ABSTRACT
The term for re-entrainment to a new light-dark cycle in streptozotocin (STZ)-induced diabetic rats was significantly longer than that in control rats. In STZ-induced diabetic rats, the same level of phase delay in the suprachiasmatic nucleus neuronal firing rhythm was observed in control rats after glutamate application. Therefore, 5-HT function in the hypothalamus is thought to be decreased in STZ-induced diabetic rats. These results suggest that postsynaptic neuronal function is still maintained in the suprachiasmatic nucleus of STZ-induced diabetic rats. Therefore, 5-HT mechanisms may play an important role in the maintenance of this function.
Subject(s)
Brain/metabolism , Circadian Rhythm/physiology , Diabetes Mellitus, Experimental/metabolism , Motor Activity/physiology , Suprachiasmatic Nucleus/metabolism , 5-Hydroxytryptophan/metabolism , Animals , Circadian Rhythm/drug effects , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/physiopathology , Glutamic Acid/pharmacology , Hydroxyindoleacetic Acid/metabolism , Male , Rats , Rats, Wistar , Serotonin/metabolism , Streptozocin , Suprachiasmatic Nucleus/drug effects , Suprachiasmatic Nucleus/physiopathologyABSTRACT
The entrainment function in the suprachiasmatic nucleus (SCN) of young non-diabetic Otsuka Long Evans Tokushima Fatty (OLETF) rats was studied. OLETF rats significantly needed more days for re-entrainment to a new light-dark cycle than control Long Evans Tokushima Otsuka (LETO) rats. We also assessed Fos expression in the SCN induced by dim light exposure. The number of Fos-immunoreactive cells was significantly decreased in 5- to 13-week-old OLETF rats compared with LETO rats. Moreover, the effect of glutamate on neuronal activity in the SCN of OLETF rats were investigated. In young non-diabetic OLETF rats, the phase delay in the SCN neuronal firing rhythm induced by 1 microM glutamate was significantly less than that in LETO rats. These results suggested that the entrainment function is reduced in OLETF rats before the onset of diabetes.
Subject(s)
Suprachiasmatic Nucleus/physiology , Animals , Circadian Rhythm , Genes, fos/physiology , Glutamic Acid/pharmacology , Male , Neurons/drug effects , Neurons/physiology , Rats , Rats, Long-EvansABSTRACT
mPer1, a mouse gene, is a homolog of the Drosophila clock gene period and has been shown to be closely associated with the light-induced resetting of a mammalian circadian clock. To investigate whether the rapid induction of mPer1 after light exposure is necessary for light-induced phase shifting, we injected an antisense phosphotioate oligonucleotide (ODN) to mPer1 mRNA into the cerebral ventricle. Light-induced phase delay of locomotor activity at CT16 was significantly inhibited when the mice were pretreated with mPer1 antisense ODN 1 hr before light exposure. mPer1 sense ODN or random ODN treatment had little effect on phase delay induced by light pulses. In addition, glutamate-induced phase delay of suprachiasmatic nucleus (SCN) firing rhythm was attenuated by pretreatment with mPer1 antisense ODN, but not by random ODN. The present results demonstrate that induction of mPer1 mRNA is required for light- or glutamate-induced phase shifting, suggesting that the acute induction of mPer1 mRNA in the SCN after light exposure is involved in light-induced phase shifting of the overt rhythm.
Subject(s)
Circadian Rhythm/physiology , Glutamic Acid/pharmacology , Light , Motor Activity/physiology , Nuclear Proteins/metabolism , Suprachiasmatic Nucleus/physiology , Animals , Brain/metabolism , Cell Cycle Proteins , Electrophysiology , Male , Mice , Mice, Inbred BALB C , Nuclear Proteins/genetics , Oligonucleotides/metabolism , Oligonucleotides, Antisense/pharmacology , Period Circadian Proteins , Periodicity , RNA, Messenger/metabolism , Suprachiasmatic Nucleus/drug effectsABSTRACT
We assessed light-induced Fos-immunoreactive cells in the suprachiasmatic nucleus of diabetic rats. The number of Fos-immunoreactive cells significantly decreased in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats as compared with control Long-Evans Tokushima Otsuka (LETO) rats. In contrast there was no decrease in the number of Fos-immunoreactive cells in young OLETF rats which have not yet developed diabetes. Two months after the administration of streptozotocin (STZ) to Wistar rats, the number of Fos-immunoreactive cells significantly decreased, although 1 week after the administration of STZ, the number had not yet changed in these STZ-induced diabetic rats. These results suggest that chronic diabetic (hyperglycemic) conditions may affect the light entraining responses in the suprachiasmatic nucleus (SCN).
