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Ferret Odor Induces Novel Gene Pathways in the Ventromedial Hypothalamus
Nearly 40% of Americans are obese and this can be countered by increasing calories burned. Muscle thermogenesis is a possible untapped source for increasing energy expenditure. Elevating thermogenesis increases energy expenditure and is linked to weight loss. Our research program has shown that exposing rats to predator odor (PO) induces a rapid and robust increase in muscle thermogenesis that peaks by 30 min and settles to near baseline after 4 hours. We hypothesize that this is mediated in the brain by the ventromedial hypothalamus (VMH) because of the importance of the VMH in regulating body weight, muscle metabolism, sympathetic nervous system activity, and the behavioral response to predator threat. We investigated possible PO-induced changes in the VMH by exposing rats to predator odor for 30 minutes to 4 hours. Tissue samples were taken from the VMH, and mRNA expression was measured using qPCR, showing an increase in Sirt 1 and Bdnf, but not SF1, after 4 hours of PO exposure. RNA-sequencing analyses identified 164 differentially expressed genes (DEGs), 65 enriched gene ontology terms, and 28 genome pathways revealing themes of immune response, oxidative stress, and synaptic plasticity. This allowed us to conclude that PO exposure causes upregulation of novel genes pathways. - Image
Effects of Early Life Neglect on Adolescent Cocaine Use and Expression of Fibroblast Growth Factor-2 in the Brain
Early-life adversity (ELA) increases the risk for development of psychopathologies in adolescence and adulthood. Childhood neglect is a potent form of ELA and can be modeled through neonatal maternal separation. Maternal separation has been shown to alter cognition, learning and memory later in life. Here, we examined the contribution of maternal separation to the development of substance use disorder in adolescence, and whether changes in regional protein expression in the brain persist into adulthood. First, male and female rats exposed to maternal separation were compared to controls for changes in localized expression of the developmental growth factor, fibroblast growth factor-2 (FGF2), in several brain regions using immunohistochemistry. FGF2 is known to be upregulated by cocaine experience, is protective against fear over-expression and is a candidate biomarker for vulnerability and resilience to development of comorbid psychopathologies. Next, we examined whether maternal separation impacted sensitivity in adolescence to cocaine using the conditioned place preference paradigm, in which one of two chambers is associated with cocaine. Finally, we determined whether maternal separation altered regional FGF2 expression in the brain during adulthood, and if cocaine experience in adolescence had an impact. We are currently processing the brain tissue to examine regional FGF2 expression and have completed the conditioned place preference protocol. Our results will determine whether FGF2 is a potential risk or resilience factor for the development of psychopathologies and will pave the way for future studies examining comorbid addiction and fear disorders. Mitochondrial Dynamics in Neurodegenerative Mouse Models
Neurodegenerative diseases are becoming more common in today’s world. Two of the more prominent diseases that fall into this category are multiple sclerosis (MS) and Alzheimer’s disease (AD). A hallmark for both of these diseases is mitochondrial dysfunction. Mitochondrial dysfunction causes an increase in the number of damaged mitochondria, which is linked to a decrease in the energy supply for the cell. Mitophagy is a mechanism known for eliminating damaged mitochondria and is impaired in neurodegenerative diseases. This causes an accumulation of damaged mitochondria in the cell leading to loss of function. We have also shown that a dietary factor known as betaine, is able to restore energy production within the dysfunctional mitochondria. In the present study, we are investigating the role of betaine in both AD and cuprizone mouse models, hypothesizing that betaine will restore energy production by eliminating damaged mitochondria using mitophagy.- Image
The Role of the Locus Coeruleus on Regulating Sickness-like Behaviors
Elevated peripheral cytokines result in sickness and depression-like behaviors by signaling through the vagus nerve. Stimulation of the vagus nerve activates noradrenergic neurons in the nucleus of the solitary tract (NTS) and release of norepinephrine (NE) at projection sites that regulate behavior. Previous studies indicate that neurons in the locus coeruleus (LC) inhibit neurons in the NTS. This led to the hypothesis that LC neurons may act as a brake to inhibit sickness behaviors. To test this hypothesis, rats underwent baseline behavioral testing before being injected with either saline or DSP4, a neurotoxin that lesions LC neurons. Three weeks later animals underwent further behavioral testing before all animals received live E.coli injections and sickness behaviors were recorded. We expected lesioning the LC would result in greater sickness behaviors following E.coli by removing the inhibitory regulation of NTS projection neurons; however, lesioned animals had similar body weights, food intake, and sucrose intake compared to controls following E.coli challenge. Interestingly, DSP4 treated rats showed greater anxiety-like behaviors in an open field test three weeks following DPS4 and less sickness behaviors in an open field following E.coli compared to controls. The results did not support our initial hypothesis, but do support a role for LC neurons in regulating sickness and/or depression/anxiety-like behaviors. Future studies will look more into the role the LC plays in regulating behaviors and the interactions between NTS, LC, and prefrontal cortex (an area important for emotional and motivated behaviors).