title: Protective function of nicotinamide against ketamine-induced apoptotic neurodegeneration in the infant rat brain.
abstract: During development, anesthetics activate neuroapoptosis and produce damage in the central nervous system that leads to several types of neurological disorders. A single dose of ketamine (40 mg/kg) during synaptogenesis in a 7-day-old rat brain activated the apoptotic cascade and caused extensive neuronal cell death in the forebrain. In this study, we investigated the protective effect of nicotinamide against ketamine-induced apoptotic neurodegeneration. After 4 h, neuronal cell death induced by ketamine was associated with the induction of Bax, release of cytochrome c into the cytosol, and activation of caspase-3. One single dose of 1 mg/g nicotinamide was administered to a developing rat and was found to inhibit ketamine-induced neuroapoptosis by downregulating Bax, inhibiting cytochrome c release from mitochondria into cytosol, and inhibiting the expression of activated caspase-3. TUNEL and immunohistochemical analyses showed that ketamine-induced cell death occurred through apoptosis and that it was inhibited by nicotinamide. Fluoro-Jade-B staining demonstrated an increased number of dead cells in the cortex and thalamus after ketamine treatment; treatment with nicotinamide reduced the number of dead cells in these brain regions. Our findings suggest that nicotinamide attenuated ketamine-induced neuronal cell loss in the developing rat brain and is a promising therapeutic and neuroprotective agent for the treatment of neurodevelopmental disorders.
authors.affiliation: Department of Biology, College of Natural Sciences-RINS and Applied Life Science-Brain Korea 21, Gyeongsang National University, Chinju 660-701, Republic of Korea.
authors.forename: Najeeb
authors.initials: N
authors.lastname: Ullah
authors.forename: Ikram
authors.initials: I
authors.lastname: Ullah
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Naseer
authors.forename: Park Moon
authors.initials: PM
authors.lastname: Seok
authors.forename: Jawad
authors.initials: J
authors.lastname: Ahmed
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
mesh_terms: D000778:Anesthetics, Dissociative / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D007649:Ketamine / Q000633:toxicity*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009536:Niacinamide / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D000778:Anesthetics, Dissociative; D018696:Neuroprotective Agents; D014803:Vitamin B Complex; D009536:Niacinamide; D007649:Ketamine