Circadian behaviour in neuroglobin deficient mice

TY - JOUR

T1 - Circadian behaviour in neuroglobin deficient mice

AU - Hundahl, Christian A

AU - Fahrenkrug, Jan

AU - Hay-Schmidt, Anders

AU - Georg, Birgitte

AU - Faltoft, Birgitte

AU - Hannibal, Jens

PY - 2012/4/5

Y1 - 2012/4/5

N2 - Neuroglobin (Ngb), a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN). The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP) and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night.

AB - Neuroglobin (Ngb), a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN). The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP) and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night.

KW - Animals

KW - Behavior, Animal

KW - Blotting, Western

KW - Circadian Rhythm

KW - Female

KW - Fluorescent Antibody Technique

KW - Globins

KW - Immunoenzyme Techniques

KW - Immunoprecipitation

KW - Light

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Nerve Tissue Proteins

KW - Neurons

KW - Period Circadian Proteins

KW - Proto-Oncogene Proteins c-fos

KW - RNA, Messenger

KW - Rats

KW - Real-Time Polymerase Chain Reaction

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Suprachiasmatic Nucleus

KW - Synapses

U2 - 10.1371/journal.pone.0034462

DO - 10.1371/journal.pone.0034462

M3 - Journal article

C2 - 22496809

SN - 1932-6203

VL - 7

SP - e34462

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 4

ER -