Physiological Processes Commons^™

Persistent Stress-Induced Neuroplastic Changes In The Locus Coeruleus/Norepinephrine System, Olga Borodovitsyna, Neal Joshi, Daniel Chandler

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Neural plasticity plays a critical role in mediating short- and long-term brain responses to environmental stimuli. A major effector of plasticity throughout many regions of the brain is stress. Activation of the locus coeruleus (LC) is a critical step in mediating the neuroendocrine and behavioral limbs of the stress response. During stressor exposure, activation of the hypothalamic-pituitary-adrenal axis promotes release of corticotropin-releasing factor in LC, where its signaling promotes a number of physiological and cellular changes. While the acute effects of stress on LC physiology have been described, its long-term effects are less clear. This review will describe how stress …

Validation Of Minimally-Invasive Sample Collection Methods For Measurement Of Telomere Length, Stephanie A. Stout, Jue Lin, Natalie Hernandez, Elyssia Poggi Davis, Judith E. Carroll, Laura M. Glynn

Psychology Faculty Articles and Research

Objective: The discovery of telomere length (TL) as a biomarker of cellular aging and correlate of age-related disease has generated a new field of research in the biology of healthy aging. Although the most common method of sample collection for TL is venous blood draw, less-invasive DNA collection methods are becoming more widely used. However, how TL relates across tissues derived from these sample collection methods is poorly understood. The current study is the first to characterize the associations in TL across three sample collection methods: venous whole blood, finger prick dried blood spot and saliva.

Methods: TL …

A Protocol For The Administration Of Real-Time Fmri Neurofeedback Training, Matthew Sherwood, Emily E. Diller, Elizabeth Ey, Subhashini Ganapathy, Jeremy T. Nelson, Jason G. Parker

Neuroscience, Cell Biology & Physiology Faculty Publications

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can …

The Motor Cortical Representation Of A Muscle Is Not Homogeneous In Brain Connectivity, Jo Armour Smith, Alaa Albishi, Sarine Babikian, Skulpan Asavasopon, Beth E. Fisher, Jason Kutch

Physical Therapy Faculty Articles and Research

Functional connectivity patterns of the motor cortical representational area of single muscles have not been extensively mapped in humans, particularly for the axial musculature. Functional connectivity may provide a neural substrate for adaptation of muscle activity in axial muscles that have both voluntary and postural functions. The purpose of this study was to combine brain stimulation and neuroimaging to both map the cortical representation of the external oblique (EO) in primary motor cortex (M1) and supplementary motor area (SMA), and to establish the resting-state functional connectivity associated with this representation. Motor evoked potentials were elicited from the EO muscle in …

Mixed-Mode Oscillations In Pyramidal Neurons Under Antiepileptic Drug Conditions, Babak V-Ghaffari, M. Kouhnavard, Sherif M. Elbasiouny

Neuroscience, Cell Biology, & Physiology Faculty Publications

Subthreshold oscillations in combination with large-amplitude oscillations generate mixedmode oscillations (MMOs), which mediate various spatial and temporal cognition and memory processes and behavioral motor tasks. Although many studies have shown that canard theory is a reliable method to investigate the properties underlying the MMOs phenomena, the relationship between the results obtained by applying canard theory and conductancebased models of neurons and their electrophysiological mechanisms are still not well understood. The goal of this study was to apply canard theory to the conductance-based model of pyramidal neurons in layer V of the Entorhinal Cortex to investigate the properties of MMOs under …

Regulation Of Trpm7 By Cytosolic Mg2+ And Ph: Insights From Vsp Expression, Pavani Beesetty, Krystyna Blanka Wieczerzak, Tatyana Zhelay, Taku Kaitsuka, Masayuki Matsushita, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

TRPM7 is an ion channel/protein kinase belonging to TRP melastatin and eEF2 kinase families. Under physiological conditions, most native TRPM7 channels are inactive, due to inhibition by cytoplasmic Mg2+, protons and polyamines. ITRPM7 is strongly potentiated when cell cytosol is depleted of Mg2+ or alkalinized. In Jurkat T cells, Mg2+ inhibition involves a high and a low affinity inhibitor sites, whereas proton inhibition involves only one site. Like many other TRP channels, TRPM7 is activated by PI(4,5)P2 and suppressed by its hydrolysis. Here we examined Mg2+ and pH inhibition of native TRPM7 channels in HEK293 cells overexpressing voltage-sensitive phospholipid phosphatase …

