Hypoglossal Nucleus Research Articles

Telovelar approach for choroid plexus papilloma in the foramen of Luschka: A safe way using a neuromonitor

BackgroundTumors located in the 4th ventricle are always challenging to neurosurgeons, especially tumors that extend to the cerebellopontine (CP) angle by the foramen of Luschka. Recent advances in microsurgical technique, including the neuromonitor and brainstem mapping, facilitate the surgical resection of tumors located in the foramen of Luschka. Herein, we present the use of the telovelar approach to access a choroid plexus papilloma within the right foramen of Luschka. Case presentationA 28-year-old female presented with a history of sudden onset pulsatile headache and syncope twice without prodrome. The brain MRI revealed a 4th ventricular tumor deviated to the right foramen of Luschka and extending to the CP angle, 2.2cm in diameter. There was no secondary hydrocephalus due to the patent foramen of Magendie and left foramen of Luschka. The patient underwent suboccipital craniotomy and C1 laminectomy with a telovelar approach. The right tonsil was elevated and teal chloride was incised from the foramen of Magendie to the telovelar junction. The tumor was centrally decompressed, and the margin was gently dissected from the brainstem and cerebellum peduncles. Functions of the facial, cochlear, glossopharyngeal, vagus, and hypoglossal nerves and nuclei were monitored. Mapping of the facial nucleus, ambiguous nucleus, and hypoglossal nucleus was also done. Total tumor removal was achieved and the histology showed choroid plexus papilloma. No functional neurological disorientation was observed after surgery. ConclusionThe report demonstrated a safe and effective surgical approach to the foramen of Luschka. The approach yielded a better view of the foramen of Luschka laterally, and up to the middle cerebellar peduncle superiorly. Also, it minimized neural damage, and preserved the function of the cranial nerves and nucleus.

Nitric oxide activates hypoglossal motoneurons by cGMP-dependent inhibition of TASK channels and cGMP-independent activation of HCN channels

Nitric oxide (NO) is an important signaling molecule that regulates numerous physiological processes, including activity of respiratory motoneurons. However, molecular mechanism(s) underlying NO modulation of motoneurons remain obscure. Here, we used a combination of in vivo and in vitro recording techniques to examine NO modulation of motoneurons in the hypoglossal motor nucleus (HMN). Microperfusion of diethylamine (DEA; an NO donor) into the HMN of anesthetized adult rats increased genioglossus muscle activity. In the brain slice, whole cell current-clamp recordings from hypoglossal motoneurons showed that exposure to DEA depolarized membrane potential and increased responsiveness to depolarizing current injections. Under voltage-clamp conditions, we found that NO inhibited a Ba(2+)-sensitive background K(+) conductance and activated a Cs(+)-sensitive hyperpolarization-activated inward current (I(h)). When I(h) was blocked with Cs(+) or ZD-7288, the NO-sensitive K(+) conductance exhibited properties similar to TWIK-related acid-sensitive K(+) (TASK) channels, i.e., voltage independent, resistant to tetraethylammonium and 4-aminopyridine but inhibited by methanandamide. The soluble guanylyl cyclase blocker 1H-(1,2,4)oxadiazole(4,3-a)quinoxaline-1-one (ODQ) and the PKG blocker KT-5823 both decreased NO modulation of this TASK-like conductance. To characterize modulation of I(h) in relative isolation, we tested effects of NO in the presence of Ba(2+) to block TASK channels. Under these conditions, NO activated both the instantaneous (I(inst)) and time-dependent (I(ss)) components of I(h). Interestingly, at more hyperpolarized potentials NO preferentially increased I(inst). The effects of NO on I(h) were retained in the presence of ODQ and blocked by the cysteine-specific oxidant N-ethylmaleimide. These results suggest that NO activates hypoglossal motoneurons by cGMP-dependent inhibition of a TASK-like current and S-nitrosylation-dependent activation of I(h).

