Differential expression of the NMDA NR2B receptor subunit in motoneuron populations susceptible and resistant to amyotrophic lateral sclerosis

Fuller, Paula I.; Reddrop, Courtney; Rodger, Jennifer; Bellingham, Mark C.; Phillips, Jacqueline K.

doi:10.1016/j.neulet.2006.01.051

Cited by 18 publications

(9 citation statements)

References 20 publications

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“…These data are generally in line with those from ALS autopsy material [1]. Rat studies showed also that oculomotor MNs (OMNs) and trochlear MNs express much less metabotropic GluR1a glutamate receptors than hypoglossal and spinal MNs [28] and there is a similar difference in the expression of NR2B subunit of the NMDA ionotropic glutamate receptor between the OMNs and hypoglossal MNs [22], which features also reduce possible glutamate toxicity. Notable differences between ALS-vulnerable and ALS-resistant brainstem MNs, supporting a better protection of the latter against such toxicity, exist in the respective patterns of GABA A receptor subunits expression as well [29].…”

Section: Introductionsupporting

confidence: 83%

Sporadic amyotrophic lateral sclerosis: is SMN-Gemins protein complex of importance for the relative resistance of oculomotor nucleus motoneurons to degeneration?

Sulejczak¹,

Chrapusta²,

Dziewulska³

et al. 2018

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Lower motoneurons (MNs) show varied vulnerability in amyotrophic lateral sclerosis (ALS): those of non-ocular brainstem nuclei and most of those of the spinal cord are highly vulnerable, while those of extraocular brainstem nuclei are quite resistant. Results of our former study on the immunoexpression of the survival of motor neuron protein (SMN) and Gemins 2-4 in cervical spinal cord anterior horn α-MNs of sporadic ALS patients suggested that a relative deficit in Gemin2 may play some role in the pathomechanism of the disease. Here, we tested this idea further by comparing immunoexpression patterns of SMN and Gemins 2-8 between MNs of the oculomotor nucleus and α-MNs of the cervical spinal cord anterior horns in autopsy material from sALS patients and controls. In the latter, no considerable difference in any studied protein was found between these structures except that SMN expression was slightly but significantly lower (p < 0.01) in the oculomotor MNs. In the sporadic ALS patients, the expression of SMN, Gemin4 and Gemin7 was significantly weaker (p < 0.05, p < 0.05 and p < 0.01, respectively), while that of Gemin8 was stronger (p < 0.001) in the MNs of the oculomotor nucleus than in the examined cervical spinal cord anterior horn α-MNs. The immunoexpression of Gemin3 and Gemin6 in the spinal cord correlated strongly negatively with ALS duration (Spearman's correlation coefficient: R S =-0.84, p < 0.001, and R S =-0.86, p = 0.002, respectively). In the oculomotor nucleus MNs, no studied protein immunoexpression correlated significantly with ALS duration, but there was a tendency for such negative correlation for Gemin2 (R S =-0.56, p = 0.07). There was an apparent relative deficit of Gemin2 and Gemin8 in the spinal cord α-MNs and of Gemins 2, 4 and 7 in the oculomotor nucleus MNs. These data do not support the hypothesis that the diverse ALS vulnerability of the two MN subsets is related to their disparate expression patterns of SMN and Gemins 2-8. The differences in these patterns may result from ALS-related epiphenomena, or from intrinsic differences in the structure and function between the MN subsets, or both.

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Section: Introductionsupporting

confidence: 83%

Sporadic amyotrophic lateral sclerosis: is SMN-Gemins protein complex of importance for the relative resistance of oculomotor nucleus motoneurons to degeneration?

Sulejczak¹,

Chrapusta²,

Dziewulska³

et al. 2018

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“…Based on inmunohistochemical procedures, neurons that use aspartate and/or glutamate as neurotransmitters have been reported to project towards the oculomotor nucleus from different visuomotor and vestibular brainstem sources (Kevetter & Hoffman, 1991; Carpenter, 1992; Spencer & Wang, 1996; Nguyen & Spencer, 1999; Nguyen et al 1999). In addition, ionotropic and metabotropic glutamate receptors have been identified within the oculomotor nucleus by measuring the expression of different subunits (Laslo et al 2001 a , b ; Fuller et al 2006; Hideyama et al 2010). In abducens motoneurons recorded in vivo , the activation of glutamate receptors does not produce any change in input resistance, and induces a small membrane potential depolarization that does not bring the motoneuron to fire (Durand et al 1987).…”

Section: Introductionmentioning

confidence: 99%

Glutamate modulates the firing rate in oculomotor nucleus motoneurons as a function of the recruitment threshold current