Analysis Of Proprioceptive Sensory Innervation Of The Mouse Soleus: A Whole-Mount Muscle Approach, Martha Jean Sonner, Marie C. Walters, David R. Ladle

Neuroscience, Cell Biology & Physiology Faculty Publications

Muscle proprioceptive afferents provide feedback critical for successful execution of motor tasks via specialized mechanoreceptors housed within skeletal muscles: muscle spindles, supplied by group Ia and group II afferents, and Golgi tendon organs, supplied by group Ib afferents. The morphology of these proprioceptors and their associated afferents has been studied extensively in the cat soleus, and to a lesser degree, in the rat; however, quantitative analyses of proprioceptive innervation in the mouse soleus are comparatively limited. The present study employed genetically-encoded fluorescent reporting systems to label and analyze muscle spindles, Golgi tendon organs, and the proprioceptive sensory neuron subpopulations supplying …

Survival And Growth Of C57bl/6j Mice Lacking The Bk Channel, Kcnma1: Lower Adult Body Weight Occurs Together With Higher Body Fat, Susan T. Halm, Michael A. Bottomley, Mohammed M. Almutairi, Mauricio Di Fulvio, Dan R. Halm

Neuroscience, Cell Biology & Physiology Faculty Publications

Big conductance potassium (BK) channels contribute to K⁺ flow and electrical behavior in many cell types. Mice made null for the gene (Kcnma1) producing the BK channel (BK^KO) exhibit numerous deficits in physiological functions. Breeding mice lacking a single allele of Kcnma1 (C57BL/6J background) had litter sizes of approximately eight pups. For the period of maternal care (P0– P21), pup deaths peaked at P1 with a second less severe interval of death peaking near P13. Early deaths were twice as likely during a 20-month period of building construction compared with the quiescent period after cessation of construction. Births …

The Effects Of Exercise Preconditioning On Focal Ischemic Stroke, Gillian Grohs

Theses and Dissertations--Medical Sciences

Cleaved fragments of the extracellular matrix protein perlecan have been shown to promote neuroprotection and repair after ischemic stroke. The cysteine proteases cathepsin B and L as well as the metalloprotease bone morphogenic protein 1 (BMP-1) are capable of releasing the biologically active C-terminal laminin-like globular domain (LG3) of perlecan. Exercise, a known method of reducing stroke risk and severity, has been shown to increase the expression of some proteases associated with perlecan processing. Using a transient distal middle cerebral artery occlusion (MCAo) model for focal ischemic stroke we show that while 7 days of running only slightly decreased infarct …

Neuroinflammation In Alzheimer's Disease And Vascular Cognitive Impairment, Erica M. Weekman

Theses and Dissertations--Physiology

It was once believed that the brain was immunologically privileged with no resident or infiltrating immune cells; however, now it is understood that the cells of the brain are capable of a wide range of inflammatory processes and phenotypes. Inflammation in the brain has been implicated in several disease processes such as Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID); however, the role of inflammation in these two dementias is poorly understood.

When we stimulated a pro-inflammatory phenotype with an adeno-associated viral vector in a transgenic mouse model of AD that develops Aβ plaques, we saw a pro-inflammatory …

The Substrate Of The Biopsychosocial Influences In The Carcinogenesis Of The Digestive Tract, Georgică C. Târtea, Cristina Florescu, Daniel Pirici, Daniel Caragea, Elena A. Târtea, Cristin C. Vere

Journal of Mind and Medical Sciences

Digestive cancer represents a severe public health problem, being one of the main causes of death. It is considered a multifactorial disease, with hereditary predisposition, environmental factors, and other factors involved in carcinogenesis. Both the evolution and the pathogenesis of digestive neoplasms remain incompletely elucidated. As a multifactorial disease, it can be approached by taking into account the biopsychosocial influences via enteric nervous system. Many peptides and non-peptides having a neurotransmitter role can be found in the enteric nervous system, which can influence the neoplastic process directly or indirectly by affecting some angiogenic, growth, and metastasis factors. However, neurotransmitters can …

Reduced Motor Neuron Excitability Is An Important Contributor To Weakness In A Rat Model Of Sepsis, Paul Nardelli, Jacob A. Vincent, Randall K. Powers, Timothy C. Cope, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

The mechanisms by which sepsis triggers intensive care unit acquired weakness (ICUAW) remain unclear. We previously identified difficulty with motor unit recruitment in patients as a novel contributor to ICUAW. To study the mechanism underlying poor recruitment of motor units we used the rat cecal ligation and puncture model of sepsis. We identified striking dysfunction of alpha motor neurons during repetitive firing. Firing was more erratic, and often intermittent. Our data raised the possibility that reduced excitability of motor neurons was a significant contributor to weakness induced by sepsis. In this study we quantified the contribution of reduced motor neuron …