Cortical entrainment of human hypoglossal motor unit activities

Output from the primary motor cortex contains oscillations that can have frequency-specific effects on the firing of motoneurons (MNs). Whereas much is known about the effects of oscillatory cortical drive on the output of spinal MN pools, considerably less is known about the effects on cranial motor nuclei, which govern speech/oromotor control. Here, we investigated cortical input to one such motor pool, the hypoglossal motor nucleus (HMN), which controls muscles of the tongue. We recorded intramuscular genioglossus electromyogram (EMG) and scalp EEG from healthy adult subjects performing a tongue protrusion task. Cortical entrainment of HMN population activity was assessed by measuring coherence between EEG and multiunit EMG activity. In addition, cortical entrainment of individual MN firing activity was assessed by measuring phase locking between single motor unit (SMU) action potentials and EEG oscillations. We found that cortical entrainment of multiunit activity was detectable within the 15- to 40-Hz frequency range but was inconsistent across recordings. By comparison, cortical entrainment of SMU spike timing was reliable within the same frequency range. Furthermore, this effect was found to be intermittent over time. Our study represents an important step in understanding corticomuscular synchronization in the context of human oromotor control and is the first study to document SMU entrainment by cortical oscillations in vivo.

Immunocytochemical localization of TASK-3 channels in rat motor neurons.

Motor neurons are large cholinergic neurons located in the brain stem and spinal cord. In recent years, a functional role for TASK channels in cellular excitability and vulnerability to anesthetics of motor neurons has been described. Using a polyclonal monospecific antibody against the tandem pore domain K(+) channel (K2P channel) TWIK-related acid-sensitive K(+) channel (TASK-3), we analyzed the expression of the TASK-3 protein in motor systems of the rat CNS. Immunocytochemical staining showed strong TASK-3 expression in motor neurons of the facial, trigeminal, ambiguus, and hypoglossal nuclei. Oculomotor nuclei (including trochlear and abducens nucleus) were also strongly positive for TASK-3. The parasympathetic Edinger-Westphal nucleus and dorsal vagal nucleus showed significant, but weaker expression compared with somato- and branchiomotoric neurons. In addition, motor neurons in the anterior horn of the spinal cord were also strongly labeled for TASK-3 immunoreactivity. Based on morphological criteria, TASK-3 was found in the somatodendritic compartment of motor neurons. Cellular staining using methyl green and immunofluorescence double-labeling with anti-vesicular acetylcholine transporter (anti-vAChT) indicated ubiquitous TASK-3 expression in motor neurons, whereas in other brain regions TASK-3 showed a widespread but not ubiquitous expression. In situ hybridization using a TASK-3 specific riboprobe verified the expression of TASK-3 in motor neurons at the mRNA level.

Effect of chronic intermittent hypoxia on noradrenergic activation of hypoglossal motoneurons.

In obstructive sleep apnea patients, elevated activity of the lingual muscles during wakefulness protects the upper airway against occlusions. A possibly related form of respiratory neuroplasticity is present in rats exposed to acute and chronic intermittent hypoxia (CIH). Since rats exposed to CIH have increased density of noradrenergic terminals and increased α(1)-adrenoceptor immunoreactivity in the hypoglossal (XII) nucleus, we investigated whether these anatomic indexes of increased noradrenergic innervation translate to increased sensitivity of XII motoneurons to noradrenergic activation. Adult male Sprague-Dawley rats were subjected to CIH for 35 days, with O(2) level varying between 24% and 7% with 180-s period for 10 h/day. They were then anesthetized, vagotomized, paralyzed, and artificially ventilated. The dorsal medulla was exposed, and phenylephrine (2 mM, 10 nl) and then the α(1)-adrenoceptor antagonist prazosin (0.2 mM, 3 × 40 nl) were microinjected into the XII nucleus while XII nerve activity (XIIa) was recorded. The area under integrated XIIa was measured before and at different times after microinjections. The excitatory effect of phenylephrine on XII motoneurons was similar in sham- and CIH-treated rats. In contrast, spontaneous XIIa was more profoundly reduced following prazosin injections in CIH- than sham-treated rats [to 21 ± 7% (SE) vs. 40 ± 8% of baseline, P < 0.05] without significant changes in central respiratory rate, arterial blood pressure, or heart rate. Thus, consistent with increased neuroanatomic measures of noradrenergic innervation of XII motoneurons following exposure to CIH, prazosin injections revealed a stronger endogenous noradrenergic excitatory drive to XII motoneurons in CIH- than sham-treated anesthetized rats.

