A nutrient combination designed to enhance synapse formation and function improves outcome in experimental spinal cord injury

Pallier, Patrick N.; Poddighe, Laura; Zbarsky, Virginia; Kostusiak, Milosz; Choudhury, Rasall; Hart, Thomas; Burguillos, Miguel Ángel; Musbahi, Omar; Groenendijk, Martine; Sijben, John; deWilde, Martijn C.; Quartu, Marina; Priestley, John V.; Michael‐Titus, Adina T.

doi:10.1016/j.nbd.2015.09.007

Cited by 22 publications

(41 citation statements)

References 68 publications

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“…The present results regarding the effectiveness of the extended dietary intervention (Diet2) in restoring functional connectivity in the rotenone model of PD are in line with previous observations in other models of either ongoing neurodegeneration (Jansen et al, 2013; Wiesmann et al, 2016) or acute neurotrauma (Pallier et al, 2015; Wiesmann et al, 2017). In these experiments Diet2 improved both neuronal connectivity and behavioral output, suggesting a broad applicability of this nutritional technology.…”

Section: Discussionsupporting

confidence: 91%

Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease

Perez‐Pardo

Jong

Broersen

et al. 2017

Front. Aging Neurosci.

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Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic nigrostriatal neurons, with reductions in the function and amount of dopaminergic synapses. Therefore, synapse loss and membrane-related pathology provide relevant targets for interventions in PD. We previously showed the beneficial preventive effects of a dietary intervention containing uridine and DHA, two precursors for membrane synthesis, in the intrastriatal rotenone model for PD. Here, we examined the therapeutic potential of the same dietary intervention on motor, cognitive, and gastrointestinal symptoms. In addition, we tested the effects of an extended nutritional formula based on the same precursors plus other nutrients that increase membrane phospholipid synthesis as well as prebiotic fibers. C57BL/6J mice received a unilateral rotenone injection in the striatum. Dietary interventions started 28 days after surgery, when motor-symptoms had developed. Readout parameters included behavioral tasks measuring motor function and spatial memory as well as intestinal function and histological examination of brain and gut to assess PD-like pathology. Our results show that rotenone-induced motor and non-motor problems were partially alleviated by the therapeutic dietary interventions providing uridine and DHA. The extended nutritional intervention containing both precursors and other nutrients that increase phospholipid synthesis as well as prebiotic fibers was more effective in normalizing rotenone-induced motor and non-motor abnormalities. The latter diet also restored striatal DAT levels, indicating its neurorestorative properties. This is the first study demonstrating beneficial effects of specific dietary interventions, given after full development of symptoms, on a broad spectrum of motor and non-motor symptoms in a mouse model for PD.

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Section: Discussionsupporting

confidence: 91%

Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease

Perez‐Pardo

Jong

Broersen

et al. 2017

Front. Aging Neurosci.

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“…In this context, it is relevant that DHA is the precursor of local anti-inflammatory autacoids, designated with the generic term of “docosanoids”, that are produced on demand and have been shown to act as negative regulators of inflammation processes otherwise becoming pathological [ 60 ]. Recent prophylactic and therapeutic approaches for cerebrovascular disease take into account the pathways of brain accretion and delivery of DHA [ 56 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Preventive Effects of Resveratrol on Endocannabinoid System and Synaptic Protein Modifications in Rat Cerebral Cortex Challenged by Bilateral Common Carotid Artery Occlusion and Reperfusion