Torres-Torrelo¹,

Rodríguez-Rosell²,

Nuñez-Abades³

et al. 2012

The Journal of Physiology

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Key points• This study deals with the cellular mechanisms involved in firing rate modulation in vivo in the oculomotor system where there are requirements for high firing rates by motoneurons.• The study demonstrates that glutamate effects depend on the recruitment threshold and, presumably, motoneuron size.• Mid-and high-threshold motoneurons in response to glutamate decrease their voltage threshold and strengthened the tonic and phasic components of the firing rate.• In a functional context, motoneurons could be recruited at lower recruitment threshold and could generate a strong muscle contraction under glutamate modulation to perform saccadic eye movements with different velocities and/or to maintain the eye in different eccentric positions in the orbit.• Our results suggest that the recruitment and firing behaviour of ocular motoneurons can be modified in vivo by glutamatergic synaptic inputs. It provides a link between cellular function and behavioural motoneuron output.Abstract Studies in alert preparations have demonstrated that ocular motoneurons exhibit a phasic-tonic firing rate related to eye velocity and position, respectively. The slopes of these relationships are higher in motoneurons with higher recruitment threshold and have been proposed to depend upon synaptic input. To investigate this hypothesis, motoneurons of the rat oculomotor nucleus were recorded in a brain slice preparation in control conditions and during glutamate (5 μM) application to the bath. Glutamate did not affect membrane potential or input resistance, but produced a decrease in rheobase and depolarization voltage as a function of the current needed for generating a maintained repetitive discharge (recruitment threshold current). In addition, glutamate compressed the range of recruitment threshold current (0.1-0.4 nA) as compared to the control (0.15-0.7 nA). Glutamate exposed motoneurons showed an increase in the tonic frequency gain and the peak frequency. Such increments depended on the recruitment threshold current and the last recruited motoneurons almost doubled the tonic frequency gain (35.2 vs. 57.9 spikes s −1 nA −1 ) and the peak frequency (52.4 vs. 102.6 spikes s −1 ). Finally, glutamate increased the spike frequency adaptation due to a significant increase in the phasic firing component as compared to the tonic one. In conclusion, glutamate modulates tonic and phasic discharge properties as a function of the recruitment threshold current and, presumably, motoneuron size. These findings contribute to understand the link between cellular functions and motoneuron discharge during oculomotor behaviour.

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“…Of those, the NR2B subunit is found to increase glutamateevoked Ca 2+ influx into neurons (64). As has been shown recently, the mRNA for this calciumpermeable subunit is expressed higher in hypoglossal motor neurons prone to ALS damage compared to resistant oculomotor ones, while there is no difference in expression of mRNA for the other subunits (65).…”

Section: Introductionmentioning

confidence: 72%

Survey of ALS‐associated factors potentially promoting Ca²⁺overload of motor neurons

Ionov

2007

Amyotrophic Lateral Sclerosis

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The deleterious consequences of Ca(2+) overload are thought to be a probable cause of motoneuronal death in ALS, although the overloading mechanism is currently unclear. In this paper some ALS-linked factors are analysed with regard to their influence on Ca(2+ )influx into neurons. Intensive cortex activity can render motor neurons susceptible to stimulation of calcium-permeable glutamate NMDA-receptors; increase in CSF concentrations of glutamate, glycine, and norepinephrine supposedly can intensify these receptors' activity. Elevated CSF levels of GABA and reduced levels of serotonin can promote Ca(2+ )influx through glutamate AMPA-receptors and voltage-gated channels of L-, N-, and P-type. Additionally, brain ischaemia can contribute to Ca(2+ )overload of motor neurons. Thus, ALS is characterized by the unique combination of factors potentially able to promote the overload of motor neurons with calcium.

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Differential expression of the NMDA NR2B receptor subunit in motoneuron populations susceptible and resistant to amyotrophic lateral sclerosis

Cited by 18 publications

References 20 publications

Sporadic amyotrophic lateral sclerosis: is SMN-Gemins protein complex of importance for the relative resistance of oculomotor nucleus motoneurons to degeneration?

Sporadic amyotrophic lateral sclerosis: is SMN-Gemins protein complex of importance for the relative resistance of oculomotor nucleus motoneurons to degeneration?

Glutamate modulates the firing rate in oculomotor nucleus motoneurons as a function of the recruitment threshold current

Survey of ALS‐associated factors potentially promoting Ca²⁺overload of motor neurons

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Differential expression of the NMDA NR2B receptor subunit in motoneuron populations susceptible and resistant to amyotrophic lateral sclerosis

Cited by 18 publications

References 20 publications

Sporadic amyotrophic lateral sclerosis: is SMN-Gemins protein complex of importance for the relative resistance of oculomotor nucleus motoneurons to degeneration?

Sporadic amyotrophic lateral sclerosis: is SMN-Gemins protein complex of importance for the relative resistance of oculomotor nucleus motoneurons to degeneration?

Glutamate modulates the firing rate in oculomotor nucleus motoneurons as a function of the recruitment threshold current

Survey of ALS‐associated factors potentially promoting Ca2+overload of motor neurons

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Product

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Survey of ALS‐associated factors potentially promoting Ca²⁺overload of motor neurons