Combining Real-Time Fmri Neurofeedback Training Of The Dlpfc With N-Back Practice Results In Neuroplastic Effects Confined To The Neurofeedback Target Region, Matthew Sherwood, Michael P. Weisend, Jessica H. Kane, Jason G. Parker

Neuroscience, Cell Biology & Physiology Faculty Publications

In traditional fMRI, individuals respond to exogenous stimuli and are naïve to the effects of the stimuli on their neural activity patterns. Changes arising in the fMRI signal are analyzed post-hoc to elucidate the spatial and temporal activation of brain regions associated with the tasks performed. The advent of real-time fMRI has enabled a new method to systematically alter brain activity across space and time using neurofeedback training (NFT), providing a new tool to study internally-driven processes such as neuroplasticity. In this work, we combined n-back practice with fMRI-NFT of the left dorsolateral prefrontal cortex (DLPFC) to better understand the …

Synapse Formation In Monosynaptic Sensory–Motor Connections Is Regulated By Presynaptic Rho Gtpase Cdc42, Fumiyasu Imai, David R. Ladle, Jennifer R. Leslie, Xin Duan, Tilat A. Rizvi, Georgianne M. Ciraolo, Yi Zheng, Yutaka Yoshida

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in monosynaptic …

Mitogenic Activation And Proliferation Of T Lymphocytes In Trpm7 Kinase-Dead Mutant Mice, Pavani Beesetty, Masayuki Matsushita, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

Calcium and magnesium ions have been implicated in T lymphocyte proliferation in response to antigen recognition. Specifically, it is believed that calcium and magnesium elevations in the cytoplasm are necessary for efficient T cell proliferation. Research over the past two decades has focused on identifying the plasma membrane ion channels responsible for governing Ca2+ influx in lymphocytes and Orai-STIM, Kv1.3 and KCa3.1 channels were shown to be crucial for persistent calcium mobilization. Pharmacologic or genetic suppression of calcium influx gives rise to lymphoproliferative defects. In addition to Ca2+, several studies have demonstrated that Mg2+ influx positively regulates proliferation. TRPM7 is …

Reversible Recruitment Of A Homeostatic Reserve Pool Of Synaptic Vesicles Underlies Rapid Homeostatic Plasticity Of Quantal Content, Xueyong Wang, Martin J. Pinter, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Homeostatic regulation is essential for the maintenance of synaptic strength within the physiological range. The current study is the first to demonstrate that both induction and reversal of homeostatic upregulation of synaptic vesicle release can occur within seconds of blocking or unblocking acetylcholine receptors at the mouse neuromuscular junction. Our data suggest that the homeostatic upregulation of release is due to Ca²⁺-dependent increase in the size of the readily releasable pool (RRP). Blocking vesicle refilling prevented upregulation of quantal content (QC), while leaving baseline release relatively unaffected. This suggested that the upregulation of QC was due to mobilization …

Cardiovascular Regulation And Effects Of Respiratory Motor Training In Patients With Chronic Spinal Cord Injury., Bonnie Legg Ditterline

Electronic Theses and Dissertations

This dissertation attempts to discover the mechanisms between cardiovascular and respiratory motor control post spinal cord injury (SCI): in normal, non-injured (NI) persons, cardiovascular regulation is dependent upon respiration, but there is nothing that suggests the mechanism for this relationship post-SCI. Thus we hoped to evaluate various aspects of cardiovascular regulation to further illustrate how this relationship is changed or unchanged by SCI. Chapter I describes the anatomy and physiology of the spine, respiratory system, and cardiovascular system in a NI person, and then describes how the function of these systems is changed by SCI. In addition, we describe therapies …

Plastin 3 Expression Does Not Modify Spinal Muscular Atrophy Severity In The ∆7 Sma Mouse, Vicki L. Mcgovern, Aurelie Massoni-Laporte, Xueyong Wang, Thanh T. Le, Hao T. Le, Mark M. Rich, Arthur H. M. Burghes

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal muscular atrophy is caused by loss of the SMN1 gene and retention of SMN2. TheSMN2 copy number inversely correlates with phenotypic severity and is a modifier of disease outcome. The SMN2 gene essentially differs from SMN1 by a single nucleotide in exon 7 that modulates the incorporation of exon 7 into the final SMN transcript. The majority of the SMN2transcripts lack exon 7 and this leads to a SMN protein that does not effectively oligomerize and is rapidly degraded. However theSMN2 gene does produce some full-length SMN and theSMN2 copy number along with how …

