Transcript Document

Molecular, Cellular and Developmental Neuroscience
January 15, 2008 9-10:50 am
Organelle Synthesis and Axonal Transport
Lecturer: Professor Eileen M. Lafer
Contact Info.: 415B, 567-3764, [email protected]
Recommended Reading: From Molecules to Networks, Chapter
2, pp. 31-66.
REMINDER ALL MY LECTURE MATERIALS ARE POSTED AT:
http://biochem.uthscsa.edu/~lafer/classlinks.html
Basic Elements
of Neuronal
Subcellular
Organization:
Neurofilaments
Microtubules
The Cytoskeletons of Neurons and Glia
(and all eukaryotic cells!)
(see tables 2.2, 2.3, 2.4 for complete list)
Microtubules (Tubulin)Tubulins, MAPs, Motors: Kinesins and Dyneins
Microfilaments (Actin)Actins, Actin Monomer Binding Proteins, Capping Proteins, Gelsolin Family, Crosslinking
and Bundling Proteins, Tropomyosin, Motors: Myosin
Intermediate Filaments- Superfamily of 5 classes:
Types I and II: Keratins, Type III: GFAP, Vimentin, Desmin, Peripherin, Type IV: NF Triplet,
Internexin, Nestin, Type V: Nucelar Laminins
Slow Axonal Transport:
~1-4 mm/day
Purpose:
Delivery of cytosolic and
cytoskeletal proteins to
the nerve terminal:
Microtubules
Neurofilaments
Enzymes
Fast Axonal Transport:
100-400 mm/day
Purpose: Transport
organelles such as
mitochondira and vesicles
carrying SV and plasma
membrane proteins to the
nerve terminal.
Also retrograde
movement of vesicles
containing neurotrophic
factors back to the cell
body.
Principal members of kinesin superfamily proteins
(KIFs) observed by lowangle rotary shadowing
Structures of N-kinesins, M-kinesins and Ckinesins
Kinesin superfamily proteins (KIFs) and cargoes
for axonal and dendritic transport.
Kinesin superfamily proteins (KIFs) bind to
cargoes through adaptor or scaffolding protein
complexes.
Kinesin superfamily protein 5 (KIF5) and its
selective transport to axons and dendrites.
SYNAPTIC VESICLE BIOGENESIS
STUDENT ASSIGNMENT:
Write two F1000 style reviews of papers
that interest you pertaining to the general
topic of axonal transport and
neurodegeneration. Be prepared to discuss
your reviews with the class.
Margaret Wey
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Article #1
Must ReadRank: 6.0Axonopathy and transport deficits early in the pathogenesis of Alzheimer's
disease. Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, Raman R, Davies P,
Masliah E, Williams DS, Goldstein LS Science 2005 Feb 25; 307(5713):1282-8 [PubMed] [pdf] [Faculty
1000]CommentsThis is an interesting article about axonopathy to be one of the pathology of Alzheimer’s
disease (AD). The investigation were performed in both mouse AD models and human AD patients. The
authors discovered axonal swelling in the early stage of AD, which is controversy to previous studies.
They used different immunostaining methods to demonstrate that axonal blockade/swelling can cause
impaired axonal transport, abnormal organelle accumulation, Aβ formation and amyloid deposition.
Therefore, axonal transport deficits, instead of being a result of AD progression, it may play an early and
potential causative role in AD and become a vicious cycle.
Article #2
RecommendedRank: 3.0In vivo axonal transport rates decrease in a mouse model of Alzheimer's
disease. Smith KD, Kallhoff V, Zheng H, Pautler RG Neuroimage 2007. May 1; 35(4):1401-8 [PubMed]
[pdf]CommentsThis paper used Manganese Enhanced MRI (MEMRI), a non-invasive imaging
technique, to quantify axonal transport rate in transgenic mouse model of Alzheimer’s disease (AD).
They were able to show the axonal transport rate difference in wild type and transgenic mice; moreover,
the rate decreased with age. This axonal transport rate reduction can be seen prior to Aβ plaque formation
and amyloid accumulation, which MEMRI may be tool for detecting early physiological deficits and
characterize disease states. However, the cause of axonal transport deficits can not be identified.
