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Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease
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作者 Olivier Kerdiles Méryl-Farelle Oye Mintsa Mi-mba +8 位作者 Katherine Coulombe Cyntia Tremblay VincentÉmond Martine Saint-Pierre Clémence Rouxel Line Berthiaume Pierre Julien Francesca Cicchetti Frédéric Calon 《Neural Regeneration Research》 SCIE CAS 2025年第2期574-586,共13页
There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 poly... There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease. 展开更多
关键词 6-HYDROXYDOPAMINE DOPAMINE dopamine transporter EXERCISE neurorestoration Parkinson’s disease polyunsaturated fatty acids omega-3
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AB027.Nogo-A neutralisation improves vision recovery after retinal injury
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作者 Julius Baya Mdzomba Sandrine Joly +2 位作者 Léa Rodriguez Frédéric Bretzner Vincent Pernet 《Annals of Eye Science》 2018年第1期433-433,共1页
Background:In glaucoma and after an ischemic injury of the retina,excessive activation of N-Methyl-D-Aspartate receptors,a type of glutamatergic receptors,induces the death of retinal ganglion cells and an irreversibl... Background:In glaucoma and after an ischemic injury of the retina,excessive activation of N-Methyl-D-Aspartate receptors,a type of glutamatergic receptors,induces the death of retinal ganglion cells and an irreversible vision loss.The painless loss of retinal cells does not allow for a swift diagnostic and treatment of retinal damages.There is no efficient therapy to improve retinal functions in this case.In order to develop new therapeutic approaches for retinal injury,we propose,in this study,to stimulate neuronal plasticity of the visual system by neutralising the glial protein,Nogo-A.The inhibitory action of this protein on axonal regeneration is well known in spinal cord injuries but not in the visual system.We thus studied the function of Nogo-A in vision recovery in mice.Methods:Nogo-A activities were chronically blocked by deleting its gene in KO mice and acutely,by intravitreal injections of an antibody known as 11C7.Inner retina lesions were done by injection of 0.5 or 5 nmol of NMDA in the vitreous humor.A PBS buffer was administered in control animals.The visual system functions were accessed with an optokinetic test in awake mice,by electroretinography(ERG)in the eye and visual evoked potentials in the visual cortex.Cell survival of retinal ganglion cells,amacrine and bipolar cells was evaluated on histological sections by immunofluorescence.Changes in expression of Nogo-A,its receptors and neuronal plasticity associated molecules were observed by Western blot and q-PCR.Results:At NMDA doses of≤0.5 nmol,Nogo-A KO mice show a recovery of optokinetic responses much faster than in WT mice.Surprisingly,a single injection of the antibody,11C7 was sufficient to improve VEPs of NMDA injured animals as compared to control antibody.Furthermore,ERGs showed that a dose of 0.5 nmol induced retinal lesions limited to the ganglion cell layer,with significant changes to the VEPs but without influencing photoreceptors and inner nuclear layer cells functions.However,5 nmol of NMDA affected the survival of inner nuclear layer cells and reduced by~50%their activity.Conclusions:Our results show that the neutralisation of Nogo-A can improve visual functions after injury to the inner retina.Inhibition of Nogo-A could thus be an efficient way to treat pathologies like glaucoma. 展开更多
关键词 Optokinetics visual evoked potentials NOGO-A 11C7
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小胶质细胞控制成年小鼠海马中的谷氨酸能突触
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作者 Bernadette Basilico Laura Ferrucci +26 位作者 Patrizia Ratano Maria T Golia Alfonso Grimaldi Maria Rosito Valentina Ferretti Ingrid Reverte Caterina Sanchini Maria C Marrone Maria Giubettini Valeria De Turris Debora Salerno Stefano Garofalo Marie-Kim St-Pierre Micael Carrier Massimiliano Renzi Francesca Pagani Brijesh Modi Marcello Raspa Ferdinando Scavizzi Cornelius T Gross Silvia Marinelli Marie-Ève Tremblay Daniele Caprioli Laura Maggi Cristina Limatola Silvia Di Angelantonio Davide Ragozzino 《神经损伤与功能重建》 2021年第10期F0003-F0003,共1页
小胶质细胞是调节大脑突触发育和可塑性的重要细胞类型,但其影响突触的正常功能的机制尚不清楚。在本研究中,我们通过PLX5622造成小胶质细胞耗竭,并观察其对成年野生型小鼠海马CA3-CA1突触的影响。在小胶质细胞耗竭后,与树突棘密度降低... 小胶质细胞是调节大脑突触发育和可塑性的重要细胞类型,但其影响突触的正常功能的机制尚不清楚。在本研究中,我们通过PLX5622造成小胶质细胞耗竭,并观察其对成年野生型小鼠海马CA3-CA1突触的影响。在小胶质细胞耗竭后,与树突棘密度降低相关的自发和诱发谷氨酸能活动的减少,出现未成熟突触特征以及突触的可塑性提高。小胶质细胞耗竭的小鼠在新物体识别任务的获取方面表现出缺陷。海马星形胶质细胞出现增生,但并没有神经炎症反应。在Cx3cr1-/-小鼠中,PLX不能导致海马出现上述改变。这说明CX3CL1/CX3CR1轴在小胶质细胞对突触功能的控制中有重要作用。PLX5622停用后,小胶质细胞的重新增殖,海马突触恢复,小鼠的学习功能也出现恢复。综上所述,小胶质细胞对维持成人大脑的突触的正常功能用重要的作用,去除小胶质细胞会导致谷氨酸能突触组织和活动的可逆变化。 展开更多
关键词 谷氨酸能传递 海马体 学习 小胶质细胞 神经元-小胶质细胞相互作用 突触
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A Neuronal Activity-Boosting Microglial Function in Post-Anesthetic Emergence:How Microglial-Neuronal Crosstalk May Alter States of Consciousness
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作者 Jared VanderZwaag Marie-Eve Tremblay 《Neuroscience Bulletin》 SCIE CAS 2024年第10期1590-1592,共3页
Glial cells have often been referred to as the support cells of the brain.While they do have numerous supportive functions,there is emerging research showing they play an active role in shaping the brain and behaviour... Glial cells have often been referred to as the support cells of the brain.While they do have numerous supportive functions,there is emerging research showing they play an active role in shaping the brain and behaviour.Studying the cellular and molecular crosstalk between brain cell types is immensely valuable as this research topic continues to demonstrate that many brain functions are a result of a system of cells working together,rather than any cell type independently. 展开更多
关键词 showing Boosting immense
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