SEARCH · PubMed Health

Results for “selective vulnerability”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources

PubMed2003

Flow cytometric analysis of mitochondria from CA1 and CA3 regions of rat hippocampus reveals differences in permeability transition pore activation.

Mitochondria are important in the pathophysiology of several neurodegenerative diseases, and mitochondrial production of reactive oxygen species (ROS), membrane depolarization, permeability changes and release of apoptogenic proteins are involved in these processes. Following brain insults, cell death often occurs in discrete regions of the brain, such as the subregions of the hippocampus. To analyse mitochondrial structure and function in such subregions, only small amounts of mitochondria are available. We developed a protocol for flow cytometric analysis of very small samples of isolated brain mitochondria, and analysed mitochondrial swelling and formation of ROS in mitochondria from the CA1 and CA3 regions of the hippocampus. Calcium-induced mitochondrial swelling was measured, and fluorescent probes were used to selectively stain mitochondria (nonyl acridine orange), to measure membrane potential (tetramethylrhodamine-methyl-ester, 1,1',3,3,3',3'-hexamethylindodicarbocyanine-iodide) and to measure production of ROS (2',7'-dichlorodihydrofluorescein-diacetate). We found that formation of ROS and mitochondrial permeability transition pore activation were higher in mitochondria from the CA1 than from the CA3 region, and propose that differences in mitochondrial properties partly underlie the selective vulnerability of the CA1 region to brain insults. We also conclude that flow cytometry is a useful tool to analyse the role of mitochondria in cell death processes.

Animals↗

PubMed2004

Proteasome inhibition and aggregation in Parkinson's disease: a comparative study in untransfected and transfected cells.

Dysfunction of the ubiquitin-proteasome system (UPS) has been implicated in Parkinson's disease (PD) and other neurodegenerative disorders. We have investigated the effect of UPS inhibition on the metabolism of alpha-synuclein (SYN) and parkin, two proteins genetically and histopathologically associated to PD. Pharmacological inhibition of proteasome induced accumulation of both parkin and SYN in transfected PC12 cells. We found that this effect was caused by increased protein synthesis rather than impairment of protein degradation, suggesting that inhibition of the UPS might lead to non-specific up-regulation of cytomegalovirus (CMV)-driven transcription. To investigate whether endogenous parkin and SYN can be substrate of the UPS, untransfected PC12 cells and primary mesencephalic neurones were exposed to proteasome inhibitors, and parkin and SYN expression was evaluated at both protein and mRNA level. Under these conditions, we found that proteasome inhibitors did not affect the level of endogenous parkin and SYN. However, we confirmed that dopaminergic neurones were selectively vulnerable to the toxicity of proteasome inhibitors. Our results indicate that studies involving the use of proteasome inhibitors, particularly those in which proteins are expressed from a heterologous promoter, are subjected to potential artefacts that need to be considered for the interpretation of the role of UPS in PD pathogenesis.

Animals↗

PubMed2003

Reduced age-related plasticity of neurotrophin receptor expression in selected sympathetic neurons of the rat.

Selective vulnerability of particular groups of neurons is a characteristic of the aging nervous system. We have studied the role of neurotrophin (NT) signalling in this phenomenon using rat sympathetic (SCG) neurons projecting to cerebral blood vessels (CV) and iris which are, respectively, vulnerable to and protected from atrophic changes during old age. RT-PCR was used to examine NT expression in iris and CV in 3- and 24-month-old rats. NGF and NT3 expression in iris was substantially higher compared to CV; neither target showed any alterations with age. RT-PCR for the principal NT receptors, trkA and p75, in SCG showed increased message during early postnatal life. However, during mature adulthood and old age, trkA expression remained stable while p75 declined significantly over the same period. In situ hybridization was used to examine receptor expression in subpopulations of SCG neurons identified using retrograde tracing. Eighteen to 20 h following local treatment of iris and CV with NGF, NT3 or vehicle, expression of NT receptor protein and mRNA was higher in iris- compared with CV-projecting neurons from both young and old rats. NGF and NT3 treatment had no effect on NT receptor expression in CV-projecting neurons at either age. However, similar treatment up-regulated p75 and trkA expression in iris-projecting neurons from 3-month-old, but not 24-month-old, rats. We conclude that lifelong exposure to low levels of NTs combined with impaired plasticity of NT receptor expression are predictors of neuronal vulnerability to age-related atrophy.

