Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice.

Cholinergic activation can enhance glutamatergic activity in the hippocampus under pathologic conditions, such as Alzheimer's disease. The aim of the present study was to elucidate the relationship between glutamatergic neural functional decline and cholinergic neural dysfunction in the hippocampus. We report the importance of hippocampal cholinergic neurostimulating peptide (HCNP) in inducing acetylcholine synthesis in the medial septal nucleus.

Modulation of excitatory synaptic transmissions by TRPV1 in the spinal trigeminal subnucleus caudalis neurons of neuropathic pain rats.

The present study examined contribution of the transient receptor potential vanilloid 1 channel (TRPV1) to the chronic orofacial pain. Bilateral partial nerve ligation (PNL) of the mental nerve, a branch of trigeminal nerve, was performed to induce neuropathic pain. The withdrawal threshold in response to mechanical stimulation of the lower lip skin was substantially reduced after the surgery in the PNL rats while it remained unchanged in the sham rats.

Effects of progesterone on hypoxia-induced inhibition of excitatory synaptic transmission in the rat nucleus tractus solitarius.

The present study evaluated the ability of progesterone to alleviate the synaptic transmission disturbed by hypoxia in the nucleus tractus solitarius (NTS). Hypoxia with N inhibited spontaneous and tractus solitarius-evoked excitatory postsynaptic currents (sEPSCs and eEPSCs) in NTS neurons of the rat brainstem slice. An additional application of progesterone counteracted the hypoxia-induced inhibition of sEPSCs and eEPSCs without affecting the baseline currents.

Involvement of presynaptic TRPV1 channels in prostaglandin E-induced facilitation of spontaneous synaptic transmission in the rat spinal trigeminal subnucleus caudalis.

Prostaglandin E (PGE) synthesized in the central nervous system influences various physiological functions including nociception. Recently, we have demonstrated that PGE facilitates spontaneous synaptic transmission through presynaptic EP1 receptors in the spinal trigeminal subnucleus caudalis (Vc) neurons that receive nociceptive signals from the orofacial area. Increasing evidence suggests that the action of PGE is related to activation of transient receptor potential vanilloid 1 (TRPV1) channels.

Involvement of the cAMP-Dependent Pathway in Dextromethorphan-Induced Inhibition of Spontaneous Glutamate Transmission in the Nucleus Tractus Solitarius Neurons of Guinea Pigs.

Dextromethorphan (DEX) presynaptically decreases glutamatergic transmission in second-order neurons of the nucleus tractus solitarius (TS). To clarify the inhibitory mechanism of DEX, the present study examined the interaction of DEX with cAMP. The effects of DEX on miniature and TS-evoked excitatory postsynaptic currents (mEPSCs and eEPSCs) were recorded under activation of the cAMP-dependent pathway using the brainstem slices.

Hippocampal Cholinergic Neurostimulating Peptide as a Possible Modulating Factor against Glutamatergic Neuronal Disability by Amyloid Oligomers.

Despite having pathological changes in the brain associated with Alzheimer's disease (AD), some patients have preserved cognitive function. A recent epidemiological study has shown that diet, exercise, cognitive training, and vascular risk monitoring interventions may reduce cognitive decline in at-risk elderly people in the general population. However, the details of molecular mechanisms underlying this cognitive function preservation are still unknown.

Reversal of morphine-induced respiratory depression by doxapram in anesthetized rats.

The present study was undertaken to investigate whether doxapram, a blocker of tandem pore K(+) (TASK-1/-3) channels, is a useful tool for recovery from morphine-induced ventilatory disturbances. Spontaneous ventilation and the hind leg withdrawal response against noxious thermal stimulation were recorded simultaneously in anesthetized rats. Morphine (1.

Mechanisms of pentazocine-induced ventilatory depression and antinociception in anesthetized rats.

