The circadian hippocampus and its reprogramming in epilepsy: impact for chronotherapeutics

Gene and protein expression displays circadian oscillations in numerous body organs. These oscillations can be disrupted in diseases, thus contributing to the disease pathology. Whether the molecular architecture of cortical brain regions oscillates daily and whether these oscillations are modified in brain disorders is less understood. We identified 1200 daily oscillating transcripts in the hippocampus of control mice. More transcripts (1600) were oscillating in experimental epilepsy, with only one fourth oscillating in both conditions. Proteomics confirmed these results. Metabolic activity and targets of antiepileptic drugs displayed different circadian regulation in control and epilepsy. Hence, the hippocampus, and perhaps other cortical regions, shows a daily remapping of its molecular landscape, which would enable different functioning modes during the night/day cycle. The impact of this remapping in brain pathologies needs to be taken into account not only to study their mechanisms, but also to design drug treatments and time their delivery.

[1]  D. Holtzman,et al.  Mechanisms linking circadian clocks, sleep, and neurodegeneration , 2016, Science.

[2]  Marcello Massimini,et al.  Circadian regulation of human cortical excitability , 2016, Nature Communications.

[3]  W. Löscher,et al.  Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet. , 2016, Cold Spring Harbor perspectives in medicine.

[4]  D. Gitaí,et al.  Diurnal Variation Has Effect on Differential Gene Expression Analysis in the Hippocampus of the Pilocarpine-Induced Model of Mesial Temporal Lobe Epilepsy , 2015, PloS one.

[5]  Pierre Baldi,et al.  The pervasiveness and plasticity of circadian oscillations: the coupled circadian-oscillators framework , 2015, Bioinform..

[6]  R. Spencer,et al.  Variations in Phase and Amplitude of Rhythmic Clock Gene Expression across Prefrontal Cortex, Hippocampus, Amygdala, and Hypothalamic Paraventricular and Suprachiasmatic Nuclei of Male and Female Rats , 2015, Journal of biological rhythms.

[7]  F. Bartolomei,et al.  Predicting and treating stress‐Induced vulnerability to epilepsy and depression , 2015, Annals of neurology.

[8]  N. McNaughton,et al.  The frequency of hippocampal theta rhythm is modulated on a circadian period and is entrained by food availability , 2015, Front. Behav. Neurosci..

[9]  D. Turner,et al.  Metabolic responses differentiate between interictal, ictal and persistent epileptiform activity in intact, immature hippocampus in vitro , 2015, Neurobiology of Disease.

[10]  M. Hughes,et al.  A circadian gene expression atlas in mammals: Implications for biology and medicine , 2014, Proceedings of the National Academy of Sciences.

[11]  W. Stacey,et al.  On the nature of seizure dynamics. , 2014, Brain : a journal of neurology.

[12]  S. Amir,et al.  Phase Differences in Expression of Circadian Clock Genes in the Central Nucleus of the Amygdala, Dentate Gyrus, and Suprachiasmatic Nucleus in the Rat , 2014, PloS one.

[13]  L. Kriegsfeld,et al.  Circadian rhythms have broad implications for understanding brain and behavior , 2014, The European journal of neuroscience.

[14]  Ilia N. Karatsoreos,et al.  Links between Circadian Rhythms and Psychiatric Disease , 2014, Front. Behav. Neurosci..

[15]  B. Smarr,et al.  A time to remember: the role of circadian clocks in learning and memory. , 2014, Behavioral neuroscience.

[16]  P. Sassone-Corsi,et al.  Epigenetic control and the circadian clock: Linking metabolism to neuronal responses , 2014, Neuroscience.

[17]  Robert J. McDonald,et al.  Neuroscience and Biobehavioral Reviews the Trouble with Circadian Clock Dysfunction: Multiple Deleterious Effects on the Brain and Body , 2022 .

[18]  David S. Wishart,et al.  DrugBank 4.0: shedding new light on drug metabolism , 2013, Nucleic Acids Res..

[19]  I. Blümcke,et al.  Epigenetic mechanisms in epilepsy. , 2014, Progress in brain research.

[20]  Pierre Baldi,et al.  Reprogramming of the Circadian Clock by Nutritional Challenge , 2013, Cell.

[21]  W. Löscher,et al.  Pilocarpine-induced epilepsy in mice alters seizure thresholds and the efficacy of antiepileptic drugs in the 6-Hertz psychomotor seizure model , 2013, Epilepsy Research.

[22]  K. Dębski,et al.  Alterations in miRNA Levels in the Dentate Gyrus in Epileptic Rats , 2013, PloS one.

[23]  S. Amir,et al.  Comprehensive Mapping of Regional Expression of the Clock Protein PERIOD2 in Rat Forebrain across the 24-h Day , 2013, PloS one.

[24]  Mark R. Bower,et al.  Do Seizures in the Pilocarpine Model Start in the Hippocampal Formation? , 2014, Epilepsy currents.

[25]  R. Myers,et al.  Circadian patterns of gene expression in the human brain and disruption in major depressive disorder , 2013, Proceedings of the National Academy of Sciences.

[26]  Paolo Sassone-Corsi,et al.  The circadian clock: a framework linking metabolism, epigenetics and neuronal function , 2012, Nature Reviews Neuroscience.