Adrenergic Fibers↗

PubMed2002

Neuropathology associated with stillbirth.

Neuropathologic findings in stillbirths oftentimes provide insight into the specific mechanisms leading to death. Examination of the brains of stillborn infants may also identify pathophysiologic processes that result in prenatal brain injury in liveborn as well as stillborn infants and that lead to neurologic disorders in liveborn infants, such as cerebral palsy or the sudden infant death syndrome (SIDS). A variety of abnormalities are found in the brains of stillborns, the most common including cerebral white matter necrosis (periventricular leukomalacia) or gliosis, germinal matrix or intraventricular hemorrhage, cerebral infarcts, pontosubicular necrosis, and spinal cord or brainstem necrosis. The 2 major hypotheses that have been proposed for the pathophysiology of cerebral white matter injury in the perinatal period are hypoxia/ischemia and infection/cytokines as the basis for injury. The fetal brain may be selectively vulnerable to various insults at specific stages of development.

Brain↗

PubMed2001

Nuclear gene defects in respiratory chain disorders.

Deficiencies in the activity of the components of the mitochondrial respiratory chain can result from mutations in genes encoded in the mitochondrial (mtDNA) or nuclear genomes. Mutations in mtDNA have been identified over the past decade in a wide spectrum of clinical disorders, and attention has now turned to identifying nuclear gene defects. Positional cloning, candidate gene analysis, and functional complementation in patient cell lines have all been used with success. Mutations in gene coding for structural subunits of the respiratory chain complexes appear to be less numerous than defects in genes associated with some aspect of the biogenesis of the respiratory chain. Despite the fact that many of the nuclear disease genes so far identified are ubiquitously expressed, tissue specificity of the biochemical and clinical phenotype is the rule rather than the exception. This selective vulnerability of different cell populations remains unexplained. The majority of patients with a biochemical deficiency in one or the other of the respiratory chain complexes do not yet have a molecular diagnosis.

Education, Medical, Continuing↗

PubMed1996

[Posterior cortical atrophy--a new dementia syndrome or a form of Alzheimer's disease?].

Posterior Cortical Atrophy (PCA) is a neurodegenerative disorder initially dominated by disturbances in higher visual functions including object agnosia, prosopagnosia, alexia, environmental agnosia and Balint's syndrome. Language, memory, insight, and judgement remain relatively preserved until late in the course. A characteristic neuroradiological finding consists of focal bilateral parieto-occipital atrophy demonstrated on MRI and CT. It was speculated that the possible underlying pathologic condition could be an atypical clinical variant of Alzheimer's disease, a lobar atrophy analogous to Pick's disease, a variant of Creutzfeldt-Jakob disease or some previously unrecognized entity. The prognostic question whether the visual agnostic symptoms are only a precursor of generalized dementia remained unsolved. The neuropsychological symptoms in these patients indicate that the occipitoparietal cortex is bilaterally affected which is in contrast to the parietotemporal distribution of lesions in Alzheimer's disease and the frontotemporal type of distribution in Pick's disease. The aim of this study was to review and analyze all cases of posterior cortical atrophy which have been reported in the literature. Up to now 58 cases of posterior cortical atrophy have been described. The first report of such a patient was given by A. Pick in 1902. The results of our analysis show that posterior cortical atrophy is mainly a presenile disorder which in most cases heralds the development of generalized dementia. The histopathological results suggest that the combination of clinical findings referred to as PCA can result from strikingly different pathological entities. However, most cases of PCA which were investigated postmortem revealed the histopathological lesion type of Alzheimer's disease. This suggests that PCA is rather a subgroup of Alzheimer's disease than an independent disease. This conclusion has some implication for the nosological classification of other localized slowly progressive syndromes such as slowly progressive aphasia. These syndromes may as well define possible clinical subgroups of the "classical" dementias. They show that the close relationship between the clinical profile and the brain regions involved does not necessarily imply a specific neuropathological process but focus the attention on the selective vulnerability of distinct neuronal systems.

Adult↗

PubMed2004

Founders' Lecture. Human spermatozoa: fruits of creation, seeds of doubt.