This study was performed to clarify mechanisms underlying pentazocine-induced ventilatory depression and antinociception. Spontaneous ventilation and hind leg withdrawal response against nociceptive thermal stimulation were simultaneously recorded in anesthetized rats. Pentazocine decreased minute volume resulting from depression of the ventilatory rate and tracheal airflow, and prolonged the latency of withdrawal response.

Effects of prostaglandin E2 on synaptic transmission in the rat spinal trigeminal subnucleus caudalis.

The spinal trigeminal subnucleus caudalis (Vc) receives preferentially nociceptive afferent signals from the orofacial area. Nociceptive stimuli to the orofacial area induce cyclooxygenase both peripherally and centrally, which can synthesize a major prostanoid prostaglandin E2 (PGE2) that implicates in diverse physiological functions. To clarify the roles of centrally-synthesized PGE2 in nociception, effects of exogenous PGE2 on synaptic transmission in the Vc neurons were investigated in the rat brainstem slice.

Blockade of phosphodiesterase 4 reverses morphine-induced ventilatory disturbance without loss of analgesia.

Aims: Ventilatory disturbance is a fatal side-effect of opioid analgesics. Separation of analgesia from ventilatory depression is important for therapeutic use of opioids. It has been suggested that opioid-induced ventilatory depression results from a decrease in adenosine 3',5'-cyclic monophosphate content in the respiratory-related neurons.

Modulation of glutamatergic transmission by presynaptic N-methyl-D-aspartate mechanisms in second-order neurons of the rat nucleus tractus solitarius.

The present study investigated the physiological function of presynaptic N-methyl-d aspartate (NMDA) mechanisms in glutamatergic transmission in the rat nucleus tractus solitarius (NTS). Membrane currents were recorded from the NTS second-order neurons by using whole-cell patch pipettes including MK-801 to block postsynaptic NMDA receptors. All experiments were performed under blockade of inhibitory synaptic transmission.

The NADPH oxidase inhibitor diphenyleneiodonium activates the human TRPA1 nociceptor.

Transient receptor potential ankyrin 1 (TRPA1) is a Ca(2+)-permeable nonselective cation channel expressed in neuronal and nonneuronal cells and plays an important role in acute and inflammatory pain. Here, we show that an NADPH oxidase (NOX) inhibitor, diphenyleneiodonium (DPI), functions as a TRPA1 activator in human embryonic kidney cells expressing human TRPA1 (HEK-TRPA1) and in human fibroblast-like synoviocytes. Application of DPI at 0.

Pharmacological strategy for overcoming opioid-induced ventilatory disturbances.

Opioids are among the most frequently used analgesics for treatment of severe pain. However, certain of their side-effects, particularly ventilatory disturbances, often restrict their use. Separation of analgesia from respiratory depression has long been a goal in the basic research and therapeutic use of opioids.

A model of the central regulatory system for cough reflex.

Cough is an important defensive reflex that eliminates particles and secretions from the airways and protects the lower airways from the aspiration of foreign materials. Although the classical cough center is thought to be situated in or around the nucleus tractus solitarius (NTS) of the brainstem, our understanding of its profile is still incomplete. Accumulating evidence suggests a new concept of the central regulatory system for cough reflex.

Effects of cholinesterase inhibitors and serotonin-1A receptor agonists on morphine-induced ventilatory depression and antinociception in rats.

Ventilatory depression is a serious side-effect of opioid analgesics. Naloxone, an antagonist of opioid receptors, eliminates not only ventilatory depression but also analgesic effect of opioids. Pharmacological dissociation of adverse reactions from the main action is important clinically and basically.

High doses of oseltamivir phosphate induce acute respiratory arrest in anaesthetized rats.

It has been reported that one of the serious adverse events after the treatment of oseltamivir phosphate (OP) for influenza patients is sudden death resulting from cardiorespiratory arrest. To investigate the aetiology of such an adverse consequence, we examined effects of OP (expressed as free base) on blood pressure and ventilation in anaesthetized rats with vagotomy. Intravenous OP (30-200 mg/kg) caused dose-dependent hypotension and bradycardia in spontaneously breathing animals.