Wei Liu
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Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Stokin GB, Lillo C, Falzone TL, Brusch RG,
Rockenstein E, Mount SL, Raman R, Davies P, Masliah E, Williams DS, Goldstein LS Science 2005 Feb 25 307(5713):1282-8
The significance of this paper is to provide the first in vivo evidence linking a deficit in axonal transport to Alzheimer's disease (AD). In this
paper, the authors examined the role of axonal defects in mouse models of Alzheimei's Disease (AD) and also looked for similar effects in
human post mortem brain tissue from AD patients. There are a number of very important and interesting observations in this paper. The
authors observed axonal swellings, which is characteristic of axonal injury, proceded amyloid and other disease-related pathology in mouse
AD model. It also occure early in human AD. The authors also reduced kinesin, finding enhanced freauency of axonal defects and increased
amyloid-beta peptide levels in amyloid deposition. Therefore, the authors hypothesized thatdefects in axonal transort may stimulate
proteolytic processing of ß-amyloid precursor protein, resulting in the development of senile plaques and Alzheimer's disease.
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Kinesin and dynein move a peroxisome in vivo: a tug-of-war or coordinated movement? Kural C, Kim H, Syed S, Goshima G, Gelfand VI,
Selvin PR Science 2005 Jun 3 308(5727):1469-72
The significance of the research is by using advanced imaging techniques, the authors provide compelling evidence supporting 'coordinated
movement' model for motor protein activity, instead of 'tug-of-war' model. By fluorescence imaging with one nanometer accuracy (FIONA)
of GFP labled peroxisomes inside living cells , the authors found that living cells allow only 8nm steps made by kinesin and cytoplasmic
dynein. Because intermediate step sizes are expected in a tug of war model, therefore the authors proposed that multiple kinesins or multiple
dyneins work together, producing up to 10 times the in vitro speed, through coordinated movement.
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Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF. Pun S, Santos AF, Saxena S,
Xu L, Caroni P Nat Neurosci 2006 Mar 9(3):408-19
The significance of this paper is that it is the first study to show that in two mouse models of motoneuron disease (G93A SOD1 and G85R
SOD1), axons of fast-fatiguable motoneurons are affected synchronously, long before symptoms appear. Fast-fatigue-resistant motoneuron
axons are affected at symptom-onset, whereas axons of slow motoneurons are resistant. Differences in axon vulnerability affects synaptic
vesicle stalling and apoptosis.The paper also shows that early vulnerability of axon terminals can be allevated by ciliary neurotrophic
factor(CNTF) but surprisingly not by glial cell line-derived neurotrophic factor(GDNF). This study could also shed some light on
understanding the mechanisms of other other neurodegenerative diseases that are induced by deficits in ason terminals.
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Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Zhao C, Takita J, Tanaka Y, Setou M,
Nakagawa T, Takeda S, Yang HW, Terada S, Nakata T, Takei Y, Saito M, Tsuji S, Hayashi Y, Hirokawa N Cell 2001 Jun 1 105(5):587-97
The significance of this paper is that it is the first direct demonstration that a loss of function mutation in a microtubule motor gives rise to a
neurodegenerative disease. The authors showed patients that have motor and sensory peripheral neuropathy Charcot-Marie-Tooth Type 2A
(CMT2A) carry a loss-of-function mutation in the motor domain of the KIF1B gene. Furthermore, KIF1B heterozygotes mice suffer from
progressive muscle weakness similar to human neuropathies. In addition, the authors speculate that this athology results from the defect in
transporting synaptic vesicle precursors. Indeed, indentification of the transported synaptic vesicle precursors remains a key issue in this
field of study.
Yu Tao
Luke Whitemire
– Ebneth A, GodemannR, Stamer K, Illenberger S, Trinczek B, Mandelkow E. Overexpression of Tau
Protein Inhibits Kinesin-dependent Trafficking of Vesicles, Mitochondria, and Endoplasmmic
Reticulum: Implications for Alzheimer’s Disease. 1998. F.Cell. Biol. 143:777-94
– This research is important because, historically the concentration of tau protein is elevated in brain
tissues that have been associated with Alzheimer’s disease. This paper observes that slightly
elevated tau levels lead to peroxisome and mitochondrial clustering at the microtubule organizing
center, contraction of the intermediate filament system and the ER, and leads to a reduced rate of
exocytosis. This is accomplished without disruption of the microtubule network. Tau proteins
interfere with the plus-end-directed transport along microtubules. As result, cell growth slows,
looses its elongated shape, and processes dependent on the ER and mitochondria are reduced.
