Robust changes in expression of brain-derived neurotrophic factor (BDNF) mRNA and protein across the brain do not translate to detectable changes in BDNF levels in CSF or plasma.
Adult rats were treated acutely with peripheral kainic acid (KA), and changes in brain-derived neurotrophic factor (BDNF) mRNA and protein were tracked over time across multiple brain regions. Despite robust elevation in both mRNA and protein in multiple brain regions, plasma BDNF was unchanged and cerebrospinal fluid (CSF) BDNF levels remained undetectable. Primary neurons were then treated with KA. BDNF was similarly elevated within neurons, but was undetectable in neuronal media. Thus, while deficits in BDNF signaling have been implicated in a number of diseases, these data suggest that extracellular concentrations of BDNF may not be a facile biomarker for changes in neurons.
Pfizer Global Research and Development, Groton, CT 06340, USA. thomas.a.lanz@pfizer.com
Thomas A
TA
Lanz
Susan E
SE
Bove
Catherine D
CD
Pilsmaker
Abigail
A
Mariga
Elena M
EM
Drummond
Gregory W
GW
Cadelina
Wendy O
WO
Adamowicz
Brentt J
BJ
Swetter
Sharon
S
Carmel
Jo Ann
JA
Dumin
Robin J
RJ
Kleiman
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood* / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000473:pathology; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007608:Kainic Acid; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000097:blood / Q000134:cerebrospinal fluid / Q000139:chemically induced
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D007770:L-Lactate Dehydrogenase; D007608:Kainic Acid