Biomedical subjects

Hidenobu Ohta

Publications and source records attributed to Hidenobu Ohta.

6 recordsLinked to original sources

PubMed2006

Constant light disrupts the developing mouse biological clock.

The central biological clock of the brain, contained within the suprachiasmatic nuclei (SCN) of mammals, orchestrates an orderly "internal day" of physiology and behavior. The developing biological clock begins to respond to light at an early stage and a particular concern in humans is whether light exposure has disruptive effects on the developing biological clock of infants exposed to constant lighting conditions in neonatal intensive care units (NICUs). Worldwide, eighteen million, or 14%, of newborns estimated to be of low birth weight, are exposed to artificial lighting environments in hospital nurseries annually. Here, we have tested whether constant light (LL) exposure disrupts the developing biological clock of mice, using a circadian reporter transgenic mouse model in which the organization of the central biological clock can be assayed by real-time gene expression imaging. We now find that LL has both acute and long-term disruptive effects on developing biological clocks and that cyclic lighting conditions are critical for developing circadian clocks to coordinate their molecular circadian mechanisms. This suggests that, from the perspective of developing circadian organization in humans, cyclic light conditions in NICUs are likely to be most appropriate for infants.

Animals↗

PubMed2006

Daily rhythmicity of large-conductance Ca2+ -activated K+ currents in suprachiasmatic nucleus neurons.

Neurons within the suprachiasmatic nucleus (SCN) comprise the master circadian pacemaker in mammals. These neurons exhibit circadian rhythms in spontaneous action potential frequency and in the transcription of core circadian clock genes, including Period1 (Per1). Targeted electrophysiological recordings from SCN neurons marked with a green fluorescent protein (GFP) reporter of Per1 gene transcription have previously indicated that K(+) currents are critically involved in the expression of neurophysiological rhythmicity. The present study examined the role of large conductance, Ca(2+)-activated K(+) channels (BK) in the daily rhythmicity of mouse SCN neurons. BK-mediated currents were examined in Per1::GFP neurons under voltage clamp using iberiotoxin, a specific BK channel blocker. BK current was a greater proportion of whole-cell outward currents during the night than during the day. Analysis of iberiotoxin difference currents also demonstrated that BK current amplitude and density were greater during the night and that the day/night difference in steady state amplitude was not due to altered inactivation. Single cell RT-PCR demonstrated the presence of the BK channel transcript, KCNMA1, in Per1-expressing neurons. In situ hybridization analysis further showed that KCNMA1 mRNA was rhythmically expressed in the SCN under light:dark (LD) conditions, peaking during the middle of the night phase. Acute inhibition of BK currents blunted the circadian rhythm SCN neuron spike frequency. These results establish that BK channel function is elevated at night, thus altering SCN neuron activity.

Action Potentials↗

PubMed2005

Constant light desynchronizes mammalian clock neurons.

Circadian organization can be disrupted by constant light, resulting in behavioral arrhythmicity or 'splitting' of rhythms of activity and rest. By imaging molecular rhythms of individual clock neurons in explanted mouse clock nuclei, we now find that constant light desynchronizes clock neurons but does not compromise their ability to generate circadian rhythms. Cellular synchrony within clock nuclei is disrupted during arrhythmicity, whereas neurons in the left and right clock nuclei cycle in antiphase during 'splitting.'

Animals↗

PubMed2004

Characterization of genetically labeled catecholamine neurons in the mouse retina.

Mouse neurons were labeled transgenically with red fluorescent protein (RFP) driven by the tyrosine hydroxylase (TH) promoter and observed in living retinas and brain slices. Two types of retinal amacrine cells expressed TH::RFP. One type had large cell bodies, processes that ramified in S1 of the inner plaxiform layer (IPL) and were TH immunoreactive, identifying them as dopaminergic neurons. A second type had smaller somas, ramified in S3 and lacked TH. Dopaminergic cells had large dendritic fields and exceptionally long axon-like processes, whereas type 2 cells were more compact. Neither cell type exhibited tracer coupling. Thus, murine retinal dopaminergic neurons exhibit functional anatomy similar to their primate counterparts and TH::RFP mice are useful for in situ characterization of catecholaminergic neurons.

Animals↗

PubMed2003

Periodic absence of nursing mothers phase-shifts circadian rhythms of clock genes in the suprachiasmatic nucleus of rat pups.

Effects of absence of nursing mothers on the circadian pacemaker of their offspring were examined by measuring clock genes, the rat Per1 (rPer1) and rPer2 expression rhythms in the pup suprachiasmatic nuclei (SCN). Neonate rats born to mothers kept under a 12-h light : 12-h dark cycle (LD) were blinded immediately after birth and exposed to periodic maternal deprivation where pups were deprived of their mothers during the light phase of 12-h for the first week of life. At postnatal day 6, the periodic maternal deprivation completely phase-reversed the circadian rhythms in expression of the clock genes in the pup SCN and in spontaneous locomotor activity after the pups were weaned at postnatal day 21. The periodic maternal absence also altered the patterns of stress-related gene expressions such as corticotropine-releasing hormone, arginine vasopressin, and glucocorticoid receptor in particular brain areas of the mother-deprived pups at P6. These findings indicate that periodic absence of the nursing mother in the first week of life produces a resetting effect on the neonatal circadian clock and induces stress responses in the hypothalamus-pituitary-adrenal axis.

Animals↗

PubMed2002

Effects of nursing mothers on rPer1 and rPer2 circadian expressions in the neonatal rat suprachiasmatic nuclei vary with developmental stage.

The ability of nursing mothers to entrain the circadian pacemaker of rat pups was examined by measuring the rat Per1 (rPer1) and rPer2 expression levels in the suprachiasmatic nuclei (SCN). Newborn rats from mothers under a light-dark cycle (LD) were blinded immediately after birth and reared by foster mothers under either LD (LD blind pups) or reversed light-dark cycle (DL; DL blind pups). At postnatal day (P)6, small but significant phase differences were observed in the circadian gene expression rhythms of the SCN not only between the blind and sighted pups, but also between the two groups of blind pups, indicating the involvement of both free-running and maternal influence in phase-resetting the circadian rhythms of blind pups. However, from P6 to P13 the circadian rhythms of both LD and DL blind pups showed phase delays of similar extent, which suggests that the influence of nursing mothers was lost. From P13 to P20 (the day of weaning), the rPer1 and rPer2 rhythms phase-shifted in a different manner, the rPer2 rhythm being related more closely to the behavioural rhythm than was the rPer1. This finding suggests a differential influence of mothers on the rPer1 and rPer2 rhythms in the third week of life. It is concluded that the ability of nursing mothers to entrain pup circadian oscillation depends on the developmental stage.

Aging↗