scholarly journals Too much, too young? Altered corticolimbic axonal innervation and resting state functional connectivity suggests sex-dependent outcomes in a rat model of early life adversity

2019 ◽  
Author(s):  
Jennifer A. Honeycutt ◽  
Camila Demaestri ◽  
Shayna Peterzell ◽  
Marisa M. Silveri ◽  
Xuezhu Cai ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Life Stress ◽  
Early Life ◽  
Female Rats ◽  
Brain Maturation ◽  
Resting State Functional Connectivity ◽  
Early Maturation ◽  
Male And Female Rats ◽  
Increased Risk

AbstractAdverse early experiences significantly alter behavioral and neural trajectories via aberrant brain maturation. Children with a history of early life stress (ELS) exhibit maladaptive behaviors and increased risk of mental illness later in life. Evidence in ELS-exposed humans identifies a role of atypical corticolimbic development; specifically, within amygdala-prefrontal cortex (PFC) circuits, and show precocially mature task-based corticolimbic functional connectivity (FC). However, the neurobiological substrates of such ELS-driven developmental changes remain unknown. Here, we identify putative neurobiological changes to determine the timeline of developmental perturbations following ELS in rats. Anterograde axonal tracing from basolateral amygdala (BLA) to pre- and infralimbic (PL, IL) PFC was quantified at postnatal days (PD)28, 38, and 48, along with anxiety-like behavior, in maternally separated (ELS) or control reared (CON) male and female rats. Resting state (rs)FC was assessed at PD28 and PD48 in a separate cohort. We report that ELS-exposed female rats show early maturation of BLA-PFC innervation at PD28, with ELS-related changes in males not appearing until PD38. ELS disrupted the maturation of rsFC from PD28 to PD48 in females, with enduring relationships between early rsFC and later anxiety-like behavior. Only transient ELS-related changes in rsFC were seen in male PL. Together, these data provide evidence that female rats may be more vulnerable to the effects of ELS via precocial BLA-PFC innervation, which may drive altered corticolimbic rsFC. These data also provide evidence that increased BLA-IL rsFC is associated with behavioral resiliency following ELS in female rats, providing mechanistic insight into the underlying etiology of adversity-induced vulnerability and resiliency.

scholarly journals Regional homogeneity and resting state functional connectivity: Associations with exposure to early life stress

2013 ◽  
Vol 214 (3) ◽  
pp. 247-253 ◽  
Author(s):  
Noah S. Philip ◽  
Yuliya I. Kuras ◽  
Thomas R. Valentine ◽  
Lawrence H. Sweet ◽  
Audrey R. Tyrka ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Regional Homogeneity ◽  
Resting State Functional Connectivity

scholarly journals Early-Life Stress Modulates Gut Microbiota and Peripheral and Central Inflammation in a Sex-Dependent Manner

2021 ◽  
Vol 22 (4) ◽  
pp. 1899 ◽  
Author(s):  
Hae Jeong Park ◽  
Sang A. Kim ◽  
Won Sub Kang ◽  
Jong Woo Kim
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Male And Female Rats

Recent studies have reported that changes in gut microbiota composition could induce neuropsychiatric problems. In this study, we investigated alterations in gut microbiota induced by early-life stress (ELS) in rats subjected to maternal separation (MS; 6 h a day, postnatal days (PNDs) 1–21), along with changes in inflammatory cytokines and tryptophan-kynurenine (TRP-KYN) metabolism, and assessed the differences between sexes. High-throughput sequencing of the bacterial 16S rRNA gene showed that the relative abundance of the Bacteroides genus was increased and that of the Lachnospiraceae family was decreased in the feces of MS rats of both sexes (PND 56). By comparison, MS increased the relative abundance of the Streptococcus genus and decreased that of the Staphylococcus genus only in males, whereas the abundance of the Sporobacter genus was enhanced and that of the Mucispirillum genus was reduced by MS only in females. In addition, the levels of proinflammatory cytokines were increased in the colons (IFN-γ and IL-6) and sera (IL-1β) of the male MS rats, together with the elevation of the KYN/TRP ratio in the sera, but not in females. In the hippocampus, MS elevated the level of IL-1β and the KYN/TRP ratio in both male and female rats. These results indicate that MS induces peripheral and central inflammation and TRP-KYN metabolism in a sex-dependent manner, together with sex-specific changes in gut microbes.

