Isoflurane anesthesia precipitates tauopathy and upper airways dysfunction in pre-symptomatic Tau.P301L mice: Possible implication for neurodegenerative diseases

Menuet, Clément; Borghgraef, Peter; Voituron, Nicolas; Gestreau, Christian; Gielis, Lies; Devijver, Herman; Dutschmann, Mathias; Leuven, Fred Van; Hilaire, Gérard

doi:10.1016/j.nbd.2012.01.012

Cited by 20 publications

(20 citation statements)

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“…However, the mechanisms involved in mediating this effect and the long-term neuropathological and functional sequelae stemming from this aberrant hyperphosphorylation have yet to be fully elucidated. Furthermore, as previous studies with isoflurane have not observed such negative effects on tau pathology in a normothermic setting (Planel et al, 2009; Menuet et al, 2012), these recent studies by Le Freche et al and Tang et al, which indeed demonstrate a pathological change in tau following normothermic volatile anesthetic exposure, strongly suggest that whether an anesthesia-induced detrimental effect on tau pathology will become manifest is possibly dependent on several factors: the anesthetic exposure paradigm, mouse strain and genotype, tau phenotype, and the actual time point at which the animal is examined for tau pathology.…”

Section: Anesthesia-induced Tau Pathology and Normothermiamentioning

confidence: 54%

“…Interestingly, these investigators observed in 4 month old Tau P301L mice that a single exposure to 4h 1MAC isoflurane, under hypothermic conditions, resulted in the premature development of upper airway defects, which are normally observed in this mouse tauopathy model at later stages of life. Indeed, measurements of upper airway function revealed that the administration of isoflurane in a hypothermic environment resulted in the development of respiratory compromise at 4 months, which was comparable to the respiratory pathology typically observed in these mice at 8 months (Menuet et al, 2012). However, the administration of a similar dose of isoflurane to these Tau P301L mice with temperature control prevented the development of the ventilation abnormalities.…”

Section: Anesthesia-induced Hypothermia and The Development Of Tau Pamentioning

confidence: 69%

“…have reported increased AT8 staining and tauopathy in several brainstem regions, including the nucleus ambiguus and Kolliker-Fuse nuclei, at 7 days post-exposure (Menuet et al, 2012). This mouse model of tauopathy has been previously shown to develop cognitive deficits as well as vocalization and respiratory abnormalities, the latter condition ultimately leading to premature death (Terwel et al, 2005; Dutschmann et al, 2010; Menuet et al, 2011b; Menuet et al, 2011a; Menuet et al, 2012). Moreover’, these transgenic mice develop evidence of tauopathy within the pontine Kolliker-Fuse nucleus (Dutschmann et al, 2010).…”

Section: Anesthesia-induced Hypothermia and The Development Of Tau Pamentioning

confidence: 99%

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Anesthesia and tau pathology

Whittington

Bretteville

Dickler

et al. 2013

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Alzheimer’s disease (AD) is the most common form of dementia and remains a growing worldwide health problem. As life expectancy continues to increase, the number of AD patients presenting for surgery and anesthesia will steadily rise. The etiology of sporadic AD is thought to be multifactorial, with environmental, biological and genetic factors interacting together to influence AD pathogenesis. Recent reports suggest that general anesthetics may be such a factor and may contribute to the development and exacerbation of this neurodegenerative disorder. Intra-neuronal neurofibrillary tangles (NFT), composed of hyperphosphorylated and aggregated tau protein are one of the main neuropathological hallmarks of AD. Tau pathology is important in AD as it correlates very well with cognitive dysfunction. Lately, several studies have begun to elucidate the mechanisms by which anesthetic exposure might affect the phosphorylation, aggregation and function of this microtubule-associated protein. Here, we specifically review the literature detailing the impact of anesthetic administration on aberrant tau hyperphosphorylation as well as the subsequent development of neurofibrillary pathology and degeneration.

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Section: Anesthesia-induced Tau Pathology and Normothermiamentioning

confidence: 54%

Section: Anesthesia-induced Hypothermia and The Development Of Tau Pamentioning

confidence: 69%

Section: Anesthesia-induced Hypothermia and The Development Of Tau Pamentioning

confidence: 99%

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Anesthesia and tau pathology