Distinct modulatory effects of 5-HT on excitatory synaptic transmissions in the nucleus tractus solitarius of the rat.

The second-order relay neurons in the nucleus tractus solitarius (NTS) receive numerous peripheral afferent inputs mainly from the vagus nerve. Their activity is modified by several neuromodulators and hence autonomic responses are properly regulated. Serotonin (5-HT) is an important candidate for such neuromodulators, since serotonergic inputs and distribution of 5-HT receptors are provided in the NTS.

M3-receptor activation counteracts opioid-mediated apneusis, but the apneusis per se is not necessarily related to an impaired M3 mechanism in rats.

Aims: Morphine slows the respiratory cycle due to a predominant prolongation of inspiration (apneusis) by postponing the spontaneous termination of inspiration (inspiratory off-switching). The present study investigates whether the morphine-induced apneusis results from impairment of cholinergic mechanisms in the central respiratory network.

Main Methods: The efferent discharge was recorded from the phrenic nerve in artificially ventilated and anesthetized rats with vagotomy.

Dextromethorphan inhibits the glutamatergic synaptic transmission in the nucleus tractus solitarius of guinea pigs.

Dextromethorphan (DEX) is a widely used non-opioid antitussive. However, the precise site of action and its mechanism were not fully understood. We examined the effects of DEX on AMPA receptor-mediated glutamatergic transmission in the nucleus tractus solitarius (NTS) of guinea pigs.

Involvement of platelet-derived growth factor-BB and its receptor-beta in hypoxia-induced depression of excitatory synaptic transmission in the nucleus tractus solitarius of mice.

The role of platelet-derived growth factor (PDGF)-BB / PDGF receptor (PDGFR)-beta signal in inhibition of synaptic transmission by hypoxia is unclear. In the nucleus tractus solitarius neurons, hypoxia with N(2) or NaCN decreased the amplitude of excitatory postsynaptic currents (EPSCs) similarly in wild type (WT) and PDGFR-beta gene-knockout (KO) mice. Recovery of EP SCs after a high concentration of NaCN in KO mice was significantly faster than that in WT mice, while recovery after a low concentration of NaCN or N(2) was not different between both mice.

Hypoxic ventilatory response in platelet-derived growth factor receptor-beta-knockout mice.

The present study investigated whether the platelet-derived growth factor receptor (PDGFR)-beta-mediated mechanisms are involved in the hypoxic ventilatory response through modulating the N-methyl-D-aspartate (NMDA) function. The ventilatory changes during hypoxic challenge (10% O(2), 30 min) were measured plethysmographically in mice selectively lacking the PDGFR-beta in neurons (KO mice) and in control wild-type mice (WT mice) before and after blockade of NMDA receptors. In baseline breathing at rest, respiratory rate, tidal volume, and minute ventilation were similar between WT and KO mice.

Mu-opioid and N-methyl-D-aspartate receptors are localized at laryngeal motoneurons of guinea pigs.

The glottic movement is important for generating efficient airflow in respiration and related reflexes such as coughing. The superior laryngeal nerve (SLN) innervates the cricothyroid muscle and regulates the glottic aperture. A total of 620 laryngeal motoneurons (LMNs) providing efferent fibers to the SLN were retrogradely identified with fluorescent wheat germ agglutinin (WGA) in 8 guinea pigs.

N-methyl-D-aspartate mechanisms in depolarization of augmenting expiratory neurons during the expulsive phase of fictive cough in decerebrate cats.

Cough reflex is characterized by a large expulsive phase for expelling the mucus or particles from the airway. The present study investigated the involvement of N-methyl-D-aspartate (NMDA) mechanisms in the expulsive phase of cough reflex using decerebrate and paralyzed cats. A fictive cough was induced by repetitive stimulation of the superior laryngeal nerve, which was characterized by an increased inspiratory discharge in the phrenic nerve (the stage 1 of fictive cough; SC1) and large spindle-shaped discharge in the iliohypogastric nerve (the stage 2 of fictive cough; SC2).