Rats subjected to chronic-intermittent hypoxia have increased density of noradrenergic terminals in the trigeminal sensory and motor nuclei

Rodents subjected to chronic intermittent hypoxia (CIH) are used to investigate the mechanisms underlying the consequences of the obstructive sleep apnea (OSA) syndrome. Following CIH, rats have an increased density of noradrenergic terminals in the hypoglossal motor nucleus which innervates lingual muscles that protect the upper airway from collapse in OSA patients. Here, we investigated whether such an increase also occurs in other brainstem nuclei. Six pairs of male Sprague-Dawley rats were exposed to CIH or sham treatment for 10h/day for 35 days, with O2 level oscillating between 24% and 7% every 3min. Brainstem sections were immunohistochemically processed for dopamine-β-hydroxylase, a marker for norepinephrine. Noradrenergic terminal varicosities were counted in the center of the trigeminal motor nucleus (Mo5) and the interpolar part of the spinal trigeminal sensory nucleus (Sp5). In the Mo5, noradrenergic varicosities tended to be 9% more numerous in CIH- than sham-treated rats, and in the Sp5 they were 18% more numerous in CIH rats (184±9 vs. 156±8 per 100×100μm counting box; p=0.03, n=18 section pairs).These data suggest that CIH elicits sprouting of noradrenergic terminals in multiple motor and sensory regions of the lower brainstem. This may alter motor and cardiorespiratory outputs and the transmission of cardiorespiratory and motor reflexes in CIH rats and, by implication, in OSA patients.

Infrared heat treatment reduces food intake and modifies expressions of TRPV3-POMC in the dorsal medulla of obesity prone rats

Purpose: Infrared heat, a transient receptor potential vanilloid type-3 (TRPV3) sensitive stimulus, may have potential physiological effects beneficial to treating metabolic syndrome.Materials and methods: Obesity prone (OP) and obesity resistant (OR) rats were fed for seven days on a high-fat diet. Heat treated OP rats were exposed twice daily to infrared light for 20 min each, separated by 80 min of rest. Food intake, blood pressure, blood glucose, and body weight measurements were taken daily and compared between treated OP rats, untreated OP rats, and OR controls. The animals were perfused with 4% paraformaldehyde, and immunohistochemistry was performed on the coronal brainstem sections with polyclonal antibodies against TRPV3 and pro-opiomelanocortin (POMC). The positive-staining cells in the medulla nuclei were quantified using a microscope with reticule grid.Results: Food intake, body weight, and mean arterial blood pressure (MAP) were higher in OP rats, a diet-induced metabolic syndrome model, accompanied by a reduced expression of POMC, an anorectic agent, in the hypoglossal nucleus (HN) and medial nucleus tractus solitarius (mNTS). Food intake in heat-treated OP rats was significantly decreased. POMC positive neuron count was increased in the HN and mNTS of OP rats following treatment. TRPV3 positive staining neurons were increased in the HN and mNTS of OP control rats and decreased following the heat treatments.Conclusion: Lowered POMC and heightened TRPV3 expressions in the HN and mNTS are involved in development of hyperphagia and obesity in OP rats. Exposure to infrared heat modifies TRPV3 and POMC expression in the brainstem, reducing food intake.

Nociceptive Afferents to the Premotor Neurons That Send Axons Simultaneously to the Facial and Hypoglossal Motoneurons by Means of Axon Collaterals