Deoxyribonucleic acid damage in the male germline is associated with defective fertilisation, impaired embryonic development, reduced implantation, abortion and childhood disease. Oxidative stress and the retention of excess residual cytoplasm by the spermatozoa are frequently associated with the induction of such damage. The redox cycling of xenobiotics by oxido-reductases in the germline, the patient's age, the incidence of genital tract infections and Sertoli cell dysfunction are all possible contributors to DNA damage in germ cells. Collateral peroxidation of unsaturated fatty acids in the sperm plasma membrane generally ensures that spermatozoa experiencing severe oxidative DNA damage cannot participate in the process of fertilisation. The adaptive termination of pregnancy through the selective vulnerability of genes involved in placentation may also help prevent the vertical transmission of damaged DNA. However, the ultimate safeguard against this form of damage will be to understand the biochemical basis of oxidative stress in human spermatozoa, so that the underlying causative mechanisms can be addressed in a logical manner.

Chromosome Deletion↗

PubMed1996

Relation between cerebral oxygen delivery and neuronal cell damage in fetal sheep near term.

Asphyxia is one of the major causes for fetal brain damage. Although the quality of life of the so affected children is mostly very limited, the pathogenesis of hypoxic fetal brain damage is poorly understood. Particularly, there is a lack of studies, in which cerebral oxygen delivery is directly correlated to the extent of neuronal cell damage in the same brain specimens. Therefore, we measured cerebral oxygen delivery before (- 1 h), during (+3 min & +27 min) and after (+10 min, +4 h, +72 h) 30 min of ischaemia in 5 chronically catheterized normoxemic fetal sheep at 129 +/- 1 days gestation (term is at 147 days) using the microsphere method. In contrast to previous studies (Williams et al. 1990), we arrested carotid arterial blood flow above the lingual artery for 30 min during surgery. Seventy-two hours later the fetal brains were fixed in vivo under barbiturate anaesthesia of both the fetus and the ewe. After cerebral blood flow analysis neuronal cell damage was assessed with light microscopy in 43 specimens of the fetal brain after cresyl violet/fuchsin staining using a scoring system. After arrest of carotid arterial blood flow cerebral blood flow was reduced by 80%. Neuronal cell damage was focussed on the cerebral cortex. Almost no damage could be detected in deeper parts of the brain. In the cerebrum there was threshold oxygen delivery of 3 ml O2/100 g tissue/min, below which neuronal damage occurred. However, there was no correlation between cerebral oxygen delivery and neuronal cell damage in specimens of the cerebrum, in which oxygen delivery was less than 3 ml O2/100 g tissue/min, suggesting selective vulnerability. Therefore, in addition to the reduction in cerebral oxygen delivery, other variables, e.g. neurotransmitter release, receptor pattern or oxygen radicals, may be involved in the development of brain damage.

Analysis of Variance↗

PubMed2003

Transforming growth factor beta1 induction of vascular endothelial growth factor receptor 1: mechanism of pericyte-induced vascular survival in vivo.

Degeneration of vessels precedes and precipitates the devastating ischemia of many diseases, including retinopathy of prematurity and diabetic retinopathy. Ischemia then leads to proliferative retinopathy and blindness. Understanding the mechanisms of blood vessel degeneration is critical to prevention of these diseases. Vessel loss is associated with oxygen-induced suppression of vascular endothelial growth factor (VEGF) and with pericyte (vascular smooth muscle cell) dropout. The molecular mechanism of pericyte protection of the vasculature is unknown. We show that transforming growth factor beta1 (TGF-beta1)-expressing pericytes are specifically found on vessels resistant to oxygen-induced loss. TGF-beta1 potently induces VEGF receptor 1 (VEGFR-1) expression in endothelial cells and thereby prevents oxygen-induced vessel loss in vivo. Vessel survival is further stimulated with a VEGFR-1-specific ligand, placental growth factor 1. TGF-beta1 induction of VEGFR-1 in endothelial cells explains pericyte protection of vessels and the selective vulnerability of neonatal vessels to oxygen. These results implicate induction and activation of VEGFR-1 as critical targets to prevent vessel loss.

Animals↗

PubMed1992

Enhanced sensitivity of hippocampal pyramidal neurons from mdx mice to hypoxia-induced loss of synaptic transmission.

