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Published on: August 14, 2019
Microstructural changes to the brain of mice after methamphetamine exposure as identified with diffusion tensor
Benjamin S McKenna1, Gregory G Brown1, Sarah Archibald1
1Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA.
Abstract:
Methamphetamine (METH) is an addictive psychostimulant inducing neurotoxicity. Human magnetic resonance imaging and diffusion tensor imaging (DTI) of METH-dependent participants find various structural abnormities. Animal studies demonstrate immunohistochemical changes in multiple cellular pathways after METH exposure. Here, we characterized the long-term effects of METH on brain microstructure in mice exposed to an escalating METH binge regimen using in vivo DTI, a methodology directly translatable across species. Results revealed four patterns of differential fractional anisotropy (FA) and mean diffusivity (MD) response when comparing METH-exposed (n=14) to saline-treated mice (n=13). Compared to the saline group, METH-exposed mice demonstrated: 1) decreased FA with no change in MD [corpus callosum (posterior forceps), internal capsule (left), thalamus (medial aspects), midbrain], 2) increased MD with no change in FA [posterior isocortical regions, caudate-putamen, hypothalamus, cerebral peduncle, internal capsule (right)], 3) increased FA with decreased MD [frontal isocortex, corpus callosum (genu)], and 4) increased FA with no change or increased MD [hippocampi, amygdala, lateral thalamus]. MD was negatively associated with calbindin-1 in hippocampi and positively with dopamine transporter in caudate-putamen. These findings highlight distributed and differential METH effects within the brain suggesting several distinct mechanisms. Such mechanisms likely change brain tissue differentially dependent upon neural location.
Insights
Long-term methamphetamine (METH) exposure causes distinct changes in brain microstructure. Diffusion tensor imaging (DTI) revealed varied effects on fractional anisotropy (FA) and mean diffusivity (MD) across brain regions in mice.
Area of Science:
- Neuroscience
- Neuroimaging
- Neurotoxicology
Background:
- Methamphetamine (METH) is a psychostimulant known for its addictive properties and neurotoxic effects.
- Previous studies in humans and animals have indicated structural and cellular abnormalities following METH exposure.
- Diffusion tensor imaging (DTI) is a valuable tool for assessing brain microstructure non-invasively.
Purpose of the Study:
- To characterize the long-term effects of METH on brain microstructure in mice.
- To investigate differential microstructural changes across various brain regions using in vivo DTI.
- To correlate microstructural changes with specific neurochemical markers.
Main Methods:
- Utilized an escalating METH binge regimen in mice.
- Employed in vivo diffusion tensor imaging (DTI) to assess brain microstructure.
- Analyzed fractional anisotropy (FA) and mean diffusivity (MD) values in specific brain regions.
- Correlated DTI metrics with immunohistochemical markers (calbindin-1, dopamine transporter).
Main Results:
- Identified four distinct patterns of microstructural changes (FA/MD alterations) in METH-exposed mice compared to controls.
- Observed region-specific effects, including decreased FA, increased MD, or combined changes in various brain areas like the corpus callosum, internal capsule, thalamus, and hippocampus.
- Found significant associations between mean diffusivity (MD) and calbindin-1 in the hippocampus and dopamine transporter in the caudate-putamen.
Conclusions:
- Long-term METH exposure induces distributed and differential microstructural alterations in the mouse brain.
- These findings suggest that METH affects neural tissue through several distinct mechanisms, varying by brain location.
- The study highlights the utility of in vivo DTI for detecting METH-induced neurotoxicity in a translatable manner.
