Prenatal Alcohol Exposure in Rats Diminishes Postnatal Cxcl16 Chemokine Ligand Brain Expression

Abstract

Maternal ethanol consumption during pregnancy is one of the main causes of Neurodevelopmental disorders (NDD). Prenatal alcohol exposure (PAE) produces several adverse manifestations. Even low or moderate intake has been associated with long-lasting behavioral and cognitive impairment in offspring. In this study we examined the gene expression profile in the rat nucleus accumbens using microarrays, comparing animals exposed prenatally to ethanol and controls. Microarray gene expression showed an overall downward regulatory effect of PAE. Gene cluster analysis reveals that the gene groups most affected are related to transcription regulation, transcription factors and homeobox genes. We focus on the expression of the C-X-C motif chemokine ligand 16 (Cxcl16) which was differentially expressed. There is a significant reduction in the expression of this chemokine throughout the brain under PAE conditions, evidenced here by quantitative polymerase chain reaction qPCR and immunohistochemistry. Chemokines are involved in neuroprotection and implicated in alcohol-induced brain damage and neuroinflammation in the developing central nervous system (CNS), therefore, the significance of the overall decrease in Cxcl16 expression in the brain as a consequence of PAE may reflect a reduced ability in neuroprotection against subsequent conditions, such as excitotoxic damage, inflammatory processes or even hypoxic-ischemic insult.

Central and Peripheral Inflammation: A Common Factor Causing Addictive and Neurological Disorders and Aging-Related Pathologies

“…Indeed, rats exposed prenatally to ethanol (between gestational days 8 to 20) had a structural modification of the ventral tegmental area (VTA) microglia where a reduction in microglial branch and junction numbers [ 141 ] was observed. In addition, prenatal ethanol exposure induced a reduction in the protein expression of Fkbp5 (an immunophilin protein) and Cxcl16 (a mediator of innate immunity) in the NAc [ 142 ]. In this context, the expression of Cxcl16 is induced by inflammatory cytokines such as IFN-γ and TNF-α [ 143 ], suggesting a compensatory effect in the offspring to deal with inflammation.…”

Cellular, synaptic, and network effects of chemokines in the central nervous system and their implications to behavior

“…Considering expression in the CNS, CXCL16, together with its unique receptor CXCR6, is constitutively expressed in distinct CNS cells (see Table 1 ), further highlighting their involvement in mediating cell-to-cell communication or synaptic transmission (see also: 2.2.1, [ 40 ]). Their effects in the CNS are still largely unexplored; however, recently, CXCL16/CXCR6 expression changes are becoming associated with prenatal alcohol consumption [ 41 ] or mild traumatic brain injury [ 42 ].…”