigenetic modifications are involved in memory formation, we have studied methylation of DNA and acetylation of histone at promoters of synaptic plasticity genes in the brain of rats exposed to poly (I:C) during early life. Methods: One dose of poly (I:C) (5 mg/kg bw) was intraperitoneally injected to rat pups on postnatal seventh day. A set of pups exposed to vehicle was included as control. In order to assess methylation of DNA and acetylation of histone at synaptic plasticity gene promoter, we performed qPCR after methylated DNA immunoprecipitation and chromatin immunoprecipitation. Results: Poly (I:C) exposure reduced the level of 5-methylcytosine (5mC) at synaptic plasticity gene ( bdnf, arc, and egr1) promoters in the frontal cortex (FC) and hippocampus of 3-week rats, although increased it later in both regions of 12-week rats as compared to respective controls. On contrary, poly (I:C) exposure enhanced acetylation of histone H3K9 (H3K9Ac) at promoters of these genes in both regions of 3-week rats but decreased in 12-week rats. Conclusion: Poly (I:C) exposure altered 5mC and H3K9Ac at synaptic plasticity gene promoters resulting in memory impairment of rats at later life.

scholarly journals Spatial memory impairments in a prediabetic rat model

Neuroscience ◽  
2013 ◽  
Vol 250 ◽  
pp. 565-577 ◽  
Author(s):  
E. Soares ◽  
R.D. Prediger ◽  
S. Nunes ◽  
A.A. Castro ◽  
S.D. Viana ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Rat Model ◽  
Memory Impairments

scholarly journals Short-term block of CRH receptor in adults mitigates age-related memory impairments provoked by early-life adversity

2019 ◽  
Author(s):  
Annabel K. Short ◽  
Pamela M. Maras ◽  
Aidan L. Pham ◽  
Autumn S. Ivy ◽  
Tallie Z. Baram
Keyword(s):  
Spatial Memory ◽  
Early Life ◽  
Middle Age ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Male Rats ◽  
Sensitive Period ◽  
Early Life Adversity ◽  
Memory Impairments ◽  
Age Related

AbstractIn humans, early-life adversity (ELA) is associated with impairments in learning and memory that may emerge later in life. In rodent models, ELA directly impacts hippocampal neuron structure and connectivity with progressive deficits in long-term potentiation and spatial memory function. Previous work has demonstrated that augmented release and actions of the stress-activated neuropeptide, CRH, contribute to the deleterious effects of ELA on hippocampal structure and memory-function. Early-life adversity increases CRH production and levels, and blocking CRH receptor type 1 (CRHR1) within the hippocampus immediately following adversity prevented the memory and LTP problems caused by ELA. Here we queried if blocking CRHR1 during adulthood ameliorates the adverse impact of ELA on memory in middle age. Blocking CRHR1 for a week in two month old male rats prevented ELA-induced deficits in object recognition memory that emerge during middle age. The intervention failed to mitigate the reduction of spatial memory at 4 and 8 months, but restored hippocampus-dependent location memory in ELA-experiencing rats during middle age (12 months of age).Notably, neither ELA nor blocking CRHR1 influenced anxiety- or depression-related behaviors These findings suggest a sensitive period during which interventions can fully prevent long-lasting effects of ELA, yet indicate that interventions later in life offer significant benefits.

scholarly journals First person – Tiyasha Sarkar

Biology Open ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. bio056267
Keyword(s):  
Cognitive Deficits ◽  
Early Life ◽  
Later Life ◽  
Early Career ◽  
Life Stressors ◽  
First Person ◽  
Cumulative Impact ◽  
Early Career Researchers ◽  
Model Following ◽  
Selection Of

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Tiyasha Sarkar is first author on ‘Neuronal changes and cognitive deficits in a multi-hit rat model following cumulative impact of early life stressors’, published in BiO. Tiyasha is a PhD scholar in the lab of Professor Ishan Kumar Patro at the School of Studies in Neuroscience, Jiwaji University Gwalior, Madhya Pradesh, India, investigating the correlation between multiple early life stressors and later life neurological disorders.

