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

Abstract

Diffusion-tensor imaging and single voxel diffusion-weighted magnetic resonance spectroscopy were used at 7T to explore in vivo age-related microstructural changes in the corpus callosum. Sixteen healthy elderly (age range 60-71 years) and 13 healthy younger controls (age range 23-32 years) were included in the study. In healthy elderly, we found lower water fractional anisotropy and higher water mean diffusivity and radial diffusivity in the corpus callosum, indicating the onset of demyelination processes with healthy aging. These changes were not associated with a concomitant significant difference in the cytosolic diffusivity of the intra-axonal metabolite N-acetylaspartate (p = 0.12), the latter representing a pure measure of intra-axonal integrity. It was concluded that the possible intra-axonal changes associated with normal aging processes are below the detection level of diffusion-weighted magnetic resonance spectroscopy in our experiment (e.g., smaller than 10%) in the age range investigated. Lower axial diffusivity of total creatine was observed in the elderly group (p = 0.058), possibly linked to a dysfunction in the energy metabolism associated with a deficit in myelin synthesis.

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

“…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.…”

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

“…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).…”

“…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 .…”

Polymorphisms in dopaminergic genes predict proactive processes of response inhibition

“…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.…”