NAD+ Attenuates Bilirubin-Induced Hyperexcitation in the Ventral Cochlear Nucleus by Inhibiting Excitatory Neurotransmission and Neuronal Excitability

• DOI: 10.3389/fncel.2017.00021
• Publication Date: 2017-02-02T22:36:11Z
• Authors: Min Liang; Xin-Lu Yin; Lu-Yang Wang; Wei-Hai Yin; Ning-Ying Song; Hai-Bo Shi; Chun-Yan Li; Shan-Kai Yin
• Keywords: ventral cochlear nucleus; 0303 health sciences; 03 medical and health sciences; hyperexcitation; evoked EPSCs (eEPSCs); bilirubin encephalopathy; spontaneous spike; nicotinamide adenine dinucleotide (NAD+); patch-clamp recording; miniature excitatory postsynaptic currents (mEPSCs); Neuroscience; 3. Good health

Nicotinamide adenine dinucleotide (NAD+) is an important molecule with extensive biological functions in various cellular processes, including protection against cell injuries. However, little known regarding the roles of NAD+ neuronal excitation and excitotoxicity associated many neurodegenerative disorders diseases. Using patch-clamp recordings, we studied its potential effects on principal neurons ventral cochlear nucleus (VCN), which particularly vulnerable to bilirubin excitotoxicity. We found that effectively decreased size evoked excitatory postsynaptic currents (eEPSCs), increased paired-pulse ratio (PPR), reversed effect eEPSCs, implicating inhibitory presynaptic release probability (Pr). Moreover, not only basal frequency miniature EPSCs (mEPSCs), but also bilirubin-induced increases mEPSCs without affecting their amplitude under either condition. Furthermore, spontaneous firing VCN as well frequency. Whole-cell current-clamp recordings showed could directly decrease intrinsic excitability presence synaptic blockers, suggesting exerts actions both loci. Consistent these observations, latency first spike triggered by high-frequency train stimulation afferents (i.e. auditory nerve) was prolonged NAD+. These results collectively indicate suppresses transmitter excitability, jointly weakening neurotransmission. Our findings provide a basis for exploration prevention treatment encephalopathy other neurological disorders.