title: Beneficial impact of intracerebroventricular fractalkine administration on behavioral and biochemical changes induced by prenatal stress in adult rats: Possible role of NLRP3 inflammasome pathway.
abstract: Several lines of evidence indicate that adverse experience in early life may be a triggering factor for pathological inflammatory processes and lead to the development of depression. Fractalkine (CX3CL1), a chemokine, plays an important role not only in the migration, differentiation and proliferation of neuronal and glial cells but also in the regulation of neuronal-microglial signaling and the production of pro-inflammatory factors. In the present study, we examined the impact of a prenatal stress procedure on the expression of fractalkine in the hippocampus and frontal cortex of young and adult male rats. Furthermore, we measured the age-dependent effect of stress during pregnancy on the expression of pro-inflammatory factors IL-1β, IL-18, TNF-α, IL-6, and CCL2 in both brain structures. Next, to illustrate the link between fractalkine signaling and the behavioral and biochemical changes induced by prenatal stress, adult prenatally stressed offspring were injected intracerebroventricularly (icv) with exogenous fractalkine. We reported that prenatal stress leads to long-lasting deficits in fractalkine signaling and enhanced inflammatory activation. The study demonstrates that icv administration of fractalkine attenuates the behavioural changes evoked by prenatal stress procedure in adult animals. Moreover, fractalkine administration, exhibits anti-inflammatory action, mainly in the frontal cortex of adult prenatally stressed rats. The effect of fractalkine is related to inhibition of NLRP3 inflammasome. However, its action on the other members of NOD-like receptor family (NLR) cannot be excluded. These findings provide new in vivo evidence that the behavioral and inflammatory disturbances observed in adult prenatally stressed rats may be related to long-lasting malfunctions in fractalkine signaling.
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ślusarczyk
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Trojan
authors.affiliation: Laboratory of Drug Addiction, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Wydra
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Głombik
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Chamera
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kucharczyk
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
authors.forename: Bogusława
authors.initials: B
authors.lastname: Budziszewska
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kubera
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
authors.forename: Władysław
authors.initials: W
authors.lastname: Lasoń
authors.affiliation: Laboratory of Drug Addiction, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland. Electronic address: basta@if-pan.krakow.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Basta-Kaim
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D054428:Chemokine CX3CL1 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000254:growth & development / Q000276:immunology / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000378:metabolism* / Q000523:psychology; D012333:RNA, Messenger / Q000235:genetics; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology / Q000378:metabolism*
chemical_list: D054428:Chemokine CX3CL1; D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D012333:RNA, Messenger
keywords: Brain; Fractalkine (CX3CL1); Inflammation; NLRP3 inflammasome; Prenatal stress