Differentiating between axonal damage and demyelination in healthy aging by combining diffusion-tensor imaging and diffusion-weighted spectroscopy in the human corpus callosum at 7 T

Branzoli, Francesca; Ercan, Ece; Valabrègue, Romain; Wood, Emily T.; Buijs, Mathijs; Webb, Andrew; Ronen, Itamar

doi:10.1016/j.neurobiolaging.2016.07.022

Cited by 27 publications

(25 citation statements)

References 56 publications

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“…Our findings are consistent with those reported by Hikishima et al using a marmoset model treated with MPTP [24]. The increased ADC value indicated a significant increase in the radial diffusivity of water molecules within the nigrostriatal fibres, suggesting that demyelination occurs [25–28]. The LFB staining confirmed that demyelination occurred in the TaClo-treated group, but not in the control group consistent with the DTI results.…”

Section: Discussionsupporting

confidence: 92%

1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Induces the Apoptosis of Dopaminergic Neurons via Oxidative Stress and Neuroinflammation

Yang

Pang

Liu

et al. 2019

Oxidative Medicine and Cellular Longevity

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Several in vitro studies have revealed the neurotoxicity of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo). However, the underlying mechanism has not been completely elucidated, particularly in vivo. This study was designed to study the neurotoxicity of TaClo in vivo by stereotactically injecting TaClo into the striatum of Wistar rats. After the TaClo injections, rats were subjected to an open field test, and their distance travelled and tracks showed decreasing trends over time. The results of liquid chromatography-mass spectrometry analysis showed that the motor dysfunction of the TaClo-treated rats was accompanied by reduced dopamine levels in the striatum. Based on the diffusion tensor imaging data, the apparent diffusion coefficient of the nigrostriatal pathway was significantly increased, and subsequent histological staining revealed the demyelination of nigrostriatal fibres after the TaClo treatment. TaClo induced a loss of tyrosine hydroxylase-positive cells in the substantia nigra compacta. Regarding the underlying mechanism, TaClo caused oxidative stress in the nigrostriatal system by increasing the production of reactive oxygen species and reducing the mitochondria membrane potential. Meanwhile, the elevated expression of Iba-1, TNF-α, IL-6, Cox-2, and iNOS indicated microglial activation and a strong innate immune response in the nigrostriatal system. In addition, activated caspase-3 levels were increased. Thus, both mitochondrial impairments and the innate immune response are involved in TaClo-induced neurotoxicity.

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Section: Discussionsupporting

confidence: 92%

1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Induces the Apoptosis of Dopaminergic Neurons via Oxidative Stress and Neuroinflammation

Yang

Pang

Liu

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…One of the major discoveries involving G93A-SOD1 mice is that ALS is not cell specific, which means that glial cells surrounding motor neurons are probably involved in the mechanisms leading to the selective death of motor neurons, 70 and specific differences have been described between axonal damage and reduction in myelin content using DTI. 41,71,72 In particular, our study aimed to unveil the role of RD and myelin degeneration in ALS at earlier stages of the disease. 70,73 Consistent with previous reports of oligodendrocyte impairments in ALS, 73,74 our investigations determined a presymptomatic increase in RD associated with an early reduction in MBP in YFP,G93A-SOD1 mice (Figure 4a, b).…”

Section: Discussionsupporting

confidence: 91%

“…One of the major discoveries involving G93A‐SOD1 mice is that ALS is not cell specific, which means that glial cells surrounding motor neurons are probably involved in the mechanisms leading to the selective death of motor neurons, and specific differences have been described between axonal damage and reduction in myelin content using DTI . In particular, our study aimed to unveil the role of RD and myelin degeneration in ALS at earlier stages of the disease .…”

Section: Discussionmentioning

confidence: 99%

In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model of amyotrophic lateral sclerosis