Whittington

Bretteville

Dickler

et al. 2013

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Importantly, performing experiments in awake, head-fixed animals eliminates the impact of anesthesia on response properties, resting calcium, and tau aggregation ( Fig. 1 A and B and Movie S1) (19).…”

mentioning

confidence: 99%

Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo

Kuchibhotla

Wegmann

Kopeikina

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

179

136

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Alzheimer's disease (AD) is pathologically characterized by the deposition of extracellular amyloid-β plaques and intracellular aggregation of tau protein in neurofibrillary tangles (NFTs) (1, 2). Progression of NFT pathology is closely correlated with both increased neurodegeneration and cognitive decline in AD (3) and other tauopathies, such as frontotemporal dementia (4,5). The assumption that mislocalization of tau into the somatodendritic compartment (6) and accumulation of fibrillar aggregates in NFTs mediates neurodegeneration underlies most current therapeutic strategies aimed at preventing NFT formation or disrupting existing NFTs (7,8). Although several disease-associated mutations cause both aggregation of tau and neurodegeneration, whether NFTs per se contribute to neuronal and network dysfunction in vivo is unknown (9). Here we used awake in vivo two-photon calcium imaging to monitor neuronal function in adult rTg4510 mice that overexpress a human mutant form of tau (P301L) and develop cortical NFTs by the age of 7-8 mo (10). Unexpectedly, NFT-bearing neurons in the visual cortex appeared to be completely functionally intact, to be capable of integrating dendritic inputs and effectively encoding orientation and direction selectivity, and to have a stable baseline resting calcium level. These results suggest a reevaluation of the common assumption that insoluble tau aggregates are sufficient to disrupt neuronal function.paired helical filaments | tau pathology | neuronal networks N eurofibrillary tangles (NFTs) containing aggregated tau protein (1) have long been considered key players in the progressive neural dysfunction and neurodegeneration observed in Alzheimer's disease (AD) (2, 3) and other tauopathies (4, 5). It is commonly assumed that NFT-bearing neurons exhibit deficits in synaptic integration and eventually lead to neurodegeneration (11,12). However, the actual functional properties of NFT-bearing neurons in intact neural circuits have not been explored previously (13). We addressed this question directly using awake in vivo two-photon calcium imaging in a mouse model of NFT formation (rTg4510) by applying recently developed imaging approaches allowing for single-neuron-level and population-level assessment of neural activity in awake mice (14). Because two-photon calcium imaging allows for measurement of response properties in many neurons simultaneously, we were able to directly isolate the impact of NFT deposition in a neuronal microcircuit by evaluating population-level network dynamics and, more specifically, by differentiating the function of individual NFT-bearing and neighboring non-NFT-bearing neurons.To assess the functional properties of neurons in the visual cortex, we used a genetically encoded ratiometric calcium indicator, yellow cameleon 3.6 (YC3.6), packaged in an adenoassociated viral vector (15,16). To assess functional responses, we exploited the well-characterized functional architecture of visual cortex whereby neurons in mouse visual cortex modulate their activity d...

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“…Indeed, individuals with DS have been reported to respond differently to general anesthesia (67), so it is not unlikely that this also is true for the DS mouse models. Additionally, it has been reported that isoflurane exposure may lead to neurotoxicity and adverse effects in other mouse models, such as mouse models of Aβ deposition and tauopathy (68, 69). Another limitation is that our study lacks a direct correlation with behavior or morphology data.…”

Section: Discussionmentioning

confidence: 99%

Evidence of altered age-related brain cytoarchitecture in mouse models of down syndrome: a diffusional kurtosis imaging study

Nie¹,

Hamlett²,

Granholm³

et al. 2015

Magnetic Resonance Imaging

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Mouse models of Down syndrome (DS) exhibit abnormal brain developmental and neurodegenerative changes similar to those seen in individuals with DS. Although DS mice have been well characterized cognitively and morphologically there are no prior reports utilizing diffusion MRI. In this study we investigated the ability of diffusional kurtosis imaging (DKI) to detect the progressive developmental and neurodegenerative changes in the Ts65Dn (TS) DS mouse model. TS mice displayed higher diffusional kurtosis (DK) in the frontal cortex (FC) compared to normal mice at 2 months of age. At 5 months of age, TS mice had lower radial kurtosis in the striatum (ST), which persisted in the 8-month-old mice. The TS mice exhibited lower DK metrics values in the dorsal hippocampus (HD) at all ages, and the group difference in this region was larger at 8-months. Regression analysis showed that normal mice had a significant age-related increase in DK metrics in FC, ST and HD. On the contrary, the TS mice lacked significant age-related increase in DK metrics in FC and ST. Although preliminary, these results demonstrate that DK metrics can detect TS brain developmental and neurodegenerative abnormalities.

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Isoflurane anesthesia precipitates tauopathy and upper airways dysfunction in pre-symptomatic Tau.P301L mice: Possible implication for neurodegenerative diseases

Cited by 20 publications

References 63 publications

Anesthesia and tau pathology

Anesthesia and tau pathology

Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo

Evidence of altered age-related brain cytoarchitecture in mouse models of down syndrome: a diffusional kurtosis imaging study

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