– 3. It provides important insight into the biochemical role of tau proteins.
– Niewiadomska G, Baksalerska-Pazera M. Age-dependent changes in axomal transport and cellular
distribution of Tau1 in the rat basal forebrain neurons. 2003. Neuroreport 14:1701-6
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This research parallels a decreased level of retrograde axonal transport activity in aging neurons
with altered compartmentalization of tau izoform in neurons of the basal forebrain and
hippocampus. A significant difference is appreciated in the mean population of fluorogold positive
neurons between the young and aged groups. This coincides with the appreciation of tau1
localization to the axon in young neurons and the redistribution of tau1 proteins to the cell bodies of
the aged groups.
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3. This provides a link between neurodegeneration and a specific tau protein that encourages a
foundation for future study.
Harinder Singh
1. Lithium reduces tau phosphorylation but not A beta or working memory deficits in a transgenic model with both
plaques and tangles.
Antonella Caccamo, Salvatore Oddo, Lana X. Tran, and Frank M. LaFerla
Am J Pathol. 2007 May;170(5):1669-75
Faculty of 1000 Review: F1000 Factor- 6
1.This is interesting research as Lithium till now known for mood stabilization is having neuroprotective roles also. This
hints at common mechanism for affective as well as neurodegenerative disorders opening further avenues for psychiatry.
2.They showed therapeutic effects of Lithium in controlling onset and progression of Alzheimer’s disease by decreasing
Tau Phosphorylation via reduction in GSK-α and β activity.
3.Transgenic AD mice with and without lithum showed differences in brain histology and protein expression of GSK-α
and β using immunohistochemistry and ELISA techniques.
2. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons.
Makiko Nagai, Diane B Re, Tetsuya Nagata, Alcmène Chalazonitis, Thomas M Jessell, Hynek Wichterle, Serge
Przedborski.
Nature Neuroscie. 2007 May;10(5):615-22.
Faculty of 1000 Review: F1000 Factor-3
1.Interesting finding that neuronal supporting cells, astrocytes and microglia with mutated SOD-1 toxic to motor
neurons.
2.The paper shows specific effect of SOD-1 mutant astrocytes and microglia on degeneration of Primary spinal neurons
and Embryonic cell derived motor neurons via soluble Bax related apoptotic factors.
3.In-vitro studies with primary astrocytic and neuronal and other non neuronal cultures using immunocytochemistry,
morphometric analysis.
Krystle Frahm
• Leyssen, M., Ayaz, D., Hebert, S. S., Reeve, S., De Strooper, B., & Hassan, B. A.
(2005). Amyloid precursor protein promotes post-developmental neurite arborization
in the Drosophila brain. European Molecular Biology Organization, 24(16), 29442955.
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This paper is significant because it challenges previous findings and provides
further insight into the effects of amyloid precursor protein in the brain. This paper
found that amyloid precursor proteins may play a role in axonal outgrowth.
Drosophila brains were stained with an APPL antibody for image collection and
analyzed for axonal arboration. Rating: 3.
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• Masuoka, D. T., Jonsson, G., & Finch, C. E. (1979). Aging and unusual
catecholamine-containing structure in the mouse brain. Brain Research, 169(2), 335341.
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This paper is significant because it examines differences in the brain due to
aging. This article discovered unusual levels of catecholamine accumulation
indicating an association with nerve axons. Using the Falck-Hillarp histochemical
fluorescence technique to examine differences, the authors found a disparity in the
presence of catecholamine in mouse brains. Rating: 6
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Alex Martinez
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1-Methyl-4-phenylpyridinium induces synaptic dysfunction through a pathway involving
caspase and PKCdelta enzymatic activities. Proc Natl Acad Sci U S A. 2007 Feb
13;104(7):2437-41
This paper reports how “dying back” patterns of neurodegeneration may be due to an
alteration on fast axonal transport that is mediated by the activation of caspase-3 and protein
kinase C δ. The investigators in this study demonstrated that fast axonal transport was altered
by the toxin MPP+, which resulted in increased retrograde transport and decreased
anterograde mediated transport. Their explanation for this observation was that MPP+
induced the activation of caspase-3, which in turn activated PKC and thus elucidating the
“dying back” pattern of neuronal cell death by disrupting microtubule mediated transport.
