scholarly journals Loss of the metabolism and sleep regulating neuronal populations expressing orexin and oxytocin in the hypothalamus in amyotrophic lateral sclerosis

2021 ◽  
Author(s):  
Sanaz Gabery ◽  
Rebekah M Ahmed ◽  
Jashelle Caga ◽  
Matthew C Kiernan ◽  
Glenda M Halliday ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neuronal Populations ◽  
Lateral Sclerosis

The densitometric physical fractionator for counting neuronal populations: application to a mouse model of familial amyotrophic lateral sclerosis

2003 ◽  
Vol 129 (1) ◽  
pp. 61-71 ◽  
Author(s):  
Giuseppe Luca Ciavarro ◽  
Novella Calvaresi ◽  
Andrea Botturi ◽  
Caterina Bendotti ◽  
Giuseppe Andreoni ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Neuronal Populations ◽  
Lateral Sclerosis

scholarly journals Cortical interneuron-mediated inhibition delays the onset of amyotrophic lateral sclerosis

Brain ◽  
2020 ◽  
Vol 143 (3) ◽  
pp. 800-810 ◽  
Author(s):  
C Sahara Khademullah ◽  
Afif J Aqrabawi ◽  
Kara M Place ◽  
Zahra Dargaei ◽  
Xinyi Liang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Intracortical Inhibition ◽  
Motor Deficits ◽  
Cortical Interneuron ◽  
Neuronal Populations ◽  
Cortical Hyperexcitability ◽  
Symptom Progression ◽  
Lateral Sclerosis

Abstract Amyotrophic lateral sclerosis is a fatal disease resulting from motor neuron degeneration in the cortex and spinal cord. Cortical hyperexcitability is a hallmark feature of amyotrophic lateral sclerosis and is accompanied by decreased intracortical inhibition. Using electrophysiological patch-clamp recordings, we revealed parvalbumin interneurons to be hypoactive in the late pre-symptomatic SOD1*G93A mouse model of amyotrophic lateral sclerosis. We discovered that using adeno-associated virus-mediated delivery of chemogenetic technology targeted to increase the activity of the interneurons within layer 5 of the primary motor cortex, we were able to rescue intracortical inhibition and reduce pyramidal neuron hyperexcitability. Increasing the activity of interneurons in the layer 5 of the primary motor cortex was effective in delaying the onset of amyotrophic lateral sclerosis-associated motor deficits, slowing symptom progression, preserving neuronal populations, and increasing the lifespan of SOD1*G93A mice. Taken together, this study provides novel insights into the pathogenesis and treatment of amyotrophic lateral sclerosis.

scholarly journals Upper and Lower Motor Neuron Degenerations Are Somatotopically Related and Temporally Ordered in the Sod1 Mouse Model of Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 11 (3) ◽  
pp. 369
Author(s):  
Christine Marques ◽  
Thibaut Burg ◽  
Jelena Scekic-Zahirovic ◽  
Mathieu Fischer ◽  
Caroline Rouaux
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Molecular Mechanisms ◽  
Lumbar Spinal Cord ◽  
Retrograde Labelling ◽  
Neuronal Populations ◽  
Temporal Relationships ◽  
Lumbar Spinal ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease arising from the combined degeneration of upper motor neurons (UMN) in the motor cortex, and lower motor neurons (LMN) in the brainstem and spinal cord. This dual impairment raises two major questions: (i) are the degenerations of these two neuronal populations somatotopically related? and if yes (ii), where does neurodegeneration start? If studies carried out on ALS patients clearly demonstrated the somatotopic relationship between UMN and LMN degenerations, their temporal relationship remained an unanswered question. In the present study, we took advantage of the well-described Sod1G86R model of ALS to interrogate the somatotopic and temporal relationships between UMN and LMN degenerations in ALS. Using retrograde labelling from the cervical or lumbar spinal cord of Sod1G86R mice and controls to identify UMN, along with electrophysiology and histology to assess LMN degeneration, we applied rigorous sampling, counting, and statistical analyses, and show that UMN and LMN degenerations are somatotopically related and that UMN depletion precedes LMN degeneration. Together, the data indicate that UMN degeneration is a particularly early and thus relevant event in ALS, in accordance with a possible cortical origin of the disease, and emphasize the need to further elucidate the molecular mechanisms behind UMN degeneration, towards new therapeutic avenues.

Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 63 (1) ◽  
pp. 59-73 ◽  
Author(s):  
Panying Rong
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Acoustic Analysis ◽  
Speaking Rate ◽  
Disease Stage ◽  
Healthy Controls ◽  
Tongue Movement ◽  
Major Barrier ◽  
Syllable Repetition ◽  
Oral Diadochokinesis ◽  
Lateral Sclerosis

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.

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