Project description:We show that infant trauma, as modeled by infant paired odor-shock conditioning, results in later life depressive-like behavior that can be modulated by learned infant cues (i.e., odor previously paired with shock). We have previously shown that this infant attachment odor learning paradigm results in the creation of a new artificial maternal odor that is able to control pup behavior and retain its value throughout development. Here, we assess the mechanism by which this artificial maternal odor is able to rescue depressive-like behavior and show that this anti-depressant like effect results in glucocorticoid and serotonin (5-HT) related changes in amygdala gene expression and is dependent on amygdala 5-HT. Furthermore, increasing amygdala 5-HT and blocking corticosterone (CORT) in the absence of odor mimics the adult rescue effects elicited by the artificial maternal odor, suggesting a mechanism by which odor presentation exerts its repair effects. There are three experimental groups: 1: pups with no infant shock and the adult forced swim test (FST)with no odor; 2. pups with infant odor-shock pairing and the adult forced swim test (FST) with no odor; 3. pups with infant odor-shock pairing and adult forced swim test with infant odor.
Project description:We show that infant trauma, as modeled by infant paired odor-shock conditioning, results in later life depressive-like behavior that can be modulated by learned infant cues (i.e., odor previously paired with shock). We have previously shown that this infant attachment odor learning paradigm results in the creation of a new artificial maternal odor that is able to control pup behavior and retain its value throughout development. Here, we assess the mechanism by which this artificial maternal odor is able to rescue depressive-like behavior and show that this anti-depressant like effect results in glucocorticoid and serotonin (5-HT) related changes in amygdala gene expression and is dependent on amygdala 5-HT. Furthermore, increasing amygdala 5-HT and blocking corticosterone (CORT) in the absence of odor mimics the adult rescue effects elicited by the artificial maternal odor, suggesting a mechanism by which odor presentation exerts its repair effects.
Project description:Analysis of T3 and CORT dependent gene expression tested in the mouse hippocampal neuronal cell line HT-22. The experiment was done to identify genes which are differentially regulated by the two hormones as well as to identify genes which are synergistically regulated by combined T3 + CORT treatment. Results provide an exploratory dataset for studying T3 and CORT regulation in mouse hippocampal neurons.
Project description:Behavioral transitions Young infant rats paradoxically prefer odors paired with shock but older pups learn aversions. This transition is amygdala- and corticosterone-dependent. Microarray results showed downregulated dopaminergic presynaptic function in the amygdala with preference learning. Corticosterone injected 8-day-old pups and untreated 12-day-old pups learn aversions and had dopaminergic upregulation in the amygdala.
Project description:Neonatal molecular biomarkers of neurobehavioral responses (measures of brain-behavior relationships), when combined with neurobehavioral performance measures, could lead to better predictions of long-term developmental outcomes. To this end, we examined whether variability in epigenomic measures from buccal cells were associated with neurobehavioral profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA) and participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study (N=536). We tested whether epigenetic age, age acceleration, or DNA methylation (DNAm) levels at individual loci, measured via the Illumina EPIC microarray, differed between infants based on their NICU Network Neurobehavioral Scale (NNNS) profile classifications, ranging from most optimal to atypical. We adjusted for recruitment site, infant sex, PMA, and tissue heterogeneity. Infants with an optimally well-regulated NNNS profile had older epigenetic age compared to other NOVI infants (β1 = 0.201, p-value = 0.026), but no significant difference in age acceleration. In contrast, infants with an atypical NNNS profile had differential methylation at 29 CpG sites (FDR < 10%). Some of the genes annotated to these CpGs included PLA2G4E, TRIM9, GRIK3, and MACROD2, which have previously been associated with neurological structure and function, or with neurobehavioral disorders. These findings contribute to the existing evidence that neonatal epigenetic variations in buccal cells may be informative for infant neurobehavior.
Project description:Behavioral transitions Young infant rats paradoxically prefer odors paired with shock but older pups learn aversions. This transition is amygdala- and corticosterone-dependent. Microarray results showed downregulated dopaminergic presynaptic function in the amygdala with preference learning. Corticosterone injected 8-day-old pups and untreated 12-day-old pups learn aversions and had dopaminergic upregulation in the amygdala. 8 day saline or corticosterone treated- or 12 day old untreated rat pups were trained with odor-shock pairings. Immediately after training pups were sacrificed and the amygdala dissected out. Controls were unpaired shock-odor groups.Paired and unpaired groups were processed together for each experimental condition. Paired and unpaired data were compared by ranked products.
Project description:Pain experienced within a social context impacts infant neurobehavioral responses and initiates an altered developmental trajectory of pain and affect processing that diverges from experiencing pain alone. We used microarrays to detail the gene expression following pain with and without the mother at different preweaning ages
Project description:We report changes in GR and Pol II binding profiles genome-wide upon treatment with corticosterone (Cort) for 20 minutes, treatment with Cort for 20 minutes followed by hormone withdrawal for 40 minutes, 60 minutes continuous stimulation with Cort, and 60 minutes continuous stimulation with Dexamethasone (Dex). We examine GR binding upon following treatments: 0' Cort, 20' Cort, 60' Cort Pulsed, 60' Cort Constant; Pol II binding upon following treatments: 0' Cort, 20' Cort, 60' Cort Pulsed, 60' Cort Constant, 60' Dex Constant; Pol II binding upon Mock treatments simulating 0' Cort, 20' Cort, 60' Cort Pulsed, 60' Cort Constant; CTCF binding profile of untreated cells.
Project description:Electroacupuncture (EA) has long been used to treat surgery-induced hypothalamic-pituitary-adrenal (HPA) axis dysfunction. However, its target gene expression profiles in the brain remain unclear. Thus, the aim of the present study was to clarify the potential targets of EA based on RNA sequencing techniques (RNA-seq). Rats were randomly divided into normal control, hepatectomy surgery (HT), HT+EA, and HT+sham EA groups followed by RNA-seq of two representative nuclei in the hypothalamus and amygdala.