Adariana Feliciano-Quiñones¹ , Lubriel Sambolin-Escobales ¹ , Cristina Suarez-Gomez ¹ ,

Lizmarie Tirado-Castro ¹, Wilfred Fonseca-Ferrer² , Kimberly Santos-Aviles¹,

Maria Colon-Romero¹ , Anixa Hernández-Lopez¹ , James Porter ¹

1 Ponce Health Sciences University, Ponce Research Institute, Ponce, PR

2 University of Puerto Rico, Ponce, PR


Previous data showed that rats with depressive-like behavior showed increased concentration of C20 ceramides in serum. Moreover, depressive-like behavior has been associated with increased microglia and the production of inflammatory mediators. However, it is unclear whether increasing C20 ceramides in the brain is sufficient to induce depressive-like behaviors and activate microglia and astrocytes, which could induce localized production of inflammatory mediators. Therefore, we hypothesized that infusion of C20 ceramides into the ventral hippocampus (VH) of rats would activate microglia and astrocytes to induce depressive-like symptoms. To test this hypothesis, adult male and female rats received 7 single infusions of C20 ceramide or vehicle into the VH every 48 hours to assess short-term behavioral changes. Twentyfour hours after each C20 ceramide infusion, a sucrose preference test (SPT) was used to determine changes in anhedonia-like behavior. Animals injected with C20 ceramides showed less preference for sucrose, suggesting increased anhedonia-like behavior. Five days after the last infusion of C20, a sucrose grooming test (SGT) and forced swim test (FST) were performed to examine long-term changes in anhedonia and depressive-like behaviors. All groups showed similar behavior in the SGT and the FST, suggesting that behavioral changes induced by the C20ceramide infusions were reversible. Animals were sacrificed after the final FST, and immunofluorescence staining was performed to determine the expression of Iba-1 and GFAP to assess microglia and astrocyte activation. The infusion of C20 ceramides increased the number of microglial cells in the VH, but no changes were noted in the expression of astrocytes. In conclusion, our data suggest that the localized presence of C20 ceramides in the VH of rats is sufficient to cause short-term reversible behavioral changes and activate microglia.

Supported By: NIH-NIGMS 2R25GM082406 (PHSU RISE Graduate Training Program), NIM-HD

MD007579 (B.R.A.I.N. and M.A.G.I.C. Core), NIH-NIGMS R15MH116345, and NIH-NIGMS

R25GM096955 (UPR-Ponce PRISE Program).

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