The gene at the Duchenne/Becker muscular dystrophy locus encodes dystrophin, a member of a protein superfamily that links the actin cytoskeleton to transmembrane plasmalemmal proteins. In mature skeletal myocytes, the absence of dystrophin is associated with decreased membrane stability, altered kinetics of several calcium channels, and increased intracellular calcium concentration. In the central nervous system, dystrophin is restricted to specific neuronal populations that show heightened susceptibility to excitotoxic damage and is localized in proximal dendrites and the neuronal somata. We report that CA1 pyramidal neurons in a hippocampal slice preparation from a dystrophin-deficient mouse genetic model of Duchenne muscular dystrophy (the mdx mouse) exhibit significant increased susceptibility to hypoxia-induced damage to synaptic transmission. This selective vulnerability was substantially ameliorated by pretreatment with diphenylhydantoin, an anticonvulsant that blocks both sodium-dependent action potentials and low-threshold transient calcium conductances. These findings suggest that dystrophin deficiency could predispose susceptible neuronal populations to cumulative hypoxic insults that may contribute to the development of cognitive deficits in Duchenne/Becker muscular dystrophy patients and that the effects of such periods of hypoxia may be pharmacologically remediable.

Animals↗

PubMed1993

Phospholipase D-catalyzed hydrolysis of phosphatidylcholine provides the choline precursor for acetylcholine synthesis in a human neuronal cell line.

To identify the metabolic pathway that generates choline (Cho) for acetylcholine (AcCho) from its storage pool in membrane phosphatidylcholine (PtdCho), human neuronal cells (LA-N-2) were radioisotopically labeled with 1-O-hexadecyl-2-hydroxy-sn-glycero(3)phospho[14C]choline. The compound was efficiently taken up by the cells and metabolically labelled PtdCho, Cho, AcCho, and phosphocholine pools. In pulse-chase experiments, the specific radioactivities of the metabolites of 1-O-hexadecyl-2-hydroxy-sn-glycero(3)-phospho[14C]choline indicated that it was rapidly acylated to Ptd-Cho and then hydrolyzed first to free Cho and not to phosphocholine or glycerophosphocholine. This Cho was subsequently converted to AcCho and to phosphocholine. In the absence of exogenous Cho, at least 15% of the total cellular AcCho pool was synthesized by this pathway in 1 h. The data demonstrate that the liberation of the free Cho precursor for AcCho synthesis from PtdCho can be accomplished in a one-step process, indicating the involvement of a phospholipase D-type enzyme. In the presence of hemicholinium-3, which inhibits Cho transport, the amount of intracellular [14C]Cho metabolites that accumulated during the chase period was higher than in control cells, indicating that PtdCho hydrolysis liberated Cho directly into the cytoplasm. These data show that cholinergic cells are characterized by an intracellular pathway, catalyzed by a phospholipase D, that generates Cho for AcCho synthesis from PtdCho. Abnormalities in the regulation of this pathway may contribute to selective vulnerability of cholinergic neurons in certain neurodegenerative diseases, e.g., Alzheimer disease.

Acetylcholine↗

PubMed1994

Prostaglandin E2 elicits a morphological change in cultured orbital fibroblasts from patients with Graves ophthalmopathy.

Fibroblasts derived from distinct anatomical regions appear to differ in regard to their behavior in culture. These differences may reflect functions of these cells in vivo that are tissue specific. Moreover, intrinsic differences in fibroblasts may underlie the site-specific connective tissue manifestations associated with systemic disease. We have demonstrated previously that orbital fibroblasts exhibit different cytokine response domains and protein synthetic programs when compared to those emanating from the skin. In the present communication, we demonstrate that prostaglandin E2 (PGE2) elicits in cultured human orbital fibroblasts from patients with Graves ophthalmopathy a rapid and dramatic change in cell morphology in vitro as assessed by phase-contrast and scanning electron microscopy. The central areas of the cells become elevated with respect to the plane of the substratum and are stellate, with long processes that touch neighboring cells. These changes occur within 6 hr of prostanoid addition to culture medium at an apparent concentration threshold of approximately 10 nM. Shape changes are accompanied by marked alterations in monolayer impedance as assessed by electric cell-substrate impedance sensing as described previously. Both morphologic and impedance changes elicited by PGE2 revert over 24 hr toward those found in untreated cells despite the continued presence of the prostanoid in the culture medium. In contrast, dermal fibroblasts fail to respond to PGE2. These observations define a previously unrecognized phenotypic attribute of orbital fibroblasts. Intrinsic differences in these cells may account for the anatomic site-selective vulnerability of the orbit in Graves ophthalmopathy. The culture system described here may be useful for studying the morphogenic actions of prostanoids.