It is well known that the brainstem premotor neurons of the facial nucleus and hypoglossal nucleus coordinate orofacial nociceptive reflex (ONR) responses. However, whether the brainstem PNs receive the nociceptive projection directly from the caudal spinal trigeminal nucleus is still kept unclear. Our present study focuses on the distribution of premotor neurons in the ONR pathways of rats and the collateral projection of the premotor neurons which are involved in the brainstem local pathways of the orofacial nociceptive reflexes of rat. Retrograde tracer Fluoro-gold (FG) or FG/tetramethylrhodamine-dextran amine (TMR-DA) were injected into the VII or/and XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the caudal spinal trigeminal nucleus (Vc). The tracing studies indicated that FG-labeled neurons receiving BDA-labeled fibers from the Vc were mainly distributed bilaterally in the parvicellular reticular formation (PCRt), dorsal and ventral medullary reticular formation (MdD, MdV), supratrigeminal nucleus (Vsup) and parabrachial nucleus (PBN) with an ipsilateral dominance. Some FG/TMR-DA double-labeled premotor neurons, which were observed bilaterally in the PCRt, MdD, dorsal part of the MdV, peri-motor nucleus regions, contacted with BDA-labeled axonal terminals and expressed c-fos protein-like immunoreactivity which induced by subcutaneous injection of formalin into the lip. After retrograde tracer wheat germ agglutinated horseradish peroxidase (WGA-HRP) was injected into VII or XII and BDA into Vc, electron microscopic study revealed that some BDA-labeled axonal terminals made mainly asymmetric synapses on the dendritic and somatic profiles of WGA-HRP-labeled premotor neurons. These data indicate that some premotor neurons could integrate the orofacial nociceptive input from the Vc and transfer these signals simultaneously to different brainstem motonuclei by axonal collaterals.

Alterations in neuronal survival and glial reactions after axotomy by ceftriaxone and minocycline in the mouse hypoglossal nucleus

Some antibiotics are suggested to exert neuroprotective effects via regulation of glial responses. Attenuation of microglial activation by minocycline prevents neuronal death in a variety of experimental models for neurological diseases, such as cerebral ischemia, Parkinson's and Huntington's disease. Ceftriaxone delays loss of neurons in genetic animal models of amyotrophic lateral sclerosis through upregulation of astrocytic glutamate transporter expression (GLT-1). However, it remains largely unknown whether these antibiotics are able to protect neurons in axotomy models for progressive motor neuron diseases. Recent studies have shown that the axotomized motoneurons of the adult rat can survive, whereas those of the adult mouse undergo neuronal degeneration. We thus examined the possible effects of ceftriaxone and minocycline on neuronal loss and glial reactions in the mouse hypoglossal nucleus after axotomy. The survival rate of lesioned motoneurons at 28 days after axotomy (D28) was significantly improved by ceftriaxone and minocycline treatment. There were no significant differences in the cellular densities of astrocytes between ceftriaxone-treated and saline-treated animals. Ceftriaxone administration increased the expression of GLT-1 in the hypoglossal nucleus, while it suppressed the reactive increase of glial fibrillary acidic protein (GFAP) expression to control level. The cellular densities of microglia at D28 were significantly lower in minocycline-treated mice than in saline-treated mice. The time course analysis showed that immediate increase in microglia at D3 and D7 was not suppressed by minocycline. The present observations show that minocycline and ceftriaxone promote survival of lesioned motoneurons in the mouse hypoglossal nucleus, and also suggest that alterations in glial responses might be involved in neuroprotective actions of antibiotics.

The effect of age and tongue exercise on BDNF and TrkB in the hypoglossal nucleus of rats

Age-associated changes in tongue musculature may contribute to dysphagia. One possible treatment is tongue exercise. Exercise induces synaptic plasticity by increasing neurotrophic factors in spinal cord and limb musculature. However, effects of exercise on neurotrophic factors in the cranial sensorimotor system are unknown. Our purpose was to examine the effects of age and exercise on brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the rat hypoglossal nucleus. Young, middle-aged, and old rats were assigned to exercise or no-exercise control conditions. Exercise animals were trained to perform a tongue press task for 8 weeks. Samples from the hypoglossal nucleus were analyzed for BDNF and TrkB immunoreactivity. Baseline maximum tongue forces were similar in all age groups and increased significantly following exercise. BDNF immunoreactivity did not show a significant decrease with age in control group. However, in the exercise group, BDNF was significantly increased in young animals. TrkB immunoreactivity decreased significantly with age in control group, but did not change with exercise. BDNF and TrkB immunoreactivity levels were positively correlated with exercise in young and middle aged animals, but were negatively or weakly correlated with exercise in old animals and with a lack of exercise in no-exercise controls. Tongue exercise was associated with increased tongue forces in rats at all ages. While increases in BDNF and TrkB levels associated with exercise may play a role in mechanisms contributing to increased tongue forces in young and middle-aged rats, other mechanisms may be involved in increased tongue forces observed in old rats.

