Fibroblast growth factor 2: Role in prenatal alcohol-induced stimulation of hypothalamic peptide neurons.

Guo-Qing Chang, Nushrat Yasmin, Adam D Collier, Olga Karatayev, Nailya Khalizova, Amanda Onoichenco, Milisia Fam, Avi S Albeg, Samantha Campbell, Sarah F Leibowitz

Progress in neuro-psychopharmacology & biological psychiatry 2022 Jun 08

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Prenatal alcohol exposure (PAE) increases alcohol consumption and risk for alcohol use disorder. This phenomenon in rodents is suggested to involve a stimulatory effect of PAE, in female more than male offspring, on neurogenesis and density of neurons expressing neuropeptides in lateral hypothalamus (LH), including melanin-concentrating hormone (MCH), known to promote alcohol intake. With evidence suggesting a role for fibroblast growth factor 2 (FGF2) and its receptor FGFR1 in stimulating neurogenesis and alcohol drinking, we investigated here whether the FGF2-FGFR1 system is involved in the PAE-induced increase in MCH neurons, in postnatal offspring of pregnant rats given ethanol orally (embryonic day 10-15) at a low-moderate (2 g/kg/day) or high (5 g/kg/day) dose. Our results demonstrate that PAE at the low-moderate but not high dose stimulates FGF2 and FGFR1 gene expression and increases the density of MCH neurons co-expressing FGF2, only in females, but FGFR1 in both sexes. PAE induces this effect in the dorsal but not ventral area of the LH. Further analysis of FGF2 and FGFR1 transcripts within individual MCH neurons reveals an intracellular, sex-dependent effect, with PAE increasing FGF2 transcripts positively related to FGFR1 in the nucleus as well as cytoplasm of females but transcripts only in the cytoplasm of males. Peripheral injection of FGF2 itself (80 μg/kg, s.c.) in pregnant rats mimics these effects of PAE. Together, these results support the involvement of the FGF2-FGFR1 system in mediating the PAE-induced, sex dependent increase in density of MCH neurons, possibly contributing to increased alcohol consumption in the offspring. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Guo-Qing Chang, Nushrat Yasmin, Adam D Collier, Olga Karatayev, Nailya Khalizova, Amanda Onoichenco, Milisia Fam, Avi S Albeg, Samantha Campbell, Sarah F Leibowitz. Fibroblast growth factor 2: Role in prenatal alcohol-induced stimulation of hypothalamic peptide neurons. Progress in neuro-psychopharmacology & biological psychiatry. 2022 Jun 08;116:110536