Carta

Poddighe

Serra

et al. 2018

IJMS

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This study aims to evaluate the putative roles of a single acute dose of resveratrol (RVT) in preventing cerebral oxidative stress induced by bilateral common carotid artery occlusion, followed by reperfusion (BCCAO/R) and to investigate RVT’s ability to preserve the neuronal structural integrity. Frontal and temporal-occipital cortices were examined in two groups of adult Wistar rats, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half the rats were gavage-fed with a single dose of RVT (40 mg/per rat in 300 µL of sunflower oil as the vehicle), while the second half received the vehicle alone. In the frontal cortex, RVT pre-treatment prevented the BCCAO/R-induced increase of lipoperoxides, augmented concentrations of palmitoylethanolamide and docosahexaenoic acid, increased relative levels of the cannabinoid receptors type 1 (CB1) and 2 (CB2), and peroxisome-proliferator-activated-receptor (PPAR)-α proteins. Increased expression of CB1/CB2 receptors mirrored that of synaptophysin and post-synaptic density-95 protein. No BCCAO/R-induced changes occurred in the temporal-occipital cortex. Collectively, our results demonstrate that, in the frontal cortex, RVT pre-treatment prevents the BCCAO/R-induced oxidative stress and modulates the endocannabinoid and PPAR-α systems. The increased expression of synaptic structural proteins further suggests the possible efficacy of RVT as a dietary supplement to preserve the nervous tissue metabolism and control the physiological response to the hypoperfusion/reperfusion challenge.

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“…The neuroprotective and macrophage/microglia modulatory effects of docosahexaenoic acid (DHA), and other closely related omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA), have been well documented in compression and hemisection SCI (22)(23)(24)(25)(26)(27). Although the exact pharmacological targets of omega-3 PUFAs driving their neuroprotective effects in SCI remain elusive, a range of beneficial effects have been reported after their acute administration post-injury in models of compression and hemisection injury, including decreased axonal and myelin damage, increased neuronal and oligodendrocyte survival, reduced lipid peroxidation and COX-2 activation, and improved locomotor recovery (22,24,25,(27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic acid reduces microglia phagocytic activity via miR-124 and induces neuroprotection in rodent models of spinal cord contusion injury

Yip

Bowes

Hall

et al. 2019

Human Molecular Genetics

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Microglia are activated after spinal cord injury (SCI), but their phagocytic mechanisms and link to neuroprotection remain incompletely characterized. Docosahexaenoic acid (DHA) has been shown to have significant neuroprotective effects after hemisection and compression SCI and can directly affect microglia in these injury models. In rodent contusion SCI, we demonstrate that DHA (500 nmol/kg) administered acutely post-injury confers neuroprotection and enhances locomotor recovery, and also exerts a complex modulation of the microglial response to injury. In rodents, at 7 days after SCI, the level of phagocytosed myelin within Iba1-positive or P2Y12-positive cells was significantly lower after DHA treatment, and this occurred in parallel with an increase in intracellular miR-124 expression. Furthermore, intraspinal administration of a miR-124 inhibitor significantly reduced the DHA-induced decrease in myelin phagocytosis in mice at 7 days post-SCI. In rat spinal primary microglia cultures, DHA reduced the phagocytic response to myelin, which was associated with an increase in miR-124, but not miR-155. A similar response was observed in a microglia cell line (BV2) treated with DHA, and the effect was blocked by a miR-124 inhibitor. Furthermore, the phagocytic response of BV2 cells to stressed neurones was also reduced in the presence of DHA. In peripheral monocyte-derived macrophages, the expression of the M1, but not the M0 or M2 phenotype, was reduced by DHA, but the phagocytic activation was not altered. These findings show that DHA induces neuroprotection in contusion injury. Furthermore, the improved outcome is via a miR-124-dependent reduction in the phagocytic response of microglia.

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A nutrient combination designed to enhance synapse formation and function improves outcome in experimental spinal cord injury

Cited by 22 publications

References 68 publications

Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease

Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease

Preventive Effects of Resveratrol on Endocannabinoid System and Synaptic Protein Modifications in Rat Cerebral Cortex Challenged by Bilateral Common Carotid Artery Occlusion and Reperfusion

Docosahexaenoic acid reduces microglia phagocytic activity via miR-124 and induces neuroprotection in rodent models of spinal cord contusion injury

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