A direct neuronal connection between the telencephalic nucleus robustus arcopallialis and the nucleus nervi hypoglossi, pars tracheosyringealis in Bengalese finches ( Lonchura striata var. domestica)

Bird species with vocal learning possess a projection from the telencephalic nucleus to the nucleus nervi hypoglossi, pars tracheosyringealis (XIIts) in the medulla, where a final common pathway that controls the vocal organ, i.e., the synrinx, originates. The anatomical basis of this projection has not been well investigated in one species of songbird, the Bengalese finch ( Lonchura striata var. domestica). The present study used anterograde and retrograde tracing experiments to examine and describe this projection in Bengalese finches. Following iontophoretic injections of biotinylated dextran amine into the telencephalic nucleus robustus arcopallialis (RA), we detected anterograde-labeled terminations in the XIIts. In addition, labeled terminals were seen in other vocal–respiratory-related nuclei, such as the dorsomedial nucleus of the nucleus intercollicularis, nucleus infraolivaris superior, nucleus of the rostral ventrolateral medulla, nucleus parambigualis, nucleus ambiguous, and nucleus retroambigualis. Furthermore, following injections into the XIIts, we detected retrograde-labeled cell bodies scattered throughout the ipsilateral RA. The present results revealed that the direct projections of the RA to the XIIts in male Bengalese finches are similar to those in other songbirds with vocal learning abilities.

Fiber connections of the caudal mesopallium in the pigeon

In the present study, immunohistochemistry combined with retrograde labeling techniques were used to determine if hypoglossal motoneurons (HMNs), retrogradely labeled after cholera toxin B subunit (CTB) injection to the genioglossus muscle in rats, show immunoreactivity for alpha-7 and alpha-4 subunits of nicotinic acetylcholine receptors (nAChRs). CTB-positive HMNs projecting to the genioglossus muscle were consistently labeled throughout the rostrocaudal extent of the hypoglossal nuclei with the greatest labeling at and caudal to area postrema. Alpha-7 subunit immunoreactivity was found in 39.44 ± 5.10% of 870 CTB-labeled motoneurons and the alpha-4 subunit in 51.01 ± 3.71% of 983 CTB-positive neurons. Rostrally, the number of genioglossal motoneurons demonstrating immunoreactivity for the alpha-7 subunit was 45.85 ± 10.04% compared to 34.96 ± 5.11% at and caudal to area postrema (P > 0.1). The number of genioglossal motoneurons that showed immunoreactivity for the alpha-4 subunit was 55.03 ± 4.83% at and caudal to area postrema compared to 42.98 ± 3.90% in rostral areas (P = 0.074). These results demonstrate that nAChR immunoreactivity is present in genioglossal motoneurons and suggest a role for alpha-7 and alpha-4 subunits containing nAChRs in the regulation of upper airway patency.

Postnatal changes of Cl− homeostasis in respiration-related rhythmic activity in mouse hypoglossal nucleus

Postnatal changes of Cl− homeostasis in respiration-related rhythmic activity in mouse hypoglossal nucleus

Quantitative analysis of cholinergic inputs including C-terminals to the rat hypoglossal nucleus

Quantitative analysis of cholinergic inputs including C-terminals to the rat hypoglossal nucleus