Cells, Cultured↗

PubMed1996

Expression of calbindin-D28K in motoneuron hybrid cells after retroviral infection with calbindin-D28K cDNA prevents amyotrophic lateral sclerosis IgG-mediated cytotoxicity.

Calbindin-D28K and/or parvalbumin appear to influence the selective vulnerability of motoneurons in amyotrophic lateral sclerosis (ALS). Their immunoreactivity is undetectable in motoneurons readily damaged in human ALS, and in differentiated motoneuron hybrid cells [ventral spinal cord (VSC 4.1 cells)] that undergo calcium-dependent apoptotic cell death in the presence of ALS immunoglobulins. To provide additional evidence for the role of calcium-binding proteins in motoneuron vulnerability, VSC 4.1 cells were infected with a retrovirus carrying calbindin-D28K cDNA under the control of the promoter of the phosphoglycerate kinase gene. Differentiated calbindin-D28K cDNA-infected cells expressed high calbindin-D28K and demonstrated increased resistance to ALS IgG-mediated toxicity. Treatment with calbindin-D28K antisense oligodeoxynucleotides, which significantly decreased calbindin-D28K expression, rendered these cells vulnerable again to ALS IgG toxicity.

Amyotrophic Lateral Sclerosis↗

PubMed1999

Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides.

The excessive generation and accumulation of 40- and 42-aa beta-amyloid peptides (Abeta40/Abeta42) in selectively vulnerable brain regions is a major neuropathological feature of Alzheimer's disease. Abeta, derived by proteolytic cleavage from the beta-amyloid precursor protein (betaAPP), is normally secreted. However, recent evidence suggests that significant levels of Abeta also may remain inside cells. Here, we have investigated the subcellular compartments within which distinct amyloid species are generated and the compartments from which they are secreted. Three experimental approaches were used: (i) immunofluorescence performed in intact cortical neurons; (ii) sucrose gradient fractionation performed with mouse neuroblastoma cells stably expressing wild-type betaAPP695 (N2a695); and (iii) cell-free reconstitution of Abeta generation and trafficking from N2a695 cells. These studies demonstrate that: (i) Abeta40 (Abeta1-40 plus Abetax-40, where x is an NH2-terminal truncation) is generated exclusively within the trans-Golgi Network (TGN) and packaged into post-TGN secretory vesicles; (ii) Abetax-42 is made and retained within the endoplasmic reticulum in an insoluble state; (iii) Abeta42 (Abeta1-42 plus Abetax-42) is made in the TGN and packaged into secretory vesicles; and (iv) the amyloid peptides formed in the TGN consist of two pools (a soluble population extractable with detergents and a detergent-insoluble form). The identification of the organelles in which distinct forms of Abeta are generated and from which they are secreted should facilitate the identification of the proteolytic enzymes responsible for their formation.

Alzheimer Disease↗

PubMed2000

Reduction of axonal caliber does not alleviate motor neuron disease caused by mutant superoxide dismutase 1.

It is well established that motor neurons with large axon caliber are selectively affected in amyotrophic lateral sclerosis (ALS). To investigate whether high neurofilament (NF) content and large axonal caliber are factors that predispose motor neurons to selective degeneration in ALS, we generated mice expressing a mutant form of superoxide dismutase 1 (SOD1(G37R)) linked to familial ALS in a context of one allele for each NF gene being disrupted. A approximately 40% decrease of NF protein content detected in triple heterozygous knockout mice shifted the calibers of large axons in L5 ventral root from 5-9 microm to 1-5 microm, altering neither the normal subunit stoichiometry and morphological distribution of NFs nor levels of other cytoskeletal proteins. This considerable reduction in NF burden and caliber of axons did not extend the life span of SOD1(G37R) mice nor did it alleviate the loss of motor axons. Moreover, increasing the density of NFs in axons by overexpressing a NF-L transgene did not accelerate disease in SOD1(G37R) mice. These results do not support the current view that high NF content and large caliber of axons may account for the selective vulnerability of motor neurons in ALS caused by mutant SOD1.

