Effects of FGF receptor peptide agonists on animal behavior under normal and pathological conditions.
Hexafins are recently identified low-molecular-weight peptide agonists of the fibroblast growth factor receptor (FGFR), derived from the beta6-beta7 loop region of various FGFs. Synthetic hexafin peptides have been shown to bind to and induce tyrosine phosphorylation of FGFR1, stimulate neurite outgrowth, and promote neuronal survival in vitro. Thus, the pronounced biological activities of hexafins in vitro make them attractive compounds for pharmacological studies in vivo. The present study investigated the effects of subcutaneous administration of hexafin1 and hexafin2 (peptides derived from FGF1 and FGF2, respectively) on social memory, exploratory activity, and anxiety-like behavior in adult rats. Treatment with hexafin1 and hexafin2 resulted in prolonged retention of social memory. Furthermore, rats treated with hexafin2 exhibited decreased anxiety-like behavior in the elevated plus maze. Employing an R6/2 mouse model of Huntington's disease (HD), we found that although hexafin2 did not affect the progression of motor symptoms, it alleviated deficits in activity related to social behavior, including sociability and social novelty. Thus, hexafin2 may have therapeutic potential for the treatment of HD.
Rudenko
Olga
O
Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark. rudenko@sund.ku.dk
Tkach
Vadim
V
Berezin
Vladimir
V
Bock
Elisabeth
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D016220:Fibroblast Growth Factor 1 / Q000138:chemical synthesis / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000138:chemical synthesis / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000819:agonists* / Q000502:physiology; D006801:Humans; D007279:Injections, Subcutaneous / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D010455:Peptides / Q000819:agonists* / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000819:agonists* / Q000502:physiology
D010446:Peptide Fragments; D010455:Peptides; D017468:Receptors, Fibroblast Growth Factor; C557087:hexafin1 peptide; C557088:hexafin2 peptide; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors