DMSO modulates CNS function in a preclinical Alzheimer's disease model

Penazzi, Lorène; Lorengel, Julia; Sündermann, Frederik; Golovyashkina, Nataliya; Marre, Stefan; Mathis, Chantal; Lewejohann, Lars; Brandt, Roland; Bakota, Lidia

doi:10.1016/j.neuropharm.2016.10.020

Cited by 36 publications

(37 citation statements)

References 60 publications

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“…This shows that R-MO might have weak cognitive enhancing effects and it suggests molecular mechanisms that might be involved. Spatial memory modulating effects of DMSO have been reported in previous studies, ranging from enhancing effects at low doses [32,33] to impairing effects at high doses [34]. We could observe at least an acutely impairing effect of DMSO on spatial memory and synaptic plasticity, possible long lasting effects, however remain to be investigated.…”

Section: Discussionsupporting

confidence: 52%

R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity

et al. 2017

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Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP). Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO) or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT), and its phosphorylated form (ph-DAT) in DG tissue 4 h after LTP induction were quantified by western blot analysis. Monoamine reuptake and release assays were performed by using transfected HEK-293 cells. Possible neurotoxic side effects on general behaviour were also studied. R-MO at both doses significantly enhanced spatial reference memory during the last training session and during memory retrieval compared to DMSO vehicle but not when compared to saline treated rats. Similarly, R-MO rescues DG-LTP from impairing effects of DMSO. DMSO reduced memory performance and LTP magnitude when compared to saline treated groups. The synaptic DR1 levels in R-MO groups were significantly decreased compared to DMSO group but were comparable with saline treated animals. We found no effect of R-MO in neurotoxicity tests. Thus, our results support the notion that LTP-like synaptic plasticity processes could be one of the factors contributing to the cognitive enhancing effects of spatial memory traces. D1R may play an important regulatory role in these processes.

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Section: Discussionsupporting

confidence: 52%

R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity

et al. 2017

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“…Therefore, there existed < 1% (< 0.01 mL/kg body weight) DMSO in the injected EpoB solution. In a latest report, DMSO treatment (1% in drinking water, maintained for 34 days) increased spine density on neurons in a region‐specific manner and displayed behavior influence in Alzheimer's disease model (Penazzi et al ., ). Our dosage is lower than that adopted in the paper.…”

Section: Discussionmentioning

confidence: 97%

Microtubule stabilization promoted axonal regeneration and functional recovery after spinal root avulsion

2017

Eur J of Neuroscience

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A spinal root avulsion injury disconnects spinal roots with the spinal cord. The rampant motoneuron death, inhibitory CNS/PNS transitional zone (TZ) for axonal regrowth and limited regeneration speed together lead to motor dysfunction. Microtubules rearrange to assemble a new growth cone and disorganized microtubules underline regeneration failure. It has been shown that microtubule-stabilizing drug, Epothilone B, enhanced axonal regeneration and attenuated fibrotic scaring after spinal cord injury. Here, we are reporting that after spinal root avulsion+ re-implantation in adult rats, EpoB treatment improved motor functional recovery and potentiated electrical responses of motor units. It facilitated axons to cross the TZ and promoted more and bigger axons in the peripheral nerve. Neuromuscular junctions were reformed with better preserved postsynaptic structure, and muscle atrophy was prevented by EpoB administration. Our study showed that EpoB was a promising therapy for promoting axonal regeneration after peripheral nerve injury.

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“…Previous studies reported that SalB is an inactive metabolite of the KOR-selective agonist Salvinorin A [26, 28]. However, DMSO has been shown to be able to modulate central nervous system function [29]. To estimate this effect, we used the sham group that didn’t express designer receptors that could be affected by SalB/DMSO.…”

Section: Methodsmentioning

confidence: 99%

Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity

Peeters

Hinz

Detrez

et al. 2019

Preprint

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29The anterior cingulate area (ACA) is an integral part of the prefrontal cortex in mice and has been 30 implicated in several cognitive functions. Previous anatomical and functional imaging studies 31 demonstrated that the ACA is highly interconnected with numerous brain regions acting as a hub region 32 in functional networks. However, the importance of the ACA in regulating functional network activity and 33 connectivity remains to be elucidated. Recently developed neuromodulatory techniques, such as Designer 34Receptors Exclusively Activated by Designer Drugs (DREADDs) allow for precise control of neuronal 35 activity. In this study, we used an inhibitory kappa-opioid receptor DREADDs (KORD) to temporally inhibit 36 neuronal firing in the right ACA of mice and assessed functional network activity and connectivity using 37 non-invasive functional MRI. We demonstrated that KORD-induced inhibition of the right ACA induced 38 blood oxygenation-level dependent (BOLD) signal decreases and increases in connected brain regions 39 throughout of hemispheres. Furthermore, these modulations in neuronal activity were associated with 40 decreased intra-and interhemispheric functional connectivity. These results demonstrate that the 41 combination of the DREADD technology and non-invasive functional imaging methods is a valuable tool 42 for unraveling the underlying mechanisms of network function and dysfunction. 43 44 45 Receptors Exclusively Activated by Designer Drugs (DREADDs), which are engineered receptors for 63 targeted enhancement or silencing of neurons upon binding of an otherwise inert ligand. The combination 64 of chemogenetics and non-invasive neuroimaging methods, such as functional magnetic resonance 65 imaging (fMRI), allows direct evaluation of DREADD-induced changes in neuronal firing on large-scale 66 neuronal activity and FC. As such, Giorgi et al. were able to causally link the chemogenetic activation of 67serotonergic neurons with neuronal activity increases in cortical and subcortical brain areas, measured by 68 relative cerebral blood volume increases [23]. Furthermore, other studies also used blood-oxygenation-69

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DMSO modulates CNS function in a preclinical Alzheimer's disease model

Cited by 36 publications

References 60 publications

R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity

R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity

Microtubule stabilization promoted axonal regeneration and functional recovery after spinal root avulsion

Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity

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