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MCP-1 and MIP-3 Expression in LCR/HCR RatsDr. Anuska Andjelkovic Lab By: Zarion Marshall

Low Capacity Runners (LCR) and High Capacity Runners (HCR) RatsLCR rats are highly susceptible to cardiovascular diseases like atherosclerosisLCR rats are insulin resistant Natural screening model (no gene manipulation)Grouped by simple measure of treadmill running distance

My RatsGeneration 23About 46-48 weeks old (~10-11 months)All female for lower variability of body weight

LCR more sensitive to harmful effects of high fat dietOverall high body weightHigher fat percentageHigher food intakeHigher serum leptin levels (mostly adipose)

Credit: Colleen M. Novak, Carlos Escande, Paul R. Burghardt, Minzhi Zhang, Maria Teresa Barbosa, Eduardo N. Chini, Steven L. Britton, Lauren G. Koch, Huda Akil, James A. Levine in Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity

Activity and Energy ExpenditureLCR less active (not dependent on body weight) and expend less energy

Credit: Colleen M. Novak, Carlos Escande, Paul R. Burghardt, Minzhi Zhang, Maria Teresa Barbosa, Eduardo N. Chini, Steven L. Britton, Lauren G. Koch, Huda Akil, James A. Levine in Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity

Energy Expenditure and Respiratory Exchange Rate (RER)LCR lower energy expenditure even in restAlso higher RER which suggests ineffecient use of lipids

Credit: Colleen M. Novak, Carlos Escande, Paul R. Burghardt, Minzhi Zhang, Maria Teresa Barbosa, Eduardo N. Chini, Steven L. Britton, Lauren G. Koch, Huda Akil, James A. Levine in Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity

HypothesisLCR rats are most susceptible to proinflammatory factors which leaves the blood brain barrier (BBB) at risk for microvascular changes like strokeChemokines on basolateral (brain) side of barrier attract leukocytes from the apical (blood) sideGoalInvestigate the chemokines monocyte chemotactic protein (MCP-1) and macrophage inflammatory protein (MIP-3) and their role in the BBBs integrity

Blood Brain Barrier

How It Works (Supposedly) Proinflammatory proteins cause barrier to lose integrity between endothelial cells

Protein Array (Vessels)Leptin 349.6763.580.181829LIX308.76984.773.189435L-Selectin192.28603.063.136364MCP-1311.311,782.955.727249MIP-339.78779.8719.60458MMP-8144.55383.522.6532PDGF-AA4,323.153,028.130.700445Prolactin R4,737.595,581.021.178029RAGE3,582.806,503.181.815111Thymus Chemokine-14,596.717,274.251.582491TIMP-1178.61982.75.501932

HCRLCRHCRLCR

Cytokine Expression

MCP-1(Tissue ELISA)0.03 ng/ml HCR1.12 ng/ml LCR

MIP-3 (Tissue ELISA)0.14 pg/ml HCR2.72 pg/ml LCR

Staining Red=chemokine Green=astrocyteMIP-3 seems to be mostly in astrocytes You can see from the staining as well not as much of either in HCRWe think MCP-1 is more in microglia

LCRHCRMCP-1MIP-3

ConclusionThe higher inflammatory risk of LCR rats explains at least in part their phenotype which resembles classic metabolic syndrome conditionsMCP-1 and MIP-3 contribute are indeed factors that differentiate the two LCR and HCR phenotypes and suggests that a role in microvascular changes

Much Thanks toSvetlana and Nikola And of course Dr. Andjelkovic