scholarly journals The Interaction of Child Abuse and rs1360780 of the FKBP5 Gene is Associated with Amygdala Resting-State Functional Connectivity in Young Adults

2020 ◽  
Author(s):  
Christiane Wesarg ◽  
Ilya M. Veer ◽  
Nicole Y. L. Oei ◽  
Laura S. Daedelow ◽  
Tristram A. Lett ◽  
...  
Keyword(s):  
Child Abuse ◽  
Functional Connectivity ◽  
Resting State ◽  
Life Stress ◽  
Salience Network ◽  
Resting State Functional Connectivity ◽  
Brain Areas ◽  
Functional Changes ◽  
Intermediate Phenotypes ◽  
History Of

AbstractExtensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p < .025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase risk for psychopathology.

scholarly journals Differential Alterations in Resting State Functional Connectivity Associated with Depressive Symptoms and Early Life Adversity

2021 ◽  
Vol 11 (5) ◽  
pp. 591
Author(s):  
Eleonora Fadel ◽  
Heinz Boeker ◽  
Matti Gaertner ◽  
Andre Richter ◽  
Birgit Kleim ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Functional Connectivity ◽  
Childhood Abuse ◽  
Resting State ◽  
Early Life ◽  
Clinical Symptoms ◽  
Future Research ◽  
Resting State Functional Connectivity ◽  
Early Life Adversity ◽  
Depression Subtypes

Depression and early life adversity (ELA) are associated with aberrant resting state functional connectivity (FC) of the default mode (DMN), salience (SN), and central executive networks (CEN). However, the specific and differential associations of depression and ELA with FC of these networks remain unclear. Applying a dimensional approach, here we analyzed associations of FC between major nodes of the DMN, SN, and CEN with severity of depressive symptoms and ELA defined as childhood abuse and neglect in a sample of 83 healthy and depressed subjects. Depressive symptoms were linked to increased FC within the SN and decreased FC of the SN with the DMN and CEN. Childhood abuse was associated with increased FC within the SN, whereas childhood neglect was associated with decreased FC within the SN and increased FC between the SN and the DMN. Our study thus provides evidence for differential associations of depressive symptoms and ELA with resting state FC and contributes to a clarification of previously contradictory findings. Specific FC abnormalities may underlie specific cognitive and emotional impairments. Future research should link specific clinical symptoms resulting from ELA to FC patterns thereby characterizing depression subtypes with specific neurobiological signatures.

scholarly journals Altered corticolimbic connectivity reveals sex-specific adolescent outcomes in a rat model of early life adversity

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jennifer A Honeycutt ◽  
Camila Demaestri ◽  
Shayna Peterzell ◽  
Marisa M Silveri ◽  
Xuezhu Cai ◽  
...  
Keyword(s):  
Early Life ◽  
Basolateral Amygdala ◽  
Maternal Separation ◽  
Female Rats ◽  
Resting State Functional Connectivity ◽  
Early Life Adversity ◽  
Adolescent Outcomes ◽  
Male And Female Rats ◽  
Neurobiological Substrates ◽  
Separate Cohort

Exposure to early-life adversity (ELA) increases the risk for psychopathologies associated with amygdala-prefrontal cortex (PFC) circuits. While sex differences in vulnerability have been identified with a clear need for individualized intervention strategies, the neurobiological substrates of ELA-attributable differences remain unknown due to a paucity of translational investigations taking both development and sex into account. Male and female rats exposed to maternal separation ELA were analyzed with anterograde tracing from basolateral amygdala (BLA) to PFC to identify sex-specific innervation trajectories through juvenility (PD28) and adolescence (PD38;PD48). Resting-state functional connectivity (rsFC) was assessed longitudinally (PD28;PD48) in a separate cohort. All measures were related to anxiety-like behavior. ELA-exposed rats showed precocial maturation of BLA-PFC innervation, with females affected earlier than males. ELA also disrupted maturation of female rsFC, with enduring relationships between rsFC and anxiety-like behavior. This study is the first providing both anatomical and functional evidence for sex- and experience-dependent corticolimbic development.

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