Differential Loss of Spinal Interneurons in a Mouse Model of ALS

Salamatina, Alina; Yang, Jerry H.; Brenner-Morton, Susan; Bikoff, Jay B.; Fang, Linjing; Kintner, Christopher R.; Jessell, Thomas M.; Sweeney, Lora B.

doi:10.1016/j.neuroscience.2020.08.011

Cited by 27 publications

(44 citation statements)

References 52 publications

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“…A more recent study on the fate of these neurons in the ventral spinal cord of SOD1 G93A mice (173) revealed increased V1 synaptic contacts with motoneuron cell bodies at an early stage of disease, followed by a 50% loss of V1 interneurons at a later stage. Since this loss is delayed compared with motoneurons and V2a excitatory neurons, this also supports the hypothesis that upregulation of inhibition is an early compensatory mechanism, followed by a substantial loss of V1 interneurons later in the disease (173).…”

Section: Recurrent and Cortical Inhibitionsupporting

confidence: 79%

Synaptic Transmission and Motoneuron Excitability Defects in Amyotrophic Lateral Sclerosis

Scamps

Aimond

Hilaire

et al. 2021

Amyotrophic Lateral Sclerosis

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Amyotrophic lateral sclerosis is a fatal adult-onset neurodegenerative disease characterized by progressive muscular weakness and atrophy. The primary feature of amyotrophic lateral sclerosis is the selective loss of motoneurons in the brain and spinal cord. However, changes in synaptic transmission and motoneuron excitability are among the first events that take place during development and accompany the relentless deterioration of motor circuitry. This chapter aims to summarize the current understanding of defects in intrinsic electrophysiological properties of motoneurons, local GABAergic and glycinergic inhibitory as well as cholinergic modulatory interneuron networks, and long-range glutamatergic excitatory input neurons that can precede disease onset or occur during the progression of the disease. We summarize evidence that therapeutic options that target synaptic transmission and intrinsic features of motoneurons might represent novel effective strategies for patients with amyotrophic lateral sclerosis.

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Section: Recurrent and Cortical Inhibitionsupporting

confidence: 79%

Synaptic Transmission and Motoneuron Excitability Defects in Amyotrophic Lateral Sclerosis

Scamps

Aimond

Hilaire

et al. 2021

Amyotrophic Lateral Sclerosis

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“…Previous studies have shown that spinal interneurons are affected in ALS patients and mouse models [ 4 , 17 , 18 , 19 , 20 ]. Therefore, we investigated whether the spinal interneurons are also affected in Matr3 S85C/S85C mice.…”

Section: Resultsmentioning

confidence: 99%

“…However, accumulating studies indicate that other neurons in the CNS are also affected in ALS. Previous studies have found that spinal inhibitory interneurons that control motor neurons are affected in the post-mortem tissue of ALS patients and animal models [ 3 , 4 , 5 ]. In addition, neuropathology was reported in the cortex, hippocampus and cerebellum in ALS patients and animal models [ 2 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Selective Loss of MATR3 in Spinal Interneurons, Upper Motor Neurons and Hippocampal CA1 Neurons in a MATR3 S85C Knock-In Mouse Model of Amyotrophic Lateral Sclerosis

You

Maksimovic

Lee

et al. 2022

Biology

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The neuropathological hallmark of amyotrophic lateral sclerosis (ALS) is motor neuron degeneration in the spinal cord and cortex. Accumulating studies report that other neurons in the central nervous system (CNS) are also affected in ALS. Mutations in Matr3, which encodes a nuclear matrix protein involved in RNA splicing, have been linked to ALS. Previously, we generated a MATR3 S85C knock-in (KI) mouse model that recapitulates early-stage features of ALS. We reported that MATR3 S85C KI mice exhibit defects in lumbar spinal cord motor neurons and in cerebellar Purkinje cells, which are associated with reduced MATR3 immunoreactivity. Here, we show that neurons in various other regions of the CNS are affected in MATR3 S85C KI mice. Using histological analyses, we found selective loss of MATR3 staining in α-motor neurons, but not γ-motor neurons in the cervical and thoracic spinal cord. Loss of MATR3 was also found in parvalbumin-positive interneurons in the cervical, thoracic and lumbar spinal cord. In addition, we found the loss of MATR3 in subsets of upper motor neurons and hippocampal CA1 neurons. Collectively, our findings suggest that these additional neuronal types may contribute to the disease process in MATR3 S85C KI mice.

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“…In addition, a recent study using the SOD G93A mouse model of amyotrophic lateral sclerosis detailed motoneuron innervation by V1 subtypes and demonstrated the susceptibility of these connections to degeneration over time. The work included an elaborate model of progressive upregulation (e.g., compensatory plasticity) in V1 synaptic connectivity before breakdown of interneuronal circuits (Salamatina et al, 2020).…”

Section: Molecular Characterization Of Spins: From Development To Functionmentioning

confidence: 99%

Spinal Interneurons as Gatekeepers to Neuroplasticity after Injury or Disease

et al. 2021

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Spinal interneurons are important facilitators and modulators of motor, sensory, and autonomic functions in the intact CNS. This heterogeneous population of neurons is now widely appreciated to be a key component of plasticity and recovery. This review highlights our current understanding of spinal interneuron heterogeneity, their contribution to control and modulation of motor and sensory functions, and how this role might change after traumatic spinal cord injury. We also offer a perspective for how treatments can optimize the contribution of interneurons to functional improvement.

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Differential Loss of Spinal Interneurons in a Mouse Model of ALS

Cited by 27 publications

References 52 publications

Synaptic Transmission and Motoneuron Excitability Defects in Amyotrophic Lateral Sclerosis

Synaptic Transmission and Motoneuron Excitability Defects in Amyotrophic Lateral Sclerosis

Selective Loss of MATR3 in Spinal Interneurons, Upper Motor Neurons and Hippocampal CA1 Neurons in a MATR3 S85C Knock-In Mouse Model of Amyotrophic Lateral Sclerosis

Spinal Interneurons as Gatekeepers to Neuroplasticity after Injury or Disease

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