scholarly journals Early Origins of Body Mass in Later Life: Examining Childhood Risks and Adult Pathways

2021 ◽  
pp. 002214652110054
Author(s):  
Sarah A. Mustillo ◽  
Miao Li ◽  
Patricia Morton ◽  
Kenneth F. Ferraro
Keyword(s):  
Physical Activity ◽  
Body Mass ◽  
Health Risks ◽  
Early Life ◽  
Life Experiences ◽  
Later Life ◽  
Childhood Experiences ◽  
Older Adulthood ◽  
Early Life Exposure ◽  
Nationally Representative

Prior research reveals that negative early-life experiences play a major role in the development of obesity in later life, but few studies identify mechanisms that alter the lifetime risk of obesity. This study examines the influence of negative childhood experiences on body mass index (BMI) and obesity (BMI ≥30) during older adulthood and the psychosocial and behavioral pathways involved. Using a nationally representative sample, we examine the influence of cumulative misfortune as well as five separate domains of misfortune on BMI and obesity. Results show that four of the five domains are associated with BMI and obesity either directly, indirectly, or both. The influence of cumulative misfortune on the outcomes is mediated by three adult factors: socioeconomic status, depressive symptoms, and physical activity. The mediators identified here provide targets for intervention among older adults to help offset the health risks of excess BMI attributable of early-life exposure to misfortune.

scholarly journals Levels of Predominant Intestinal Microorganisms in 1 Month-Old Full-Term Babies and Weight Gain During the First Year of Life

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2412
Author(s):  
Sonia González ◽  
Marta Selma-Royo ◽  
Silvia Arboleya ◽  
Cecilia Martínez-Costa ◽  
Gonzalo Solís ◽  
...  
Keyword(s):  
Weight Gain ◽  
Gut Microbiota ◽  
Early Life ◽  
Later Life ◽  
Full Term ◽  
First Year ◽  
Term Infants ◽  
Term Newborns ◽  
Infant Weight Gain ◽  
First Year Of Life

The early life gut microbiota has been reported to be involved in neonatal weight gain and later infant growth. Therefore, this early microbiota may constitute a target for the promotion of healthy neonatal growth and development with potential consequences for later life. Unfortunately, we are still far from understanding the association between neonatal microbiota and weight gain and growth. In this context, we evaluated the relationship between early microbiota and weight in a cohort of full-term infants. The absolute levels of specific fecal microorganisms were determined in 88 vaginally delivered and 36 C-section-delivered full-term newborns at 1 month of age and their growth up to 12 months of age. We observed statistically significant associations between the levels of some early life gut microbes and infant weight gain during the first year of life. Classifying the infants into tertiles according to their Staphylococcus levels at 1 month of age allowed us to observe a significantly lower weight at 12 months of life in the C-section-delivered infants from the highest tertile. Univariate and multivariate models pointed out associations between the levels of some fecal microorganisms at 1 month of age and weight gain at 6 and 12 months. Interestingly, these associations were different in vaginally and C-section-delivered babies. A significant direct association between Staphylococcus and weight gain at 1 month of life was observed in vaginally delivered babies, whereas in C-section-delivered infants, lower Bacteroides levels at 1 month were associated with higher later weight gain (at 6 and 12 months). Our results indicate an association between the gut microbiota and weight gain in early life and highlight potential microbial predictors for later weight gain.

scholarly journals Association between early bronchiolitis and the development of childhood asthma: a meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e043956
Author(s):  
Guizuo Wang ◽  
Dong Han ◽  
Zhengdong Jiang ◽  
Manxiang Li ◽  
Shumei Yang ◽  
...  
Keyword(s):  
Early Life ◽  
Fixed Effects ◽  
Late Onset ◽  
Meta Analysis ◽  
Later Life ◽  
Analysis Data ◽  
Fixed Effects Model ◽  
Case Control Studies ◽  
Increased Risk ◽  
Registration Number

