Human temporal lobe epilepsy (TLE) is associated with bioenergetic abnormaliti es including decreased phosphocreatine (PCr) normalized to ATP. The physiologica l consequences of these metabolic alterations have not be...Human temporal lobe epilepsy (TLE) is associated with bioenergetic abnormaliti es including decreased phosphocreatine (PCr) normalized to ATP. The physiologica l consequences of these metabolic alterations have not been established.We hypot hesized that impaired bioenergetics would correlate with alterations in physiolo gical functions under conditions that strongly activate neural metabolism. We co rrelated several physiological variables obtained from epileptic human dentate g ranule cells studied in slices with hippocampal PCr/ATP measured using in vivo m agnetic resonance spectroscopy.The physiological variables included: the ability to fire multiple action potentials in response to single stimuli,the inhibitory postsynaptic potential (IPSP) conductance and the responses to a 10 Hz, 10 s st imulus train. We noted a significant negative correlation between the ability to fire multiple spikes in response to single synaptic stimulation and PCr/ATP (P < 0.03) and a positive correlation between the IPSP conductance and PCr/ATP (P < 0.05). Finally, there was a strong correlation between PCr/ATP and the recovery of the membrane potential following a stimulus train (P < 0.01), with low PCr/A TP being associated with prolonged recovery times. These data suggest that the b ioenergetic impairment seen in this tissue is associated with specific changes i n excitatory and inhibitory neuronal responses to synchronized synaptic inputs.展开更多
文摘Human temporal lobe epilepsy (TLE) is associated with bioenergetic abnormaliti es including decreased phosphocreatine (PCr) normalized to ATP. The physiologica l consequences of these metabolic alterations have not been established.We hypot hesized that impaired bioenergetics would correlate with alterations in physiolo gical functions under conditions that strongly activate neural metabolism. We co rrelated several physiological variables obtained from epileptic human dentate g ranule cells studied in slices with hippocampal PCr/ATP measured using in vivo m agnetic resonance spectroscopy.The physiological variables included: the ability to fire multiple action potentials in response to single stimuli,the inhibitory postsynaptic potential (IPSP) conductance and the responses to a 10 Hz, 10 s st imulus train. We noted a significant negative correlation between the ability to fire multiple spikes in response to single synaptic stimulation and PCr/ATP (P < 0.03) and a positive correlation between the IPSP conductance and PCr/ATP (P < 0.05). Finally, there was a strong correlation between PCr/ATP and the recovery of the membrane potential following a stimulus train (P < 0.01), with low PCr/A TP being associated with prolonged recovery times. These data suggest that the b ioenergetic impairment seen in this tissue is associated with specific changes i n excitatory and inhibitory neuronal responses to synchronized synaptic inputs.
基金supported by grants from the National Key Research and Development Program of China(No.2018YFA0108000)the National Natural Science Foundation of China(No.31970971,31771196,31471037)+3 种基金Shanghai Commission of Health Youth Program(No.2017YQ016)Shanghai Rising-Star Program(No.18QA1400600)Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01)ZJLab。