This paper provides insight into the mechanism of cell death of MPP+.
Impairment of microtubule system increases alpha-synuclein aggregation and toxicity.
Biochem Biophys Res Commun. 2008 Jan 25;365(4):628-35.
In the present study, it was reported that the disruption of microtubule assembly could
stimulate the aggregation of alpha-synuclein, which is a hallmark of many neurodegenerative
diseases. Using S. cerevisiae as a model system, it was demonstrated that disruption of
microtubule assembly by treating with benomyl or by deleting necessary assembly genes,
increased alpha-synuclein aggregation and increased cellular toxicity. This report
demonstrates how the disruption of the microtubule system could prove to be toxic to the cell
by enhancing alpha-synuclein aggregation and cell death.
Paulino Gonzalez III
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Jones LG, Prins J, Park S, Walton JP, Luebke AE, Lurie DI.
Lead exposure during development results in increased neurofilament phosphorylation, neuritic beading,
and temporal processing deficits within the murine auditory brainstem.
J Comp Neurol. 2008 Feb 20;506(6):1003-17.
PMID: 18085597 [PubMed - in process]
This study is important because it shows risk factors associated with exposure to low and high
levels of lead in mice during gestation and 21 days postnatal. It was determined, that exposure the
lead during these developmental stages showed neuritic beading in immunolabeled axons, suggesting
that Lead exposure also impairs axonal transport. This reveals no significant loss in peripheral function
but does show impairments in brainstem conduction time and temporal processing within the brain stem.
This provides evidence to conclude that Pb exposure during development alters axonal structure and
function within brainstem auditory nuclei.
Rating: 9
Pan T, Kondo S, Le W, Jankovic J.
The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease.
Brain. 2008 Jan 10; [Epub ahead of print]
PMID: 18187492 [PubMed - as supplied by publisher]
This study is important because it study’s the role of the autophagy-lysosome pathway (ALP) and
tries to identify its link with neurodegenerative disorders. It was understood that mutations of alphasynucleins and non- mutant alpha-synucleins are strongly associated with Parkinson’s disease. This
study examined how mutant alpha-synucleins inhibit ALP function by tightly binding to the receptor on
the lysosomal membrane. This provides further evidence regarding the role of ALP and its possible
therapeutic potential through ALP enhancement.
Rating: 6
Alexandra Estela Soto-Pina
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First Paper: (4.8 factor)
Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, Young AB, Abagyan R, Feany MB, Hyman BT,
Kazantsev AG.
Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease.
Science. 2007 Jul 27;317(5837):516-9. Epub 2007 Jun 21.
PMID: 17588900 [PubMed - indexed for MEDLINE]
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Title: Sirtuin 2 (SIRT2) Inhibitors Rescue -Synuclein-Mediated Toxicity in Models of Parkinson's Disease
Significance: alpha synuclein is a protein expressed in substantia nigra. The accumulation of this protein results in the formation of insoluble fibrils in Parkinson’s disease (PD). Alpha
synclein toxicity is reversed by the deacetylase SIRT 2.
Discovery: This study reveals that SIRT 2 is a putative therapeutic target for PD. SIRT2 activity is reduced by pharmacological agents (AGK2) or RNAi.
How did they discover it?
1. Deacetylation biochemical assay H4 cell transfected with alpha syncluein and SIRT 2 and 3 RNAi’s: to show activity of SIRT2 over alpha synuclein
2. SIRT 2 enzymatic profile and dose-response curve to identify AGK2 (the inhibitor of SIR2).
3. Validation of AGK2 activity on SIRT 2 by immunoblotting
4. Activity of SIRT 2 inhibitors in Drosophila midbrain cultures: immunocytochemistry for MAP2 and TH.
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Second Paper (6.9 factor)
Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S.
Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death.
Nature. 2004 Oct 14;431(7010):805-10.
