Comparison of gene expression profiles in the blood, hippocampus and prefrontal cortex of rats

Recent evidence from our laboratory documents functional resilience to retinal ischemic injury in untreated mice derived from parents exposed to repetitive hypoxic conditioning (RHC) before breeding. To begin to understand the epigenetic basis of this intergenerational protection, we used methylated DNA immunoprecipitation and sequencing to identify genes with differentially methylated promoters (DMGPs) in the prefrontal cortex of mice treated directly with the same RHC stimulus (F0-RHC) and in the prefrontal cortex of their untreated F1-generation offspring (F1-*RHC). Subsequent bioinformatic analyses provided key mechanistic insights into how changes in gene expression secondary to promoter hypo- and hypermethylation might afford such protection within and across generations. We found extensive changes in DNA methylation in both generations consistent with the expression of many survival-promoting genes, with twice the number of DMGPs in the cortex of F1*RHC mice relative to their F0 parents that were directly exposed to RHC. In contrast to our hypothesis that similar epigenetic modifications would be realized in the cortices of both F0-RHC and F1-*RHC mice, we instead found relatively few DMGPs common to both generations; in fact, each generation manifested expected injury resilience via distinctly unique gene expression profiles. Whereas in the cortex of F0-RHC mice, predicted protein-protein interactions reflected activation of an anti-ischemic phenotype, networks activated in F1-*RHC cortex comprised networks indicative of a much broader cytoprotective phenotype. Altogether, our results suggest that the intergenerational transfer of an acquired phenotype to offspring does not necessarily require the faithful recapitulation of the conditioning-modified DNA methylome of the parent.

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Gene Expression Profiles in Parkinson Disease Prefrontal Cortex Implicate FOXO1 and Genes under Its Transcriptional Regulation

PLoS Genetics ◽

10.1371/journal.pgen.1002794 ◽

2012 ◽

Vol 8 (6) ◽

pp. e1002794 ◽

Cited By ~ 44

Author(s):

Alexandra Dumitriu ◽

Jeanne C. Latourelle ◽

Tiffany C. Hadzi ◽

Nathan Pankratz ◽

Dan Garza ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Prefrontal Cortex ◽

Parkinson Disease ◽

Expression Profiles ◽

Gene Expression Profiles

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Gene expression profiles in the prefrontal cortex of SHR rats by cDNA microarrays

Molecular Biology Reports ◽

10.1007/s11033-009-9596-1 ◽

2009 ◽

Vol 37 (4) ◽

pp. 1733-1740 ◽

Cited By ~ 14

Author(s):

Jie Qiu ◽

Qin Hong ◽

Rong-hua Chen ◽

Mei-ling Tong ◽

Min Zhang ◽

...

Keyword(s):

Gene Expression ◽

Prefrontal Cortex ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Cdna Microarrays ◽

Shr Rats

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Effect of Electroconvulsive Shock and Magnetic Seizure on Gene Expression Profiles in the Prefrontal Cortex of the Rhesus Monkey

Journal of Ect ◽

10.1097/01.yct.0000264356.75257.80 ◽

2007 ◽

Vol 23 (1) ◽

pp. 53

Author(s):

Loubna Erraji-Benchekroun ◽

Sarah H. Lisanby ◽

Victoria Arango ◽

Hanga Galfalvy ◽

Paul Pavlidis ◽

...

Keyword(s):

Gene Expression ◽

Prefrontal Cortex ◽

Rhesus Monkey ◽

Electroconvulsive Shock ◽

Expression Profiles ◽

Gene Expression Profiles

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Gene expression profiles underlying aggressive behavior in the prefrontal cortex of cattle

BMC Genomics ◽

10.1186/s12864-021-07505-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Paulina G. Eusebi ◽

Natalia Sevane ◽

Thomas O’Rourke ◽

Manuel Pizarro ◽

Cedric Boeckx ◽

...

Keyword(s):

Gene Expression ◽

Prefrontal Cortex ◽

Aggressive Behavior ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Mental States ◽

Mapk Signaling ◽

Molecular Architecture ◽

Functional Interpretation ◽

High Heritability

Abstract Background Aggressive behavior is an ancient and conserved trait, habitual for most animals in order to eat, protect themselves, compete for mating and defend their territories. Genetic factors have been shown to play an important role in the development of aggression both in animals and humans, displaying moderate to high heritability estimates. Although such types of behaviors have been studied in different animal models, the molecular architecture of aggressiveness remains poorly understood. This study compared gene expression profiles of 16 prefrontal cortex (PFC) samples from aggressive and non-aggressive cattle breeds: Lidia, selected for agonistic responses, and Wagyu, selected for tameness. Results A total of 918 up-regulated and 278 down-regulated differentially expressed genes (DEG) were identified, representing above-chance overlap with genes previously identified in studies of aggression across species, as well as those implicated in recent human evolution. The functional interpretation of the up-regulated genes in the aggressive cohort revealed enrichment of pathways such as Alzheimer disease-presenilin, integrins and the ERK/MAPK signaling cascade, all implicated in the development of abnormal aggressive behaviors and neurophysiological disorders. Moreover, gonadotropins, are up-regulated as natural mechanisms enhancing aggression. Concomitantly, heterotrimeric G-protein pathways, associated with low reactivity mental states, and the GAD2 gene, a repressor of agonistic reactions associated with PFC activity, are down-regulated, promoting the development of the aggressive responses selected for in Lidia cattle. We also identified six upstream regulators, whose functional activity fits with the etiology of abnormal behavioral responses associated with aggression. Conclusions These transcriptional correlates of aggression, resulting, at least in part, from controlled artificial selection, can provide valuable insights into the complex architecture that underlies naturally developed agonistic behaviors. This analysis constitutes a first important step towards the identification of the genes and metabolic pathways that promote aggression in cattle and, providing a novel model species to disentangle the mechanisms underlying variability in aggressive behavior.

