Neuroinflammation at the interface of depression and cardiovascular disease: Evidence from rodent models of social stress

A large body of evidence has emerged linking stressful experiences, particularly from one's social environment, with psychiatric disorders. However, vast individual differences emerge in susceptibility to developing stress-related pathology which may be due to distinct differences in the inflammatory response to social stress. Furthermore, depression is an independent risk factor for cardiovascular disease, another inflammatory-related disease, and results in increased mortality in depressed patients. This review is focused on discussing evidence for stress exposure resulting in persistent or sensitized inflammation in one individual while this response is lacking in others. Particular focus will be directed towards reviewing the literature underlying the impact that neuroinflammation has on neurotransmitters and neuropeptides that could be involved in the pathogenesis of comorbid depression and cardiovascular disease. Finally, the theme throughout the review will be to explore the notion that stress-induced inflammation is a key player in the high rate of comorbidity between psychosocial disorders and cardiovascular disease

Asymmetric Synthetic Strategy of Fosfomycin Using Biocatalysis

This presentation was given at Pacifichem

Synthesis of Fosfomycin Using Whole-Cell Biocatalysis as the Key Step

This presentation was given at the Armstrong Student Scholarship Symposium

Synthesis of Fosfomycin Using Whole-Cell Biocatalysis as the Key Step

This presentation was given at the ACS National Meeting

Asymmetric Synthesis of (-)-fosfomycin and its Trans- (1S,2S)-diastereomer Using a Biocatalytic Reduction as the Key Step

Fosfomycin is a gram positive and gram negative antibiotic that contains an asymmetric epoxide. An enzyme library was screened for its ability to reduce dimethyl(1-chloro-2-oxopropyl)phosphonate to the corresponding asymmetric chlorohydrin. Homology models were built in MOE, which were shown to accurately model the enzyme–substrate complex displaying the stereoselectivity that we observed. Two enzymes, YDR368w and YHR104w, were chosen for the scale up and synthesis of fosfomycin and its trans-(1S,2S)-diastereomer

Physical versus psychological social stress in male rats reveals distinct cardiovascular, inflammatory and behavioral consequences

<div><p>Repeated exposure to social stress can precipitate the development of psychosocial disorders including depression and comorbid cardiovascular disease. While a major component of social stress often encompasses physical interactions, purely psychological stressors (i.e. witnessing a traumatic event) also fall under the scope of social stress. The current study determined whether the acute stress response and susceptibility to stress-related consequences differed based on whether the stressor consisted of physical versus purely psychological social stress. Using a modified resident-intruder paradigm, male rats were either directly exposed to repeated social defeat stress (intruder) or witnessed a male rat being defeated. Cardiovascular parameters, behavioral anhedonia, and inflammatory cytokines in plasma and the stress-sensitive locus coeruleus were compared between intruder, witness, and control rats. Surprisingly intruders and witnesses exhibited nearly identical increases in mean arterial pressure and heart rate during acute and repeated stress exposures, yet only intruders exhibited stress-induced arrhythmias. Furthermore, re-exposure to the stress environment in the absence of the resident produced robust pressor and tachycardic responses in both stress conditions indicating the robust and enduring nature of social stress. In contrast, the long-term consequences of these stressors were distinct. Intruders were characterized by enhanced inflammatory sensitivity in plasma, while witnesses were characterized by the emergence of depressive-like anhedonia, transient increases in systolic blood pressure and plasma levels of tissue inhibitor of metalloproteinase. The current study highlights that while the acute cardiovascular responses to stress were identical between intruders and witnesses, these stressors produced distinct differences in the enduring consequences to stress, suggesting that witness stress may be more likely to produce long-term cardiovascular dysfunction and comorbid behavioral anhedonia while exposure to physical stressors may bias the system towards sensitivity to inflammatory disorders.</p></div

Inflammatory-related protein concentrations in the LC and plasma in response to contextual re-exposure.

<p>Inflammatory-related protein concentrations in the LC and plasma in response to contextual re-exposure.</p

Study design and timeline.

<p>Rats were implanted with cardiovascular (CV) radio-telemetric transmitters 10 days prior (D -10) to the start of stress manipulation. Baseline CV measurements were collected for 2 days (D -2—D 0) prior to the start of the daily control, defeat, or witness stress exposure and continued for 3 days post stress/control. Sucrose preference tests were administered 2 days prior to (D -1) and 5 after (D 10) stress manipulations to determine changes in hedonic behavior. On the day of sacrifice (D 11) all rats were exposed to a 15-minute contextual re-exposure.</p

The long-term changes in resting blood pressure and heart rate induced by social stress exposure.

<p>Dark cycle systolic pressure increased across the duration of the study (A). This effect was moderately enhanced in witness rats on days 4 and 6 compared to control and intruder rats, respectively. Conversely, heart rate (HR) measured during the dark cycle was significantly reduced in intruder rats across the duration of the study, compared to both witness and control animals (B). *p<0.05 witness vs. intruder; ^#p<0.05 witness vs. control; ^αp<0.05 control vs. intruder.</p