Effects of lithium and valproic acid on BDNF protein and gene expression in an in vitro human neuron-like model of degeneration.
One of the common effects of lithium (Li) and valproic acid (VPA) is their ability to protect against excitotoxic insults. Neurodegenerative and neuropsychiatric diseases may be also associated with altered trophic support of brain-derived neurotrophic factor (BDNF), the most widely distributed neurotrophin in the central nervous system. However, despite these evidences, the effect of Li-VPA combination on BDNF after excitoxic insult has been inadequately investigated. We address this issue by exposing a human neuroblastoma cell line (SH-SY5Y) to neurotoxic concentration of L-glutamate and exploring whether the neuroprotective action of Li-VPA on these cells is associated with changes in BDNF protein and mRNA levels. The results showed that pre-incubation of Li-VPA abolished the toxic effect of glutamate on SH-SY5Y cell survival and this neuroprotective effect was associated with increased synthesis and mRNA expression of BDNF after 24 and 48 h of incubation. In conclusion, this study demonstrates that the neuroprotective effects of Li-VPA against glutamate-induced neurotoxicity in SH-SY5Y neuroblastoma cells is associated with increased synthesis and mRNA expression of BDNF. These data further support the idea that these two drugs can be used for prevention and/or treatment of glutamate-related neurodegenerative disorders.
IRCCS Santa Lucia Foundation, Rome, Italy Department of Internal Medicine, Tor Vergata University, Rome, Italy.
Nicoletta
N
Croce
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Aleksander A
AA
Mathé
IRCCS Santa Lucia Foundation, Rome, Italy Department of Systemic Medicine, Tor Vergata University, Rome, Italy.
Francesca
F
Gelfo
IRCCS Santa Lucia Foundation, Rome, Italy Department of Systemic Medicine, Tor Vergata University, Rome, Italy.
Carlo
C
Caltagirone
Department of Internal Medicine, Tor Vergata University, Rome, Italy.
Sergio
S
Bernardini
IRCCS Santa Lucia Foundation, Rome, Italy f.angelucci@hsantalucia.it.
Francesco
F
Angelucci
D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000633:toxicity; D006801:Humans; D016651:Lithium Carbonate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology*
D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D016651:Lithium Carbonate; D018698:Glutamic Acid; D014635:Valproic Acid
BDNF; L-glutamate; Lithium; SH-SY5Y; excitotoxicity; neuronal survival; valproic acid