Intranasally delivered TGF-beta1 enters brain and regulates gene expressions of its receptors in rats.
This study is aimed to evaluate the brain distribution of transforming growth factor-beta1 (TGF-beta1) following intranasal administration and the subsequent biological effects of TGF-beta1. Adult rats were given recombinant human TGF-beta1 (rhTGF-beta1) or vehicle solution intranasally. TGF-beta1 concentrations were significantly raised in several brain regions and the trigeminal nerve following intranasal delivery. The elevation appeared within 30 min and was sustained for at least 6 h, reaching its greatest level at 60 min. A concentration gradient in the central nervous system (CNS) regions was produced during the first 2 h after intranasal administration, with the OB presenting a significantly higher concentration than any other CNS regions. The nasally administered TGF-beta1 subsequently regulated gene expressions of its two receptors (TGF-beta receptor types I and II) in vivo, but did not affect mRNA level of TGF-beta1 itself. Our results suggest that TGF-beta1 can be transported into the CNS via the olfactory and trigeminal pathways, and may consequently exert its biological effects by regulating gene expressions of its receptors. Intranasal administration of neurotrophic factors may offer a potential strategy for treating some CNS disorders.
Ma
Yu-Ping
YP
Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305# East Zhongshan Road, Nanjing 210002, Jiangsu Province, People's Republic of China.
Ma
Min-Min
MM
Ge
Song
S
Guo
Rui-Bing
RB
Zhang
Hua-Jun
HJ
Frey
William H
WH
Xu
Ge-Lin
GL
Liu
Xin-Feng
XF
D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage*
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1