Mieko Kurosawa

Stimulation of the nucleus basalis of Meynert increases acetylcholine release in the cerebral cortex in rats

The effect of focal stimulation of the magnocellular nucleus of the basal forebrain (nucleus basalis of Meynert; NBM) on acetylcholine (ACh) release in the cerebral cortex in the parietal lobe was examined in halothane-anesthetized rats. ACh was measured using a microdialysis method. Focal electrical stimulation of the unilateral NBM increased ACh release in the ipsilateral cerebral cortex in stimulus intensity and frequency dependently. Microinjection of L-glutamate (100 nmol) into the unilateral NBM also increased ACh release in the ipsilateral cerebral cortex. The ACh release in the contralateral cerebral cortex was not affected by these unilateral stimulations of the NBM. It was concluded that focal stimulation of the NBM releases ACh from cortical terminals of cholinergic fibers originating in the NBM.

Repeated massage-like stimulation induces long-term effects on nociception: contribution of oxytocinergic mechanisms.

Massage‐like stroking induces acute antinociceptive effects that can be reversed by an oxytocin antagonist, indicating activation of oxytocin on endogenous pain controlling systems. We now demonstrate an increase in hindpaw withdrawal latencies (HWLs), in response to thermal and mechanical stimuli, which was present after six treatments of massage‐like stroking every other day and which continued to increase through the remaining seven treatments. Repeated massage‐like stroking also resulted in increased oxytocin‐like immunoreactivity (oxytocin‐LI) levels in plasma and periaquaductal grey matter (PAG). Furthermore, increases in HWLs were also present after injections of oxytocin into the PAG (0.1, 0.5 and 1.0 nmol). Intra‐PAG oxytocin injection of 1 nmol followed by 1 or 20 nmol of naloxone attenuated the increments in HWL. Also, there was a dose‐dependent attenuation of the oxytocin‐induced antinociceptive effects following intra‐PAG injection of the µ‐opioid antagonist β‐funaltrexamine (β‐FNA) and the κ‐opioid antagonist nor‐binaltorphimine (nor‐BNI) but not the δ‐antagonist naltrindole. The long‐term antinociceptive effects of massage‐like stroking may be attributed, at least partly, to the oxytocinergic system and its interaction with the opioid system, especially the µ‐ and the κ‐receptors in the PAG.

Increase of meningeal blood flow after electrical stimulation of rat dura mater encephali: mediation by calcitonin gene‐related peptide

1 The dura mater encephali of the rat was exposed and the blood flow around branches of the medial meningeal artery was monitored with a laser Doppler flowmeter. Changes in the meningeal blood flow (MBF) following electrical stimulation of the dura mater at a parasagittal site were registered. The effects of human calcitonin gene‐related peptide (h‐αCGRP) and the CGRP antagonist (h‐αCGRP8–37) on the MBF were tested.

Effects of chemical stimulation of paraventricular nucleus on adrenal and renal nerve activity in rats

The effects of stimulation of the hypothalamic paraventricular nucleus (PVN) by L-glutamate on blood pressure and ongoing activities of adrenal and renal sympathetic nerves were examined in anesthetized rats. Microinjection of excitatory amino acid, L-glutamate (100 nmol in 200 nl saline), into the unilateral PVN resulted in an increase in the ipsilateral adrenal nerve activity, while it resulted in decreases in renal nerve activity and arterial blood pressure. After severance of bilateral carotid sinus and vagal nerves, the decreased response of blood pressure to the same stimulus did not change, while the decreased response of renal nerve activity was almost abolished, and the increased response of adrenal nerve activity still remained, though it slightly attenuated. The involvements of baroreceptor afferents and vagal afferents in these responses were discussed.

Ovarian blood flow responses to electro-acupuncture stimulation at different frequencies and intensities in anaesthetized rats

The purpose of the present study was to investigate changes in ovarian blood flow (OBF) in response to electro-acupuncture (EA) stimulation at different frequencies and intensities in anaesthetized rats. Whether the ovarian sympathetic nerves were involved in OBF responses was elucidated by severance of the ovarian sympathetic nerves. In addition, how changes in the systemic circulation affected OBF was evaluated by continuously recording blood pressure. OBF was measured on the surface of the left ovary using laser Doppler flowmeter. Acupuncture needles with a diameter of 0.3 mm were inserted bilaterally into the abdominal and the hindlimb muscles and connected to an electrical stimulator. Two frequencies-2 Hz (low) and 80 Hz (high)-with three different intensities-1.5, 3, and 6 mA-were applied for 35 s. Both low- and high-frequency EA at 1.5 mA and high-frequency EA at 3 mA had no effect on OBF or mean arterial blood pressure (MAP). Low-frequency EA at 3 and 6 mA elicited significant increases in OBF. In contrast, high-frequency EA with an intensity of 6 mA evoked significant decreases in OBF, followed by decreases in MAP. After severance of the ovarian sympathetic nerves, the increases in the OBF responses to low-frequency EA at 3 and 6 mA were totally abolished, and the responses at 6 mA showed a tendency to decrease, probably because of concomitant decreases in MAP. The decreased OBF and MAP responses to high-frequency EA at 6 mA remained after the ovarian sympathectomy, and the difference in the responses before and after ovarian sympathectomy was nonsignificant. In conclusion, the present study showed that low-frequency EA stimulation increases OBF as a reflex response via the ovarian sympathetic nerves, whereas high-frequency EA stimulation decreases OBF as a passive response following systemic circulatory changes.

