The role of nitric oxide in the dorsomedial periaqueductal gray(dmPAG)column in cardiovascular responses in urethane-anesthetized male rats

Background:The dorsomedial periaqueductal gray(dmPAG)is a mesencephalic area and has numerous functions including cardiovascular regulation.Because nitric oxide(NO)is present in the dmPAG,here we investigate,the probable cardiovascular effect of NO in the dmPAG.Methods:Five groups(n=6 for each group)were used as follows:(1)control;(2)L-NAME(N^(G)-nitro-L-arginine methyl ester,a NO synthase inhibitor,90 nmol);(3)Larginine(L-Arg,a precursor for NO,60 nmol);(4)Sodium nitroprusside(SNP,a NO donor,27 nmol);and(5)L-Arg+L-NAME.The cardiovascular parameters were recorded by a Power Lab device after cannulation of the femoral artery.Drugs were injected using a stereotaxic instrument.The changes(Δ)in systolic blood pressure(SBP),mean arterial pressure(MAP),and heart rate(HR)were calculated at different times and compared to the control group.Results:Microinjection of L-NAME significantly increased ΔSBP,ΔMAP,and ΔHR more than saline(from p<0.05 to p<0.001).L-Arg only significantly increased ΔHR(p<0.05).In the L-Arg+L-NAME group,the above parameters also significantly increased(from p<0.01 to p<0.05)but not as significantly as with L-NAME alone.Microinjection of SNP significantly decreased ΔSBP and ΔMAP more than in the control and L-NAME groups(from p<0.01 to p<0.001),but ΔHR did not change significantly.Conclusion:The results indicated that NO in dmPAG has an inhibitory effect on cardiovascular responses in anesthetized rats.

Effects of norepinephrine on dorsomedial hypothalamic nucleus of rat before and after synaptic blockade

Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10-5 mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10-5～4×10-5 mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca2+-high Mg2+ ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.

The change of unit discharges in the dorsomedial nucleus of the hypothalamus and the effect of electroacupuncture on it in trauma rats

The unit discharges in the dorsomedial nucleus of the hypothalamus (DMH) were extracellularly recorded with microelectrodes in trauma models of male Sprague-Dawley rats. The main results were as follows : (1) The total number of spontaneously discharged units in DMH of trauma rats was markedly decreased while the number of pain-sensitive units (nociceptive neurons) did not change obviously. (2) The electroacupuncture (EA)at Zusanli (ST36) and Sanyinjiao (Sp6) decreased the spontaneous and pain-evoked firing (discharge) rate, and shortened the durations of pain-evoked firing of pain-excited units in DMH. It also resulted in increase in spontaneous discharge rate of pain-inhibited units and relief of their inhibition from the peripheral noxious stimulations. These results suggest that the depression of the function of DMH caused by the persistent peripheral noxious stimulation may be one of the mechanisms of hyperalgesia. EA at the points of Zusanli (ST36) and Sanyinjiao (Sp6) can interfere with the conduction of pain signals to DMH in the central nervous system and thereby prevent DMH from being depressed , which may partly account for the central mechanisms of acupuncture-analgesia in chronic pain state.

Central Nervous System Control of Glucose Homeostasis

Hypothalamus and brain stem play important roles in Glucose Homeostasis. There are two types of cells in the hypothalamus: Glucose excited (GE) and Glucose inhibited (GI). GE increases glucose concentration and GI decreases glucose concentration. They are located in ventromedial (VMH), arcuate, lateral, dorsomedial and paraventricular areas of hypothalamus. Nucleus of solitary tract, area postrema, dorsomedial nucleus of vagus and basolateral medulla are also related to glucose homeostasis. VMH contains sympathetic nucleus and upregulates plasma glucose and decreases hepatic glycogen, while lateral hypothalamus contains parasympathetic and down regulates plasma glucose. Through Glut-1, dependent transport glucose enters neurons and astrocytes. Glucose is metabolized and provides energy for GE and GI neurons. Their activity is guided by blood sugar level. Blood sugar level sends numerous signals through vagal pathway from periphery. Neuron astrocyte establishes via autonomic system connections with liver, pancreas, adrenal gland and maintains glucose homeostasis. Post prandial glucose levels are regulated by CNS.

Impaired function of the suprachiasmatic nucleus rescues the loss of body temperature homeostasis caused by time-restricted feeding

The suprachiasmatic nucleus(SCN)is the master circadian pacemaker that drives body temperature rhythm.Time-restricted feeding(TRF)has potential as a preventative or therapeutic approach against many diseases.The potential side effects of TRF remain unknown.Here we show that daily 4-h TRF treatment in mice can severely impair body temperature homeostasis and can result in lethality.Nearly half of the mice died at 21℃,and all mice died at 18℃during 4-h TRF.This effect was modulated by the circadian clock and was associated with severe hypothermia due to loss of body temperature homeostasis.Remarkably,disrupting the circadian clock by SCN lesions or constant light rescued lethality during TRF.Analysis of circadian gene expression in the dorsomedial hypothalamus(DMH)demonstrated that TRF reprograms rhythmic transcriptome in DMH and suppresses expression of genes,such as Ccr5 and Calcrl,which are involved in thermoregulation.Together,our results demonstrated a potent effect of TRF on body temperature homeostasis and the role of SCN function in this process.Our results further suggested that circadian arrhythmicity can have potential beneficial effects under certain stress conditions.