Biology subjects

Sharafeddin, F.

Publications and source records attributed to Sharafeddin, F..

3 recordsLinked to original sources

bioRxiv2024

Shifts in Naturalistic Behaviors Induced by Early Social Isolation Stress are Associated with Adult Binge-like Eating in Female Rats

Binge eating (BE) is a highly pervasive maladaptive coping strategy in response to severe early life stress such as emotional and social neglect. BE is described as repeated episodes of uncontrolled eating and is tightly linked with comorbid mental health concerns. Despite social stressors occurring at a young age, the onset of BE typically does not occur until adulthood providing an interval for potential therapeutic intervention. Currently, our knowledge of longitudinal noninvasive digital biomarkers predictive of BE needs further development. Monitoring longitudinal impacts of adolescent social isolation stress on naturalistic behaviors in rats will enable the identification of noninvasive digital markers of disease progression to predict adult eating strategies. Recognizing adolescent naturalistic behaviors shaped by social stress informs our understanding of the underlying neurocircuits most effected. This study aimed to monitor and identify longitudinal behavioral shifts to enhance predictive capabilities in a rat model of social isolation stress-induced BE. We placed Paired (n=12) and Socially Isolated (SI, n=12) female rats in observational home cages weekly for seven weeks to evaluate the effect of SI on 10 naturalistic behaviors. All 10 naturalistic behaviors were simultaneously detected and tracked using Noldus Ethovision XT automated recognition software. Composite phenotypic z-scores were calculated by standardizing all 10 behaviors. When transitioning into adulthood, all rats underwent conventional emotionality testing and were exposed to a Western-like high fat diet (WD, 43% kcal from fat) to evaluate BE. Longitudinal assessments revealed SI-induced shifts in adolescent phenotypic z-scores and that sniffing, unsupported rearing, jumping, and twitching were the most susceptible to SI. SI increased emotionality compared to the Paired controls. Finally, we identified adolescent twitching as a digital biomarker of adult WD consumption. This study employed novel approaches to identify early life predictive biomarkers of adult eating strategies and laid a foundation for future investigations.

neuroscience↗

bioRxiv2023

Early-life obesogenic environment integrates immunometabolic and epigenetic signatures governing neuroinflammation

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/537874v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1bb1277org.highwire.dtl.DTLVardef@b978dborg.highwire.dtl.DTLVardef@adafc8org.highwire.dtl.DTLVardef@efa0f3_HPS_FORMAT_FIGEXP M_FIG Early life trauma and obesogenic diet effects of feeding control.Consumption of a Western-like high-saturated fat diet (WD, 42% kcal from fat) during adolescence in combination with (2) Exposure to early-life psychosocial stress leads to (3) changes in brain neurocircuitry and metabolic dysregulation. These alterations lead to (4) stress susceptibility, (5) emotional and feeding dysregulation, and (6) obesity. Dysregulation of feeding control and obesity leads to increased hedonic feeding and engages individuals in a cycle of aberrant feeding behaviors. C_FIG BackgroundChildhood overweight/obesity is associated with the development of stress-related psychopathology. However, the pathways connecting childhood obesity to stress susceptibility remain poorly understood. Here, we used a systems biology approach to determine linkages underlying obesity-induced stress susceptibility. MethodsSixty-two (62) adolescent Lewis rats (PND21) were fed for four weeks with a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a matched control diet (CD, 13% kcal from fat). Subsequently, a group of rats (n = 32) was exposed to a well-established 31-day model of predator exposures and social instability (PSS). The effects of the WD and PSS were assessed with a comprehensive battery of behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), high throughput 16S ribosomal RNA gene sequencing for gut microbiome profiling, hippocampal microglia morphological and gene analysis, and gene methylation status of the stress marker, FKBP5. Parallel experiments were performed on human microglial cells (HMC3) to examine molecular mechanisms by which palmitic acid primes these cells to aberrant responses to cortisol. ResultsRats exposed to the WD and PSS exhibited deficits in sociability indices and increased fear and anxiety-like behaviors, food consumption, and body weight. WD and PSS interacted to alter indices of microstructural integrity within the hippocampal formation (subiculum) and subfields (CA1). Microbiome diversity and taxa distribution revealed that WD/PSS exposure caused significant shifts in the diversity of gut dominant bacteria and decreased the abundance of various members of the Firmicutes phylum, including Lachnospiracae NK4A136. Interestingly, the WD and PSS synergized to promote hippocampal microglia morphological and gene signatures implicated in neuroinflammation. These alterations were associated with changes in the microbiome, and in the expression and methylation status of the corticosterone receptor chaperone rat gene Fkbp5. HMC3 responses to cortisol were markedly disrupted after incubating cells in palmitate, shown by morphological changes and pro-inflammatory cytokine expression and release. Notably, these effects were partly mediated by the human FKBP5 gene. ConclusionsThe combination of psychosocial stress and poor diet during adolescence has a deleterious synergistic impact on brain health. This study enhances our understanding of mechanisms and adaptations by which obesogenic environments shape the maturational trajectories of common neurobiological correlates of resilience. HighlightsO_LIObesogenic diet consumption during adolescence leads to stress-induced anxiety-like behaviors in rats. C_LIO_LIExposure to an obesogenic environment during adolescence alters indices of hippocampal microstructural integrity. C_LIO_LIObesogenic diet and chronic stress promote selective gut microbiota dysbiosis. C_LIO_LIObesogenic diet and chronic stress synergize to expand putative pro-inflammatory microglia populations in the CA1 subfield of the hippocampus. C_LIO_LIObesogenic diet and chronic stress influence hippocampal Fkbp5 gene methylation status at specific sites. C_LIO_LIFKBP5 integrates microglial pro-inflammatory signals under obesogenic conditions. C_LI

neuroscience↗

bioRxiv2023

Prefrontal cortical protease TACE/ADAM17 is involved in neuroinflammation and stress-related eating alterations

Childhood traumatic stress profoundly affects prefrontal cortical networks regulating top-down control of eating and body weight. However, the neurobiological mechanisms contributing to trauma-induced aberrant eating behaviors remain largely unknown. Traumatic stress influences brain immune responses, which may, in turn, disrupt prefrontal cortical networks and behaviors. The tumor necrosis factor alpha-converting enzyme / a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and neuroinflammation. This study aimed to determine the role of TACE/ADAM17 on traumatic stress-induced disruption of eating patterns. We demonstrate a novel mechanistic connection between prefrontal cortical TACE/ADAM17 and trauma-induced eating behaviors. Fifty-two (52) adolescent Lewis rats (postnatal day, PND, 15) were injected intracerebrally either with a novel Accell SMARTpool ADAM17 siRNA or a corresponding siRNA vehicle. The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Observation cages were used to monitor ethological behaviors in a more naturalistic environment over long periods. We found that traumatic stress blunts startle reactivity and alter eating behaviors (increased intake and disrupted eating patterns). We also found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited decreased eating and increased grooming behaviors compared to controls. These changes were associated with decreased AIF-1 expression (a typical marker of microglia and neuroinflammation). This study demonstrates that prefrontal cortical TACE/ADAM17 is involved in neuroinflammation and may play essential roles in regulating feeding patterns under stress conditions. TACE/ADAM17 represents a promising target to ameliorate inflammation-induced brain and behavior alterations.

neuroscience↗