Appropriate Timing Of Fluoxetine And Statin Delivery Reduces The Risk Of Secondary Bleeding In Ischemic Stroke Rats, Maria Helen Harley Balch, Moner A. Ragas, Danny Wright, Kenny Reynolds, Bryce Kerr, Adrian M. Corbett

Neuroscience, Cell Biology & Physiology Faculty Publications

Background: Ongoing clinical trials are testing the effect of fluoxetine delivered post-stroke where a majority of patients are taking statins. This study determined the influence of the timing of administration of fluoxetine and statin on the final infarct volume and the risk of secondary bleeding in an animal model of ischemic stroke.

Methods and findings: Ischemic strokes were induced by endothelin-1 injection into two cortical sites of 10-12 month old female rats, targeting the forelimb motor cortex. Combined medications (5 mg/kg fluoxetine and 1 mg/kg simvastatin) were orally administered either beginning 6-12 hours or 20-26 hours after stroke induction and …

Swimming Against The Tide: Investigations Of The C-Bouton Synapse, Adam S. Deardorff, Shannon H. Romer, Patrick M. Sonner, Robert E. W. Fyffe

Neuroscience, Cell Biology & Physiology Faculty Publications

C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a “signaling ensemble”) for cholinergic regulation of outward K⁺ currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges …

Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Motoneuron synapses on spinal cord interneurons known as Renshaw cells activate nicotinic, AMPA and NMDA receptors consistent with co-release of acetylcholine and excitatory amino acids (EAA). However, whether these synapses express vesicular glutamate transporters (VGLUTs) capable of accumulating glutamate into synaptic vesicles is controversial. An alternative possibility is that these synapses release other EAAs, like aspartate, not dependent on VGLUTs. To clarify the exact EAA concentrated at motor axon synapses we performed a quantitative postembedding colloidal gold immunoelectron analysis for aspartate and glutamate on motor axon synapses (identified by immunoreactivity to the vesicular acetylcholine transporter; VAChT) contacting calbindin-immunoreactive (-IR) Renshaw …

Adult Spinal Motoneurones Are Not Hyperexcitable In A Mouse Model Of Inherited Amyotrophic Lateral Sclerosis, Nicolas Delestrée, Marin Manuel, Caroline Iglesias, Sherif M. Elbasiouny, C. J. Heckman, Daniel Zytnicki

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), an adult onset disease in which there is progressive degeneration of motoneurones, it has been suggested that an intrinsic hyperexcitability of motoneurones (i.e. an increase in their firing rates), contributes to excitotoxicity and to disease onset. Here we show that there is no such intrinsic hyperexcitability in spinal motoneurones. Our studies were carried out in an adult mouse model of ALS with a mutated form of superoxide dismutase 1 around the time of the first muscle fibre denervations. We showed that the recruitment current, the voltage threshold for spiking and the frequency–intensity gain in the …

Substance P Differentially Modulates Firing Rate Of Solitary Complex (Sc) Neurons From Control And Chronic Hypoxia-Adapted Adult Rats, Nicole L. Nichols, Frank L. Powell, Jay B. Dean, Robert W. Putnam

Neuroscience, Cell Biology & Physiology Faculty Publications

NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO₂/H⁺-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH …

Complexity Of Interferon-Γ Interactions With Hsv-1, Nancy J. Bigley

Neuroscience, Cell Biology & Physiology Faculty Publications

The intricacies involving the role of interferon-gamma (IFN-γ) in herpesvirus infection and persistence are complex. Herpes simplex virus type 1 (HSV-1) uses a variety of receptors to enter cells and is transported to and from the host cell nucleus over the microtubule railroad via retrograde and anterograde transport. IFN-γ exerts dual but conflicting effects on microtubule organization. IFN-γ stimulates production of suppressors of cytokine signaling 1 and 3 (SOCS1 and SOCS3), which are involved in microtubule stability and are negative regulators of IFN-γ signaling when overexpressed. IFN-γ also interferes with the correct assembly of microtubules causing them to undergo severe …