Regional expression of P2Y4 receptors in the rat central nervous system

P2Y receptors are G protein-coupled receptors composed of eight known subunits (P2Y(1, 2, 4, 6, 11, 12, 13, 14)), which are involved in different functions in neural tissue. The present study investigates the expression pattern of P2Y(4) receptors in the rat central nervous system (CNS) using immunohistochemistry and in situ hybridization. The specificity of the immunostaining has been verified by preabsorption, Western blot, and combined use of immunohistochemistry and in situ hybridization. Neurons expressing P2Y(4) receptors were distributed widely in the rat CNS. Heavy P2Y(4) receptor immunostaining was observed in the magnocellular neuroendocrine neurons of the hypothalamus, red nucleus, pontine nuclei, mesencephalic trigeminal nucleus, motor trigeminal nucleus, ambiguous nucleus, inferior olive, hypoglossal nucleus, and dorsal motor vagus nucleus. Both neurons and astrocytes express P2Y(4) receptors. P2Y(4) receptor immunostaining signals were mainly confined to cell bodies and dendrites of neurons, suggesting that P2Y(4) receptors are mainly involved in regulating postsynaptic events. In the hypothalamus, all the vasopressin (VP) and oxytocin (OT) neurons and all the orexin A neurons were immunoreactive for P2Y(4) receptors. All the neurons expressing P2Y(4) receptors were found to express N-methyl-D: -aspartate receptor 1 (NR1). These data suggest that purines and pyrimidines might be involved in regulation of the release of the neuropeptides VP, OT, and orexin in the rat hypothalamus via P2Y(4) receptors. Further, the physiological and pathophysiological functions of the neurons may operate through coupling between P2Y(4) receptors and NR1.

Axonal projections of medullary swallowing neurons in guinea pigs

A central pattern generator (CPG) for swallowing in the medulla oblongata generates spatially and temporally coordinated movements of the upper airway and alimentary tract. To reveal the medullary neuronal network of the swallowing CPG, we examined the cytoarchitecture of the swallowing CPG and axonal projections of its individual neurons by extracellular recording and juxtacellular labeling of swallowing-related neurons (SRNs) in the medulla in urethane-anesthetized and paralyzed guinea pigs. Three major types of neuronal discharge patterns were identified during fictive swallowing induced by stimulation of the superior laryngeal nerve: early (burst-like activation during the pharyngeal stage), late (activation after the pharyngeal stage), and inhibited (inhibition during the pharyngeal stage) types. Sixteen neurons were successfully labeled in the nucleus tractus solitarii (NTS) and in the medullary reticular formation (RF). No motoneuron was labeled. The SRNs in the NTS had axons projecting to the NTS, RF, nucleus ambiguus, nucleus hypoglossus, and dorsal motor nucleus of the vagus on the ipsilateral side. Some NTS SRNs projected only within the NTS. The axons of SRNs in the RF projected also to the NTS, RF, motor nuclei on the ipsilateral side, and to the other side RF. These findings show anatomic substrates for the neuronal network of the CPG for swallowing, which consists of complex neuronal connections among SRNs in the NTS, RF, and motor nuclei.

Glutamatergic Kölliker–Fuse nucleus neurons innervate hypoglossal motoneurons whose axons form the medial (protruder) branch of the hypoglossal nerve in the rat

This study was performed to understand the anatomical substrates for Kölliker–Fuse nucleus (KFN) modulation of respiratory-related tongue movement. After application of cholera toxin B subunit (CTb) to the medial branch of the hypoglossal nerve (HGn) and injection of biotinylated dextran amine (BDA) into the KFN ipsilaterally, an overlapping distribution of BDA-labeled axon terminals and CTb-labeled neurons was found in the ventral compartment of the hypoglossal nucleus (HGN) ipsilateral to the application and injection sites. At the electron microscopic level, the BDA-labeled terminals made asymmetrical synaptic contacts predominantly with dendrites of the HGN neurons, some of which were labeled with CTb. Using retrograde tracing combined with in situ hybridization, we demonstrated that almost all the KFN neurons sending their axons to the HGN were positive for vesicular glutamate transporter (VGLUT) 2 mRNA but not glutamic acid decarboxylase 67 mRNA. Using a combination of anterograde and retrograde tracing techniques and immunohistochemistry for VGLUT2, we further demonstrated that the KFN axon terminals with VGLUT2 immunoreactivity established close contact with the HGN motoneurons whose axons constitute the medial branch of the HGn. The present results suggest that glutamatergic KFN fibers may exert excitatory influence upon the HGN motoneurons sending their axons to the medial branch of the HGn for the control of protruder tongue muscles contraction to maintain airway patency during respiration.