Effect of electro-acupuncture stimulation of different frequencies and intensities on ovarian blood flow in anaesthetized rats with steroid-induced polycystic ovaries

BackgroundMaintenance of ovarian blood flow (OBF) is suggested to be important for regular ovulation in women with polycystic ovaries (PCO). The purpose of the present study was to investigate whether electro-acupuncture (EA) of different frequencies and intensities can improve the OBF of anaesthetized rat in the animal model of PCO.MethodsPCO was experimentally induced by a single intramuscular (i.m.) injection of estradiol valerate (EV) in rats. Control rats were given i.m. injection of oil. The involvement of the two ovarian sympathetic nerves; superior ovarian nerve (SON) and plexus ovarian nerve (OPN), in OBF responses was elucidated by severance of SON and OPN in both control and PCO rats. How systemic circulatory changes affect OBF was evaluated by continuous recording of the blood pressure. OBF was measured on the surface of the ovary-using laser Doppler flowmetry. Acupuncture needles were inserted bilaterally into the abdominal and hind limb muscles and connected to an electrical stimulator. Two frequencies – 2 Hz (low) and 80 Hz (high) – with three different intensities – 1.5, 3, and 6 mA – were applied for 35 s.ResultsLow-frequency EA at intensities of 3 and 6 mA elicited significant increases in OBF in the Control group compared to baseline. In the PCO group the increases in OBF were significant only when stimulating with low-frequency EA at 6 mA. After severance of the ovarian sympathetic nerves, the increased response of OBF that had been induced by low-frequency EA in both the Control and PCO group was abolished, indicating that the OBF response is mediated via the ovarian sympathetic nerves. High-frequency EA at 6 mA significantly decreased OBF and mean arterial blood pressure (MAP) in the Control group compared to baseline. In the PCO group, the same stimulation produced similar decreases in MAP, but not in OBF.ConclusionLow-frequency EA stimulation with a strong intensity (6 mA) increases OBF in rats with steroid-induced PCO whereas less strong intensity (3 mA) induces similar changes in control rats. Severance of the ovarian sympathetic nerves, abolish this OBF increase in both study groups, which suggests that the responses of OBF to EA are mediated via the ovarian sympathetic nerves.

Extracellular release of acetylcholine, noradrenaline and serotonin increases in the cerebral cortex during walking in conscious rats

The effect of walking on the extracellular release of acetylcholine (ACh), noradrenaline (NA) and serotonin (5-HT) in the parietal lobe of the cerebral cortex was examined in conscious rats using the microdialysis technique. Walking at the speed of 2.3 m/min for 5 min produced significant increases in ACh, NA and 5-HT release in the cerebral cortical extracellular space. The increase in ACh release was the most prominent among the transmitters examined. It is suggested that the increased release of ACh in the cerebral cortex may contribute at least partly to the increases in the cerebral cortical blood flow during walking.

Chemical chaperone therapy: clinical effect in murine GM1‐gangliosidosis

Certain low‐molecular‐weight substrate analogs act both as in vitro competitive inhibitors of lysosomal hydrolases and as intracellular enhancers (chemical chaperones) by stabilization of mutant proteins. In this study, we performed oral administration of a chaperone compound N‐octyl‐4‐epi‐β‐valienamine to GM1‐gangliosidosis model mice expressing R201C mutant human β‐galactosidase. A newly developed neurological scoring system was used for clinical assessment. N‐Octyl‐4‐epi‐β‐valienamine was delivered rapidly to the brain, increased β‐galactosidase activity, decreased ganglioside GM1, and prevented neurological deterioration within a few months. No adverse effect was observed during this experiment. N‐Octyl‐4‐epi‐β‐valienamine will be useful for chemical chaperone therapy of human GM1‐gangliosidosis. Ann Neurol 2007

Central Orexin-A stimulates pancreatic exocrine secretion via the vagus.

Introduction Digestive organs are controlled from the central nervous system, and the vagus nerve plays an important role. Orexins are recently purified neuropeptides localized in neurons within the lateral hypothalamus. Aim To examine the effects of centrally injected Orexin-A and B on pancreatic exocrine secretion in conscious rats. Methodology Rats were prepared with cannulae draining bile and pancreatic juice separately. The experiments were conducted without anesthesia on day 4 or 5 after the operation. Results Intracerebroventricular administration of Orexin-A (0.25, 0.5, and 1.0 nmol) significantly increased pancreatic fluid and protein output in a dose-dependent manner. A significant stimulatory effect of Orexin-B was not observed. Pretreatment with the ganglion blocker hexamethonium and with atropine completely abolished the stimulatory effect of central Orexin-A. Central Orexin-A significantly increased pancreatic secretion after pretreatment with omeprazole. Intravenous injection of Orexin-A had no effect. Centrally administered Orexin-A stimulated the vagal efferent nerve in anesthetized rats. Conclusions Centrally administered Orexin-A stimulates pancreatic exocrine secretion through the vagal efferent nerve, and the stimulatory action is independent of gastric acid secretion.

Interleukin-1β sensitizes the response of the gastric vagal afferent to cholecystokinin in rat

Interleukin-1beta (IL-1beta) and cholecystokinin (CCK) are important mediators in the development of anorexic response during disease. The role of IL-1beta and CCK in the peripheral mechanisms of anorexia was studied by recording the mass afferent activity of the gastric vagal nerve in anesthetized rats. The i.v. administration of CCK (1 nmol) increased the activity of the vagal nerve, and this response was raised by 55-72% 2 h after i.v. injection of IL-1beta. It is proposed that IL-1beta-induced anorexia is mediated via the sensitization of type A CCK receptors in the periphery.