PMID: 15483602 [PubMed - indexed for MEDLINE]
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Title: Inclusion bodies formation reduces levels of mutant huntingtin and the risk of neuronal death.
Significance: polyglutamine (poly Q) expanded huntingtin is present in inclusion bodies characteristic of Huntington’s disease. Such disorder results from the genetically programmed
degeneration of brain cells. Inclusion bodies are a pathological feature of Huntington’s disease; however, in this paper they are presented as a cell survival alternative mechanism.
Relevant Discoveries:
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Specific length of poly Q species dictates toxicity. Specifically poly Q 47 is a marker for lifespan prediction.
Inclusion body incidence starts with the uptake of diffuse huntingtin toxic species.
Neurons with inclusion bodies present an optimal survival time to be detected.
How did they discover it?
They used GFP tagged huntingtin to determine inclusion body incidence in striatal neurons. They used a potent fluorescent microscopy system to detect fractions of transfected neurons as
well as the formation of aggregates. The neuronal counts were performed to estimate survival and risk of death.
Peter Samuel Campos
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Breysse N, Carlsson T, Winkler C, Björklund A, Kirik D. (2007). The functional impact of the intrastriatal dopamine
neuron grafts in parkinsonian rats is reduced with advancing disease. Journal of Neuroscience, May 30 27(22):5849-56.
10.0
Studies using nigrostriatal dopamine lesions suggest that good functional outcome can be obtained in animals with
limited dopaminergic denervation outside the striatal area innervated by a transplanted mesencephalic graft. However,
animals with complete lesions of the ascending dopamine projection system showed poor motor improvement, showing
that the amount of dopamine denervation in regions outside a graft-innervated area is a factor for significant effects of
dopamine cell replacement. The current study designed an experiment to directly test whether the functional impact of
intrastriatal ventral mesencephalon grafts could be compromised by late-stage loss of dopamine innervation in areas not
innervated by grafts, first establishing that multideposit grafts would provide widespread dopaminergic fiber innervation
to the caudate-putamen and improve motor behavior, then examining whether extension of the lesion to damage the
remaining host dopamine projections would compromise the functional efficacy of the grafts. This article is significant
because it brings to light that poor clinical outcomes following transplants may be due to dopaminergic degeneration of
areas outside the graft-innervated regions, as well as beneficial effects initially seen in patients could diminish if the
degeneration of host extrastriatal dopamine projections increases with advancing disease.
Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ. (2007). 'Rejuvenation' protects
neurons in mouse models of Parkinson's disease. Nature, Jun 28 447(7148):1081-6.
10.0
Reliance of dopamine neurons of the substantia nigra pars compacta on L-type Cav1.3 Ca2+ channels to drive their
maintained rhythmic pacemaking, which increases with age, renders them vulnerable to stressors thought to contribute
to disease progression. Blocking Cav1.3 Ca2+ channels in adult neurons induces a reversion to the juvenile form of
pacemaking, utilizing hyperpolarization-activated and cyclic nucleotide gated cation channels, a Ca2+ -independent
mechanism used early in life that remains latent into adulthood. Since this “rejuvenation” can be brought on by
treatment with isradipine, a drug currently used for the treatment of hypertension and stroke, a new neuroprotective use
for a common drug may be implemented. Diminishing the vulnerability of substantia nigra pars compacta dopaminergic
neurons would not only decrease the incidence of Parkinson’s disease but also slow its progression.
Juan Esquivel
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Inflammation, demyelization,neurodegeneration, and neuroprotection in the
pathogenesis of mutliple sclerosis. Peterson, Lisa K., Fujinami, Robert S.
Journal Neuroimmunology 184 (2007): 37-44
This paper examines the interconnections of inflammation and neurodegeneration in multiple
sclerosis. Though demyelization has been the main focus of multiple sclerosis research, there
may exist a relationship whereby inflammation and neurodegeneration may play a role in
multiple sclerosis either independently or in conjunction based upon various animal models
of multiple sclerosis. In addition, inflammation may protect against neurodegeneration.
Therefore, it remains to be seen if the course of multiple sclerosis is more complicated than
originally believed.