Gatto

Gao

2018

NMR in Biomedicine

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Diffusion magnetic resonance imaging (MRI) exhibits contrast that identifies macro- and microstructural changes in neurodegenerative diseases. Previous studies have shown that MR diffusion tensor imaging (DTI) can observe changes in spinal cord white matter in animals and humans affected with symptomatic amyotrophic lateral sclerosis (ALS). The goal of this preclinical work was to investigate the sensitivity of DTI for the detection of signs of tissue damage before symptoms appear. High-field MRI data were acquired using a 9.4-T animal scanner to examine the spinal cord of an ALS mouse model at pre- and post-symptomatic stages (days 80 and 120, respectively). The MRI results were validated using yellow fluorescent protein (YFP) via optical microscopy of spinal cord tissue slices collected from the YFP,G93A-SOD1 mouse strain. DTI maps of diffusion-weighted imaging (DWI) signal intensity, mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) were computed for axial slices of the lumbar region of the spinal cord. Significant changes were observed in FA (6.7% decrease, p < 0.01), AD (19.5% decrease, p < 0.01) and RD (16.1% increase, p < 0.001) at postnatal day 80 (P80). These differences were correlated with changes in axonal fluorescence intensity and membrane cellular markers. This study demonstrates the value of DTI as a potential tool to detect the underlying pathological progression associated with ALS, and may accelerate the discovery of therapeutic strategies for patients with this disease.

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“…Hampshire, Chamberlain, Monti, Duncan, and Owen () reported that the role of rIFG is primarily in the provision of attention to relevant cues, and is recruited to the same extent regardless of whether cue detection is followed by either successful or unsuccessful inhibition. Although our findings pertaining to age‐related compensation could be interpreted as reflecting normal age‐related changes in rIFG, it is unlikely to be the case given that demyelination does not occur until later in life, and thus would not yet have affected our sample (Branzoli et al., ; Peters, , ). This could provide an interesting line of investigation for future studies to consider whether rIFG delivers the same compensatory mechanism in proactive inhibition after normal dopamine loss in healthy ageing, thus contributing further evidence to the topography of the effect we have reported here.…”

Section: Discussionmentioning

confidence: 82%

Polymorphisms in dopaminergic genes predict proactive processes of response inhibition

Beu

Burns

Baetu

2019

Eur J of Neuroscience

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The ability to inhibit a prepared emotional or motor action is difficult but critical to everyday functioning. It is well‐established that response inhibition relies on the dopaminergic system in the basal ganglia. However, response inhibition is often measured imprecisely due to a process which slows our responses and increases subsequent inhibition success known as proactive inhibition. As the role of the dopamine system in proactive inhibition is unclear, we investigated the contribution of dopaminergic genes to proactive inhibition. We operationalised proactive inhibition as slower responses after failures to inhibit a response in a Go/No‐Go paradigm and investigated its relationship to rs686/A at DRD1 (associated with increased gene expression) and rs1800497/T at DRD2 (associated with reduced D2 receptor availability). Even though our sample (N = 264) was relatively young (18–40 years), we found that proactive inhibition improves the ability to withhold erroneous responses in older participants (p = 0.002) and those with lower fluid intelligence scores (p < 0.001), indicating that proactive inhibition is likely a naturally occurring compensatory mechanism. Critically, we found that a polygenic risk score consisting of the number of rs686 A and rs1800497 T alleles predicts higher engagement of proactive inhibition (p = 0.040), even after controlling for age (p = 0.011). Furthermore, age seemed to magnify these genetic effects (p < 0.001). This suggests that the extent to which proactive inhibition is engaged depends on increased dopamine D1 and decreased D2 neurotransmission. These results provide important considerations for future work investigating disorders of the dopaminergic system.

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Differentiating between axonal damage and demyelination in healthy aging by combining diffusion-tensor imaging and diffusion-weighted spectroscopy in the human corpus callosum at 7 T

Cited by 27 publications

References 56 publications

1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Induces the Apoptosis of Dopaminergic Neurons via Oxidative Stress and Neuroinflammation

1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Induces the Apoptosis of Dopaminergic Neurons via Oxidative Stress and Neuroinflammation

In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model of amyotrophic lateral sclerosis

Polymorphisms in dopaminergic genes predict proactive processes of response inhibition

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