[27]  P. Sassone-Corsi,et al.  Metabolism and the circadian clock converge. , 2013, Physiological reviews.

[28]  Data production leads,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .

[29]  Pierre Baldi,et al.  CircadiOmics: integrating circadian genomics, transcriptomics, proteomics and metabolomics , 2012, Nature Methods.

[30]  Ramón Doallo,et al.  CircadiOmics: integrating circadian genomics, transcriptomics, proteomics and metabolomics , 2012, Nature Methods.

[31]  ENCODEConsortium,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[32]  D. Bilkey,et al.  The firing rate of hippocampal CA1 place cells is modulated with a circadian period , 2012, Hippocampus.

[33]  Pierre Baldi,et al.  Cyber-T web server: differential analysis of high-throughput data , 2012, Nucleic Acids Res..

[34]  C. Bernard,et al.  Differential Dorso-ventral Distributions of Kv4.2 and HCN Proteins Confer Distinct Integrative Properties to Hippocampal CA1 Pyramidal Cell Distal Dendrites* , 2012, The Journal of Biological Chemistry.

[35]  Xiaohui Xie,et al.  MotifMap: integrative genome-wide maps of regulatory motif sites for model species , 2011, BMC Bioinformatics.

[36]  A. de Weerd,et al.  Sleep disturbances in people with epilepsy; prevalence, impact and treatment. , 2011, Sleep medicine reviews.

[37]  C. Bernard,et al.  Neuron‐restrictive silencer factor‐mediated hyperpolarization‐activated cyclic nucleotide gated channelopathy in experimental temporal lobe epilepsy , 2011, Annals of neurology.

[38]  Jaak Vilo,et al.  g:Profiler—a web server for functional interpretation of gene lists (2011 update) , 2011, Nucleic Acids Res..

[39]  Michele Magrane,et al.  UniProt Knowledgebase: a hub of integrated protein data , 2011, Database J. Biol. Databases Curation.

[40]  W. Löscher,et al.  Enhanced susceptibility to the GABA antagonist pentylenetetrazole during the latent period following a pilocarpine-induced status epilepticus in rats , 2011, Neuropharmacology.

[41]  Karl Kornacker,et al.  JTK_CYCLE: An Efficient Nonparametric Algorithm for Detecting Rhythmic Components in Genome-Scale Data Sets , 2010, Journal of biological rhythms.

[42]  Rafael A. Irizarry,et al.  A framework for oligonucleotide microarray preprocessing , 2010, Bioinform..

[43]  L. Lyons,et al.  Cycling Behavior and Memory Formation , 2009, The Journal of Neuroscience.

[44]  D. Welsh,et al.  Expression of the circadian clock gene Period2 in the hippocampus: possible implications for synaptic plasticity and learned behaviour , 2009, ASN neuro.

[45]  W. Löscher.  Preclinical assessment of proconvulsant drug activity and its relevance for predicting adverse events in humans. , 2009, European journal of pharmacology.

[46]  Xiaohui Xie,et al.  MotifMap: a human genome-wide map of candidate regulatory motif sites , 2009, Bioinform..

[47]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[48]  Allan R. Jones,et al.  Genomic Anatomy of the Hippocampus , 2008, Neuron.

[49]  Sung Han,et al.  Circadian oscillation of hippocampal MAPK activity and cAMP: implications for memory persistence , 2008, Nature Neuroscience.

[50]  Y. Xing,et al.  A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function , 2008, The Journal of Neuroscience.

[51]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[52]  William Stafford Noble,et al.  Assigning significance to peptides identified by tandem mass spectrometry using decoy databases. , 2008, Journal of proteome research.

[53]  Kai Wang,et al.  Genome-wide expression profiling and bioinformatics analysis of diurnally regulated genes in the mouse prefrontal cortex , 2007, Genome Biology.

[54]  Clare Guilding,et al.  Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain? , 2007, The European journal of neuroscience.

[55]  Hedi Peterson,et al.  g:Profiler—a web-based toolset for functional profiling of gene lists from large-scale experiments , 2007, Nucleic Acids Res..

[56]  Avraham Mayevsky,et al.  Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies. , 2007 .

[57]  Jakub Otáhal,et al.  Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from chronic epileptic rats and humans. , 2005, Brain : a journal of neurology.

[58]  Christopher S. Colwell,et al.  Circadian Regulation of Hippocampal Long-Term Potentiation , 2005, Journal of biological rhythms.

[59]  J. Takahashi,et al.  Circadian Rhythm Generation and Entrainment in Astrocytes , 2005, The Journal of Neuroscience.

[60]  D. Johnston,et al.  Acquired Dendritic Channelopathy in Temporal Lobe Epilepsy , 2004, Science.

[61]  Martin Straume,et al.  Temporal distribution of partial seizures: Comparison of an animal model with human partial epilepsy , 1998, Annals of neurology.

[62]  D. Shen,et al.  A timed intravenous pentylenetetrazol infusion seizure model for quantitating the anticonvulsant effect of valproic acid in the rat. , 1985, Journal of pharmacological methods.

[63]  K. Harris,et al.  Age differences in a circadian influence on hippocamapl LTP , 1983, Brain Research.

[64]  B L McNaughton,et al.  Circadian rhythm of synaptic excitability in rat and monkey central nervous system. , 1977, Science.