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Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2 diabetic rats

BMC Genomics ◽

10.1186/1471-2164-13-81 ◽

2012 ◽

Vol 13 (1) ◽

pp. 81 ◽

Cited By ~ 33

Author(s):

Omar Abdul-Rahman ◽

Maria Sasvari-Szekely ◽

Agota Ver ◽

Klara Rosta ◽

Bernadett K Szasz ◽

...

Keyword(s):

Gene Expression ◽

Prefrontal Cortex ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Diabetic Rats ◽

Altered Gene Expression ◽

Altered Gene ◽

Type 2 Diabetic

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Gene expression profiles underlying aggressive behavior in the prefrontal cortex of cattle

10.1101/2020.07.09.194704 ◽

2020 ◽

Author(s):

Paulina G. Eusebi ◽

Natalia Sevane ◽

Manuel Pizarro ◽

Marta Valero ◽

Susana Dunner

Keyword(s):

Gene Expression ◽

Prefrontal Cortex ◽

Aggressive Behavior ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Mental States ◽

Mapk Signaling ◽

Meat Production ◽

Molecular Architecture ◽

Functional Interpretation

SummaryAggressive behavior is an ancient and conserved trait considered habitual and essential for most animals in order to eat, protect themselves from predators and also to compete for mating and defend their territories. Genetic factors have shown to play an important role in the development of aggression both in animals and humans, displaying moderate to high heritability estimates. However, although such types of conducts have been studied in different animal models, the molecular architecture of aggressiveness remains poorly understood. This study compared gene expression profiles of 16 prefrontal cortex (PFC) samples from aggressive and non-aggressive cattle breeds: Lidia, selected for agonistic responses, and Wagyu, specialized on meat production and selected for tameness. RNA sequencing was used to identify 918 up and 278 down-regulated differentiated expressed genes (DEG). The functional interpretation of the up-regulated genes in the aggressive cohort revealed enrichment of pathways such as the Alzheimer disease-presenilin, integrins or the ERK/MAPK signaling cascade, all implicated in the development of abnormal aggressive behaviors and neurophysiological disorders. Moreover, gonadotropins, leading to testosterone release, are also up-regulated as natural mechanisms enhancing aggression. Concomitantly, heterotrimeric G-protein pathways, associated with low reactivity mental states, and the GAD2 gene, a repressor of agonistic reactions at PFC, are down-regulated, guaranteeing the development of the adequate responses required by the aggressive Lidia cattle. We also identified six upstream regulators, whose functional activity fits with the etiology of abnormal behavioral responses associated with aggression. These results provide valuable insights into the complex architecture that underlie naturally developed agonistic behaviors.

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Gene Expression Profiles Underlying Aggressive Behavior in the Prefrontal Cortex of Cattle

10.21203/rs.3.rs-146648/v1 ◽

2021 ◽

Author(s):

Paulina G. Eusebi ◽

Natalia Sevane ◽

Thomas O´Rourke ◽

Manuel Pizarro ◽

Cedric Boeckx ◽

...

Keyword(s):

Gene Expression ◽

Prefrontal Cortex ◽

Aggressive Behavior ◽

Expression Profiles ◽

Model Organism ◽

Gene Expression Profiles ◽

Mental States ◽

Mapk Signaling ◽

Molecular Architecture ◽

Functional Interpretation

Abstract Background: Aggressive behavior is an ancient and conserved trait habitual for most animals in order to eat, protect themselves, compete for mating and defend their territories. Genetic factors have been shown to play an important role in the development of aggression both in animals and humans, displaying moderate to high heritability estimates. Although, such types of conducts have been studied in different animal models, the molecular architecture of aggressiveness remains poorly understood. This study compared gene expression profiles of 16 prefrontal cortex (PFC) samples from aggressive and non-aggressive cattle breeds: Lidia, selected for agonistic responses, and Wagyu, selected for tameness. Results: A total of 918 up-regulated and 278 down-regulated DEG were identified. The functional interpretation of the up-regulated genes in the aggressive cohort revealed enrichment of pathways such as the Alzheimer disease-presenilin, integrins or the ERK/MAPK signaling cascade, all implicated in the development of abnormal aggressive behaviors and neurophysiological disorders. Moreover, gonadotropins, are also up-regulated as natural mechanisms enhancing aggression. Concomitantly, heterotrimeric G-protein pathways, associated with low reactivity mental states, and the GAD2 gene, a repressor of agonistic reactions associated with PFC activity, are down-regulated, promoting the development of the aggressive responses selected for in Lidia cattle. We also identified six upstream regulators, whose functional activity fits with the etiology of abnormal behavioral responses associated with aggression. Conclusions: These transcriptional correlates of aggression, resulting, at least in part, from controlled artificial selection, can provide valuable insights into the complex architecture that underlies naturally developed agonistic behaviors.This analysis constitutes a first important step towards the identification of the genes and metabolic pathways that impulse aggression in cattle and, hence, we are providing a novel species as model organism for disentangling the mechanisms underlying variability in aggressive behavior.

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