Alleles↗

PubMed2006

DJ-1 transcriptionally up-regulates the human tyrosine hydroxylase by inhibiting the sumoylation of pyrimidine tract-binding protein-associated splicing factor.

Loss-of-function mutations in DJ-1 cause a subset of familial Parkinson disease (PD). However, the mechanism underlying the selective vulnerability in dopaminergic pathway due to the inactivation of DJ-1 is unclear. Previously, we have reported that DJ-1 is a neuroprotective transcriptional co-activator interacting with the transcriptional co-repressor pyrimidine tract-binding protein-associated splicing factor (PSF). Here we show that DJ-1 and PSF bind and regulate the human tyrosine hydroxylase (TH) promoter. Inactivation of DJ-1 by small interference RNA (siRNA) results in decreased TH expression and l-DOPA production in human dopaminergic cell lines. Consistent with its role as a transcriptional regulator, DJ-1 specifically suppresses the global SUMO-1 modification. High molecular weight sumoylated protein species, including PSF, accumulate in the lymphoblast cells from the patients carrying pathogenic DJ-1 mutations. DJ-1 elevates the TH expression by inhibiting the sumoylation of PSF and preventing its sumoylation-dependent recruitment of histone deacetylase 1. Furthermore, siRNA silencing of DJ-1 decreases the acetylation of TH promoter-bound histones, and histone deacetylase inhibitors restore the DJ-1 siRNA-induced repression of TH. Therefore, our results suggest DJ-1 as a regulator of protein sumoylation and directly link the loss of DJ-1 expression and transcriptional dysfunction to impaired dopamine synthesis.

Humans↗

PubMedDate not supplied

The mossy fiber system of the hippocampal formation is decreased by chronic and postnatal but not by prenatal protein malnutrition in rats.

We tested in 70-day-old Sprague-Dawley rats, whether malnutrition imposed during different periods of hippocampal development produced deleterious effects on the total reference volume of the mossy fiber system. Animals were treated under four nutritional conditions: (a) well nourished; (b) prenatal protein malnourished; (c) chronic protein malnourished and (d) postnatal protein malnourished. Timm's stained material was used in coronal hippocampal sections (40 microm) to estimate--using the Principle of Cavalieri--the total reference volume of the mossy fiber system in each experimental group. Our results show that chronic and postnatal protein malnourished, but not prenatal malnourished rats, decrease the mossy fiber system and the total reference volume of the mossy fiber system are selectively vulnerable to the type of dietary restriction. Thus, chronic and posnatal protein malnutrition produce deleterious effects, but only rats under prenatal protein malnutrition were able to reorganize synapses in this plexus. These findings raise the possibility that chronic malnutrition, as a long-term stressful factor, might be an important paradigm to test structural hippocampal changes that produce physiological and pathophysiological effects, or the possibility to recover its function for nutritional rehabilitation.

Animals↗

PubMed2000

Peristimulus time histograms (PSTHs)--a marker for upper motor neuron involvement in ALS?

Upper motor neuron involvement in ALS has been widely studied by means of transcranial magnetic stimulation and various imaging methods, such as magnetic resonance imaging, proton emission tomography, single photon emission computer tomography and magnetic resonance spectroscopy. Although almost all of these methods have detected 'abnormalities' of the motor cortex, no method has yet proven to be capable of monitoring disease progression. We and others have used peristimulus time histograms (PSTH) to evaluate corticomotoneuronal dysfunction. The primary peak (PP) in the PSTH reflects the initial rising phase of the excitatory post-synaptic potential evoked at the anterior horn cell by converging corticomotoneurons. In ALS, the PP is delayed in onset, increased in duration, and desynchronized. These abnormalities become more pronounced over time. Delayed PPs also occur more frequently in non-hereditary ALS (nHALS) with disease progression and are a hallmark of the autosomal recessively inherited D90A Cu-Zn SOD mutation. Evidence indicates that in this particular mutation, as well as in nHALS, the fast-conducting monosynaptic pathway originating from large pyramidal Betz cells is preferentially lost, whereas a slow-conducting pathway seems to be spared. This is most likely due to the enormous metabolic demand of the large pyramidal cells, which may explain the selective vulnerability of the most recent phylogenetic system to develop in the human nervous system.

Amyotrophic Lateral Sclerosis↗