ObjectiveEarly life bronchiolitis has been hypothesised to be associated with the subsequent risk of persistent wheezing or asthma. However, the link remains controversial. The objective of our study was to evaluate the association between bronchiolitis before 2 years of age and the late-onset wheezing/asthma.DesignSystematic review and meta-analysis.MethodsPubMed, Embase and Web of Science databases were systematically searched for studies published between 1955 and January 2020. Meanwhile, we also checked through the reference lists of relevant articles to see whether these references included reports of other studies that might be eligible for the review. Cohort and case–control studies assessing the association between early-life bronchiolitis and late-onset wheezing/asthma were included in this meta-analysis. Data were extracted by two independent reviewers. Results were pooled using a random-effects model or fixed-effects model according to the heterogeneity among studies.Results32 original articles with 292 844 participants, which met the criteria, were included in this meta-analysis. Bronchiolitis before 2 years of age was associated with an increased risk of subsequent wheezing/asthma (relative risk=2.46, 95% CI 2.14 to 2.82, p<0.001). After categorising studies into different groups based on age at the end of follow-up, geographical region and study quality, the association still remained significant.ConclusionsThe meta-analysis indicates an association between bronchiolitis before 2 years of age and the wheezing/asthma in later life. Well-designed and highly standardised prospective studies that better address bias due to potential confounding factors are needed to validate the risk identified in our meta-analysis.PROSPERO registration numberCRD42018089453.

scholarly journals Body size throughout the life-course and incident benign prostatic hyperplasia-related outcomes and nocturia

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Saira Khan ◽  
K. Y. Wolin ◽  
R. Pakpahan ◽  
R. L. Grubb ◽  
G. A. Colditz ◽  
...  
Keyword(s):  
Body Size ◽  
Benign Prostatic Hyperplasia ◽  
Life Course ◽  
Early Life ◽  
Prostate Volume ◽  
Late Life ◽  
Later Life ◽  
Normal Weight ◽  
Prostatic Hyperplasia ◽  
The Life Course

Abstract Background Existing evidence suggests that there is an association between body size and prevalent Benign Prostatic Hyperplasia (BPH)-related outcomes and nocturia. However, there is limited evidence on the association between body size throughout the life-course and incident BPH-related outcomes. Methods Our study population consisted of men without histories of prostate cancer, BPH-related outcomes, or nocturia in the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (n = 4710). Associations for body size in early- (age 20), mid- (age 50) and late-life (age ≥ 55, mean age 60.7 years) and weight change with incident BPH-related outcomes (including self-reported nocturia and physician diagnosis of BPH, digital rectal examination-estimated prostate volume ≥ 30 cc, and prostate-specific antigen [PSA] concentration > 1.4 ng/mL) were examined using Poisson regression with robust variance estimation. Results Men who were obese in late-life were 25% more likely to report nocturia (Relative Risk (RR): 1.25, 95% Confidence Interval (CI): 1.11–1.40; p-trendfor continuous BMI < 0.0001) and men who were either overweight or obese in late-life were more likely to report a prostate volume ≥ 30 cc (RRoverweight: 1.13, 95% CI 1.07–1.21; RRobese: 1.10, 95% CI 1.02–1.19; p-trendfor continuous BMI = 0.017) as compared to normal weight men. Obesity at ages 20 and 50 was similarly associated with both nocturia and prostate volume ≥ 30 cc. Considering trajectories of body size, men who were normal weight at age 20 and became overweight or obese by later-life had increased risks of nocturia (RRnormal to overweight: 1.09, 95% CI 0.98–1.22; RRnormal to obese: 1.28, 95% CI 1.10–1.47) and a prostate volume ≥ 30 cc (RRnormal to overweight: 1.12, 95% CI 1.05–1.20). Too few men were obese early in life to examine the independent effect of early-life body size. Later-life body size modified the association between physical activity and nocturia. Conclusions We found that later-life body size, independent of early-life body size, was associated with adverse BPH outcomes, suggesting that interventions to reduce body size even late in life can potentially reduce the burden of BPH-related outcomes and nocturia.

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