Healthy and diseased corticospinal motor neurons are selectively transduced upon direct AAV2-2 injection into the motor cortex

Traumatic brain injury (TBI) is a well-established risk factor for several neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, however, a link between TBI and amyotrophic lateral sclerosis (ALS) has not been clearly elucidated. Using the SOD1G93A rat model known to recapitulate the human ALS condition, we found that exposure to mild, repetitive TBI lead ALS rats to experience earlier disease onset and shortened survival relative to their sham counterparts. Importantly, increased severity of early injury symptoms prior to the onset of ALS disease symptoms was linked to poor health of corticospinal motor neurons and predicted worsened outcome later in life. Whereas ALS rats with only mild behavioral injury deficits exhibited no observable changes in corticospinal motor neuron health and did not present with early onset or shortened survival, those with more severe injury-related deficits exhibited alterations in corticospinal motor neuron health and presented with significantly earlier onset and shortened lifespan. While these studies do not imply that TBI causes ALS, we provide experimental evidence that head injury is a risk factor for earlier disease onset in a genetically predisposed ALS population and is associated with poor health of corticospinal motor neurons.

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Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex

Neurología (English Edition) ◽

10.1016/j.nrleng.2017.12.004 ◽

2019 ◽

Author(s):

N.I. Martínez-Torres ◽

D. González-Tapia ◽

M. Flores-Soto ◽

N. Vázquez-Hernández ◽

H. Salgado-Ceballos ◽

...

Keyword(s):

Spinal Cord ◽

Motor Cortex ◽

Motor Neurons

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Probing Changes in Neural Interaction During Adaptation

Neural Computation ◽

10.1162/089976603322362392 ◽

2003 ◽

Vol 15 (10) ◽

pp. 2359-2377 ◽

Cited By ~ 18

Author(s):

Liqiang Zhu ◽

Ying-Cheng Lai ◽

Frank C. Hoppensteadt ◽

Jiping He

Keyword(s):

Motor Cortex ◽

Motor Neurons ◽

Stochastic Models ◽

Primary Motor Cortex ◽

Directed Transfer Function ◽

Neural Interaction ◽

Functional Interactions ◽

External Perturbations ◽

The Neural Network ◽

Before And After

A procedure is developed to probe the changes in the functional interactions among neurons in primary motor cortex of the monkey brain during adaptation. A monkey is trained to learn a new skill, moving its arm to reach a target under the influence of external perturbations. The spike trains of multiple neurons in the primary motor cortex are recorded simultaneously. We utilize the methodology of directed transfer function, derived from a class of linear stochastic models, to quantify the causal interactions between the neurons. We find that the coupling between the motor neurons tends to increase during the adaptation but return to the original level after the adaptation. Furthermore, there is evidence that adaptation tends to affect the topology of the neural network, despite the approximate conservation of the average coupling strength in the network before and after the adaptation.

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MCP1-CCR2 and neuroinflammation in the ALS motor cortex with TDP-43 pathology

Journal of Neuroinflammation ◽

10.1186/s12974-019-1589-y ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 6

Author(s):

Javier H. Jara ◽

Mukesh Gautam ◽

Nuran Kocak ◽

Edward F. Xie ◽

Qinwen Mao ◽

...

Keyword(s):

Motor Cortex ◽

Motor Neuron ◽

Motor Neurons ◽

Neuronal Cells ◽

Treatment Strategies ◽

Brain Parenchyma ◽

Neuroinflammatory Response ◽

Upper Motor Neurons ◽

Als Patients ◽

Betz Cells

Abstract Background The involvement of non-neuronal cells and the cells of innate immunity has been attributed to the initiation and progression of ALS. TDP-43 pathology is observed in a broad spectrum of ALS cases and is one of the most commonly shared pathologies. The potential involvement of the neuroimmune axis in the motor cortex of ALS patients with TDP-43 pathology needs to be revealed. This information is vital for building effective treatment strategies. Methods We investigated the presence of astrogliosis and microgliosis in the motor cortex of ALS patients with TDP-43 pathology. prpTDP-43A315T-UeGFP mice, corticospinal motor neuron (CSMN) reporter line with TDP-43 pathology, are utilized to reveal the timing and extent of neuroimmune interactions and the involvement of non-neuronal cells to neurodegeneration. Electron microscopy and immunolabeling techniques are used to mark and monitor cells of interest. Results We detected both activated astrocytes and microglia, especially rod-like microglia, in the motor cortex of patients and TDP-43 mouse model. Besides, CCR2+ TMEM119- infiltrating monocytes were detected as they penetrate the brain parenchyma. Interestingly, Betz cells, which normally do not express MCP1, were marked with high levels of MCP1 expression when diseased. Conclusions There is an early contribution of a neuroinflammatory response for upper motor neuron (UMN) degeneration with respect to TDP-43 pathology, and MCP1-CCR2 signaling is important for the recognition of diseased upper motor neurons by infiltrating monocytes. The findings are conserved among species and are observed in both ALS and ALS-FTLD patients.

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