Nf1 Loss And Ras Hyperactivation In Oligodendrocytes Induce Nos-Driven Defects In Myelin And Vasculature, Debra A. Mayes, Tilat A. Rizvi, Haley E. Titus-Mitchell, Rachel Oberst, Georgianne M. Ciraolo, Charles V. Vorhees, Andrew P. Robinson, Stephen D. Miller, Jose A. Cancelas, Anat O. Stemmer-Rachamimov, Nancy Ratner

Neuroscience, Cell Biology & Physiology Faculty Publications

Patients with neurofibromatosis type 1 (NF1) and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB) developed, implicating a soluble mediator. Nitric oxide (NO) can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1-NOS3) were upregulated in mutant white matter. Treating mice with the NOS inhibitor …

Antioxidant Rescue Of Nf1/Ras-Induced Myelin And Vasculature Dysfunction, Debra A. Mayes, Tilat A. Rizvi, Shyra J. Miller, Rachel Oberst, Anat Stemmer-Rachamimov, Nancy Ratner

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.

Effect Of Synthetic Aβ Peptide Oligomers And Fluorinated Solvents On Kv1.3 Channel Properties And Membrane Conductance, Maria I. Lioudyno, Matteo Broccio, Yuri Sokolov, Suhail Rasool, Jessica Wu, Michael T. Alkire, Virginia Liu, J. Ashot Kozak, Philip R. Dennison, Charles G. Glabe, Mathias Lösche, James E. Hall

Neuroscience, Cell Biology & Physiology Faculty Publications

The impact of synthetic amyloid β (1–42) (Aβ_1–42) oligomers on biophysical properties of voltage-gated potassium channels Kv 1.3 and lipid bilayer membranes (BLMs) was quantified for protocols using hexafluoroisopropanol (HFIP) or sodium hydroxide (NaOH) as solvents prior to initiating the oligomer formation. Regardless of the solvent used Aβ_1–42 samples contained oligomers that reacted with the conformation-specific antibodies A11 and OC and had similar size distributions as determined by dynamic light scattering. Patch-clamp recordings of the potassium currents showed that synthetic Aβ_1–42 oligomers accelerate the activation and inactivation kinetics of Kv 1.3 current with no significant effect …

Loss Of Renal Allografts Secondary To Candida Vascular Complications In Two Recipients From The Same Donor, Govardhana R. Yannam, Lucile E. Wrenshall, R. Brian Stevens

Neuroscience, Cell Biology & Physiology Faculty Publications

Infections remain a major cause of morbidity and mortality in transplant patients. Organ recipients are also susceptible to donor-derived pathogens and the majority of donor infections are easily treatable. Rarely, some pathogens have produced life-threatening complications by compromising the vascular anastomosis. In this case series we report loss of two kidney allografts secondary to vascular complications due to Candida albicans. Both recipients received grafts from a common donor, in whom Candida bacteremia in the donor was not apparent at the time of organ acceptance but became apparent on delayed cultures.

Electronic Nose Based On Independent Component Analysis Combined With Partial Least Squares And Artificial Neural Networks For Wine Prediction, Teodoro Aguilera, Jesús Lozano, José A. Paredes, Francisco J. Alvarez, José I. Suárez

Neuroscience, Cell Biology & Physiology Faculty Publications

The aim of this work is to propose an alternative way for wine classification and prediction based on an electronic nose (e-nose) combined with Independent Component Analysis (ICA) as a dimensionality reduction technique, Partial Least Squares (PLS) to predict sensorial descriptors and Artificial Neural Networks (ANNs) for classification purpose. A total of 26 wines from different regions, varieties and elaboration processes have been analyzed with an e-nose and tasted by a sensory panel. Successful results have been obtained in most cases for prediction and classification.

Electrophysiological Abnormalities In Sod1 Transgenic Models In Amyotrophic Lateral Sclerosis: The Commonalities And Differences, Sherif M. Elbasiouny, Katharina Quinlan, Tahra L. Eissa, Charles J. Heckman

Neuroscience, Cell Biology & Physiology Faculty Publications

Since its first description in 1874 by Charcot, the hallmark feature of ALS is the progressive degeneration of upper and lower motoneurons (Charcot, 1874). In the spinal cord, motoneuron degeneration starts long before symptom onset and advances in a size-related fashion, in which large-size alpha-motoneurons degenerate first followed by small-size alpha-motoneurons (Pun et al., 2006; Hegedus et al., 2007; Hegedus et al., 2008). There are conflicting reports regarding the survival of the smallest-sized spinal motoneurons, the gamma-motoneurons (Swash and Fox, 1974; Sobue et al., 1981). Despite its original description, the neuronal degeneration in ALS is not limited to motoneurons. Recent …