(-)-Epigallocatechin gallate attenuates NADPH-d/nNOS expression in motor neurons of rats following peripheral nerve injury

BackgroundOxidative stress and large amounts of nitric oxide (NO) have been implicated in the pathophysiology of neuronal injury and neurodegenerative disease. Recent studies have shown that (-)-epigallocatechin gallate (EGCG), one of the green tea polyphenols, has potent antioxidant effects against free radical-mediated lipid peroxidation in ischemia-induced neuronal damage. The purpose of this study was to examine whether EGCG would attenuate neuronal expression of NADPH-d/nNOS in the motor neurons of the lower brainstem following peripheral nerve crush. Thus, young adult rats were treated with EGCG (10, 25, or 50 mg/kg, i.p.) 30 min prior to crushing their hypoglossal and vagus nerves for 30 seconds (left side, at the cervical level). The treatment (pre-crush doses of EGCG) was continued from day 1 to day 6, and the animals were sacrificed on days 3, 7, 14 and 28. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and neuronal nitric oxide synthase (nNOS) immunohistochemistry were used to assess neuronal NADPH-d/nNOS expression in the hypoglossal nucleus and dorsal motor nucleus of the vagus.ResultsIn rats treated with high dosages of EGCG (25 or 50 mg/kg), NADPH-d/nNOS reactivity and cell death of the motor neurons were significantly decreased.ConclusionsThe present evidence indicated that EGCG can reduce NADPH-d/nNOS reactivity and thus may enhance motor neuron survival time following peripheral nerve injury.

Activities of human genioglossus motor units

Upper airway muscles play an important role in regulating airway lumen and in increasing the ability of the pharynx to remain patent in the face of subatmospheric intraluminal pressures produced during inspiration. Due to the considerable technical challenges associated with recording from muscles of the upper airway, much of the experimental work conducted in human subjects has centered on recording respiratory-related activities of the extrinsic tongue protudor muscle, the genioglossus (GG). The GG is one of eight muscles that invest the human tongue (Abd-El-Malek, 1939). All eight muscles are innervated by the hypoglossal nerve (cranial nerve XII) the cell bodies of which are located in the hypoglossal motor nucleus (HMN) of the caudal medulla. Much of the earlier work on the respiratory-related activity of XII motoneurons was based on recordings obtained from single motor axons dissected from the whole XII nerve or from whole muscle GG EMG recordings. Detailed information regarding respiratory-related GG motor unit activities was lacking until as recently as 2006. This paper examines key findings that have emerged from the last decade of work conducted in human subjects. Wherever appropriate, these results are compared with results obtained from in vitro and in vivo studies conducted in non-human mammals. The review is written with the objective of facilitating some discussion and some new thoughts regarding future research directions. The material is framed around four topics: (a) motor unit type, (b) rate coding and recruitment, (c) motor unit activity patterns, and (d) a compartment based view of pharyngeal airway control.

Loss of ATF2 Function Leads to Cranial Motoneuron Degeneration during Embryonic Mouse Development

The AP-1 family transcription factor ATF2 is essential for development and tissue maintenance in mammals. In particular, ATF2 is highly expressed and activated in the brain and previous studies using mouse knockouts have confirmed its requirement in the cerebellum as well as in vestibular sense organs. Here we present the analysis of the requirement for ATF2 in CNS development in mouse embryos, specifically in the brainstem. We discovered that neuron-specific inactivation of ATF2 leads to significant loss of motoneurons of the hypoglossal, abducens and facial nuclei. While the generation of ATF2 mutant motoneurons appears normal during early development, they undergo caspase-dependent and independent cell death during later embryonic and foetal stages. The loss of these motoneurons correlates with increased levels of stress activated MAP kinases, JNK and p38, as well as aberrant accumulation of phosphorylated neurofilament proteins, NF-H and NF-M, known substrates for these kinases. This, together with other neuropathological phenotypes, including aberrant vacuolisation and lipid accumulation, indicates that deficiency in ATF2 leads to neurodegeneration of subsets of somatic and visceral motoneurons of the brainstem. It also confirms that ATF2 has a critical role in limiting the activities of stress kinases JNK and p38 which are potent inducers of cell death in the CNS.