Changes in microtubule turnover accompany synaptic plasticity and memory formation in response to contextual fear conditioning in mice

Fanara, Patrizia; Husted, Kristofor H.; Selle, K.; Wong, Po-yin Anne; Banerjee, Jayee; Brandt, Roland; Hellerstein, Marc K.

doi:10.1016/j.neuroscience.2010.03.031

Cited by 70 publications

(81 citation statements)

References 38 publications

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“…Altered MT dynamics in tau transgenic mice MT dynamics can be measured in vivo using a novel deuterium labeling procedure (Fanara et al, 2004(Fanara et al, , 2007(Fanara et al, , 2010. Following labeling of body fluids with 2 H 2 O, deuterium becomes incorporated into nonessential amino acids and then into newly synthesized proteins.…”

Section: Resultsmentioning

confidence: 99%

“…Beads were washed with 80 mM PIPES, pH 6.8, plus 1 mM MgCl 2 , followed by elution with 80 mM PIPES, pH 6.8, 1 mM MgCl 2 , and 1 M sodium chloride. The remaining unbound MTs have previously been shown to be largely cold stable MTs (Fanara et al, 2010).…”

Section: Methodsmentioning

confidence: 99%

“…This assay was performed as described previously (Fanara et al, 2010) with minor modifications. In brief, mice received an intraperitoneal bolus of 30 -35 ml/kg 2 H 2 O (99.9 mol%) in saline and were then maintained on 8% 2 H 2 O in drinking water for 24 h before being killed.…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analyses were performed as described previously (Fanara et al, 2007(Fanara et al, , 2010 using Tau5 to detect all forms of tau, ab5392 to detect MAP-2, and DM1A to detect ␣-tubulin (Sigma-Aldrich). Equal amounts of protein (BCA Protein Assay, Thermo Scientific) were loaded in each lane, and quantitation of ␣-tubulin was done using densitometry of film in the linear range.…”

Section: Methodsmentioning

confidence: 99%

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Hyperdynamic Microtubules, Cognitive Deficits, and Pathology Are Improved in Tau Transgenic Mice with Low Doses of the Microtubule-Stabilizing Agent BMS-241027

Barten¹,

Fanara²,

Andorfer³

et al. 2012

J. Neurosci.

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163

156

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Tau is a microtubule (MT)-stabilizing protein that is altered in Alzheimer's disease (AD) and other tauopathies. It is hypothesized that the hyperphosphorylated, conformationally altered, and multimeric forms of tau lead to a disruption of MT stability; however, direct evidence is lacking in vivo. In this study, an in vivo stable isotope-mass spectrometric technique was used to measure the turnover, or dynamicity, of MTs in brains of living animals. We demonstrated an age-dependent increase in MT dynamics in two different tau transgenic mouse models, 3xTg and rTg4510. MT hyperdynamicity was dependent on tau expression, since a reduction of transgene expression with doxycycline reversed the MT changes. Treatment of rTg4510 mice with the epothilone, BMS-241027, also restored MT dynamics to baseline levels. In addition, MT stabilization with BMS-241027 had beneficial effects on Morris water maze deficits, tau pathology, and neurodegeneration. Interestingly, pathological and functional benefits of BMS-241027 were observed at doses that only partially reversed MT hyperdynamicity. Together, these data suggest that tau-mediated loss of MT stability may contribute to disease progression and that very low doses of BMS-241027 may be useful in the treatment of AD and other tauopathies.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Hyperdynamic Microtubules, Cognitive Deficits, and Pathology Are Improved in Tau Transgenic Mice with Low Doses of the Microtubule-Stabilizing Agent BMS-241027

Barten¹,

Fanara²,

Andorfer³

et al. 2012

J. Neurosci.

Self Cite

163

156

View full text Add to dashboard Cite

show abstract

“…The reason why Aβ42 levels are decreased in CSF of these patients is believed to be caused by the impairment of the physiologic clearance mechanism above described. Major biological function of tau is to promote microtubule assembly and maintain the stability of the microtubules, play also crucial roles in signal transduction of neurons Fanara et al, 2010), and in neural plasticity mechanisms (Avila et al, 2004;Boekhoorn et al, 2006). In AD patients, where plasticity mechanisms are altered, t-Tau levels increase three-fold than the age-matched controls.…”

Section: Cerebrospinal Fluid Analysismentioning

confidence: 99%

Clinical Profile of Alzheimer’s Disease Non-Responder Patient

Martorana¹,

Semprini²,

Koch³

2011

Advanced Understanding of Neurodegenerative Diseases

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Analysis of Microtubule Dynamics Heterogeneity in Cell Culture

Serikbaeva

Tvorogova

Kauanova

et al. 2018

Cellular Heterogeneity

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Microtubules (MTs) are dynamic components of the cytoskeleton playing an important role in a large number of cell functions. Individual MTs in living cells undergo stochastic switching between alternate states of growth, shortening and attenuated phase, a phenomenon known as tempered dynamic instability. Dynamic instability of MTs is usually analyzed by labeling MTs with +TIPs, namely, EB proteins. Tracking of +TIP trajectories allows analyzing MT growth in cells with a different density of MTs. Numerous labs now use +TIP to track growing MTs in a variety of cell cultures. However, heterogeneity of MT dynamics is usually underestimated, and rather small sampling for the description of dynamic instability parameters is often used. The strategy described in this chapter is the method for repetitive quantitative analysis of MT growth rate within the same cell that allows minimization of the variation in MT dynamics measurement. We show that variability in MT dynamics within a cell when using repeated measurements is significantly less than between different cells in the same chamber. This approach allows better estimation of the heterogeneity of cells' responses to different treatments. To compare the effects of different MT inhibitors, the protocol using normalized values for MT dynamics and repetitive measurements for each cell is employed. This chapter provides detailed methods for analysis of MT dynamics in tissue cultures. We describe protocols for imaging MT dynamics by fluorescent microscopy, contrast enhancement technique, and MT dynamics analysis using triple color-coded display based on sequential subtraction analysis.

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Changes in microtubule turnover accompany synaptic plasticity and memory formation in response to contextual fear conditioning in mice

Cited by 70 publications

References 38 publications

Hyperdynamic Microtubules, Cognitive Deficits, and Pathology Are Improved in Tau Transgenic Mice with Low Doses of the Microtubule-Stabilizing Agent BMS-241027

Hyperdynamic Microtubules, Cognitive Deficits, and Pathology Are Improved in Tau Transgenic Mice with Low Doses of the Microtubule-Stabilizing Agent BMS-241027

Clinical Profile of Alzheimer’s Disease Non-Responder Patient

Analysis of Microtubule Dynamics Heterogeneity in Cell Culture

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