FACTOR: 6
Sodium channels and multiple sclerosis: Role in symptom production, damage and
therapy. Smith, Kenneth J.
Brain Pathology 2007 Apr;17(2):230-42.
This paper explores the contribution of sodium channels as a possible role in multiple
sclerosis. The mechanism by which affected sodium channels may contribute to multiple
sclerosis is examined as are some plausible immunological conditions affecting the sodium
channels. The authors not only investigated the proposed mechanism; however, different
types of sodium channels may expose a neuron to axonal damage than others, namely Nav1.6
sodium channels. Though therapeutic treatments in animal models have shown to provide
axonal protection from affected sodium channels, it still remains to be seen whether this
mode of treatment can be expanded to clinical trials.
FACTOR: 6
Lyn Marie Apa
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I chose two papers that address the effects of serotonin disruption on axonal transport. This coincides
with my current research involving changes in serotonin as a result of diet, and the implications of these
changes on antidepressant efficacy.
Comments on papers:
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Proteomic analysis of rat cortical neurons after fluoxetine (FLUX) treatment
The purpose of this paper was to better understand the mechanism of action of antidepressants, especially
in explaining the latency period between ingestion of SSRI’s and their clinical effects. This article was
unique in that it did not simply look at levels of neurotransmitters, but investigated other mechanisms of
action that have not been studied in depth. Interestingly, this research suggests that one way in which
fluoxetine exerts its long-term effects is by altering levels of proteins involved in axonal transport
(CypA, GRP78, etc). Although I am not an expert in the methods that they used for this particular study,
it appears these findings suggest a new approach to determining the mechanisms by which FLUX acts,
and could spur researchers to take a new approach to improving FLUX’s efficacy.
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Long-Term Impairment of Anterograde Axonal Transport Along Fiber Projections Originating in
the Rostral Raphe Nuclei After Treatment With Fenfluramine or
Methylenedioxymethamphetamine (MDMA)
Studies have suggested that both MDMA (a drug of abuse) and Fenfluramine (an anti-obesity drug
currently withdrawn from the market) work by increasing levels of serotonin in the brain. This study is
important because it suggests that such increases in neurotransmitter could be detrimental to axonal
transport, both in short- and long- term studies. These particular drugs were studied because they are
amphetamine substitutes, which are many times considered “safe” by doctors and “less dangerous” than
amphetamines by drug abusers. Thus, the findings that these substitutes can actually cause long-term
axonal transport impairment is pertinent information for drug abusers and those who prescribe and/or
consume prescribed medications which work by increasing serotonin levels.
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David Reese McKay
NATURE METHODS | VOL.4 NO.7 | JULY 2007 |
Imaging axonal transport of mitochondria in vivo
Thomas Misgeld, Martin Kerschensteiner, Florence M Bareyre, Robert W Burgess &
Jeff W Lichtman
Rating: 2
This article reports imaging of mouse mitochondria in vivo and in acute explants, which
provides a means to assess mitochondrial dynamics and distributions often seen in cell
cultures, but also active transport in normal and transected axons. Imaged mitochondria were
categorized as immobile, retrograde or anterograde, and corresponding rates for each axon
correlated, however, axonal cross section did not correlate with the number of mitochondria
moving in an axon. Mitochondrial reaction to axonal transection included an immediate drop
in anterograde rate that rebounded to 80% above the normal rate by 12 hours, accompanied by
a stable retrograde rate that persisted for 6 hours after transection and was interpreted as
evidence of an energy substrate in the distal ends of dendrites. Further, the cut end of an axon
was covered with axonal sprouts and populated with mitochondria within a week, while the
distal end deteriorated. Such in vivo imaging of axonal transport will be a pillar in the
mechanistic understanding of neurological dysfunction.
Proc. Nat. Acad. Sci. USA
Vol. 69, No. 3, pp. 620-623, March 1972
Neuronal Dynamics and Axonal Flow, V. The
Semisolid State of the Moving Axonal Column
PAUL A. WEISS
Rating: 3
This article proposes a mechanically plausible description of axonal transport, given the data
available in the late 1960s and early 1970s. While modern methods will not utilize such crude
physical descriptions, an understanding of the progression of science - especially with respect
to an early model or big picture theory – can be of high qualitative value to the student.