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Jeremy D Hill, Viviana Zuluaga-Ramirez, Sachin Gajghate, Malika Winfield, Yuri Persidsky
BACKGROUND AND PURPOSE: The cannabinoid system exerts functional regulation of neural stem cell (NSC) proliferation and adult neurogenesis, yet not all effects of cannabinoid-like compounds seen can be attributed to the cannabinoid 1 receptor (CB1 R) or cannabinoid 2 receptor (CB2 R). The recently de-orphaned GPR55 has been shown to be activated by numerous cannabinoid ligands suggesting that GPR55 is a third cannabinoid receptor. Here we examined the role of GPR55 activation in NSC proliferation and early adult neurogenesis...
June 11, 2018: British Journal of Pharmacology
Furong Liu, Meiling Wu, Jiejing Kai, Jingyin Dong, Binbin Zhang, Luna Liu, Feng Zhu, Ling-Hui Zeng
Previous studies have demonstrated that rapamycin prevents seizure-induced anxiety-like behaviors. However, rapamycin had been used at a higher dose of 3mg/kg and resulted in side effects in immature animals. The present work was designed to explore whether a lower dose of rapamycin has similar efficacy but has milder side effects. Acute seizures were induced by injection of pilocarpine at postnatal 10 day Sprague-Dawley rats. Western blot analysis was used to detect changes in mTOR pathway after seizure...
June 8, 2018: International Journal of Neuroscience
Dongdong Chen, Ling Wei, Zhi-Ren Liu, Jenny J Yang, Xiaohuan Gu, Zheng Z Wei, Li-Ping Z Liu, Shan Ping Yu
Ischemic stroke remains a serious threat to human life. Generation of neuronal and vascular cells is an endogenous regenerative mechanism in the adult brain, which may contribute to tissue repair after stroke. However, the regenerative activity is typically insufficient for significant therapeutic effects after brain injuries. Pyruvate kinase isoform M2 (PKM2) is a key regulator for energy metabolism. PKM2 also has nonmetabolic roles involving regulations of gene expression, cell proliferation, and migration in cancer cells as well as noncancerous cells...
June 4, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Anna Gorelik, Tamar Sapir, Lihi Ben-Reuven, Orly Reiner
The complement system, which is part of the innate immune response system, has been recently shown to participate in multiple key processes in the developing brain. Here we aimed to elucidate downstream signaling responses linking complement C3, a key molecule of the pathway, to small GTPases, known to affect the cytoskeleton. The expression pattern of the activated small GTPase Rac1 resembled that of complement C3. C3-deficient mice exhibited reduced Rac1 and elevated RhoA activity in comparison with control mice...
2018: Frontiers in Molecular Neuroscience
Ludmila Belayev, Sung-Ha Hong, Hemant Menghani, Shawn J Marcell, Andre Obenaus, Raul S Freitas, Larissa Khoutorova, Veronica Balaszczuk, Bokkyoo Jun, Reinaldo B Oriá, Nicolas G Bazan
Docosahexaenoic acid (DHA) and neuroprotectin D1 (NPD1) are neuroprotective after experimental ischemic stroke. To explore underlying mechanisms, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo) and treated with DHA (5 mg/kg, IV) or NPD1 (5 μg/per rat, ICV) and vehicles 1 h after. Neuro-behavioral assessments was conducted on days 1, 2, and 3, and on week 1, 2, 3, or 4. BrdU was injected on days 4, 5, and 6, immunohistochemistry was performed on week 2 or 4, MRI on day 7, and lipidomic analysis at 4 and 5 h after onset of stroke...
June 1, 2018: Molecular Neurobiology
JiHoon Kang, Wanyeon Kim, HyunJeong Seo, EunGi Kim, Beomseok Son, Sungmin Lee, Gaeul Park, Sunmi Jo, Changjong Moon, HyeSook Youn, BuHyun Youn
Cranial irradiation is the main therapeutic strategy for treating primary and metastatic brain tumors. However, radiation is well-known to induce several unexpected side effects including emotional disorders. Although radiation-induced depression may cause decreased quality of life after radiotherapy, investigations of its molecular mechanism and therapeutic strategies are still insufficient. In this study, we found that behavioral symptoms of depression on mice models with the decrease of BrdU/NeuN- and Dcx-positive populations and MAP-2 expression in hippocampus were induced by cranial irradiation, and transthyretin (TTR) was highly expressed in hippocampus after irradiation...
May 30, 2018: Scientific Reports
James D O'Leary, Alan E Hoban, John F Cryan, Olivia F O'Leary, Yvonne M Nolan
Adolescence is a critical period for postnatal brain maturation and a time during which there is increased susceptibility to developing emotional and cognitive-related disorders. Exercise during adulthood has been shown to increase hippocampal plasticity and enhance cognition. However, the impact of exercise initiated in adolescence, on brain and behaviour in adulthood is not yet fully explored or understood. The aim of this study was to compare the impact of voluntary exercise that was initiated either during adolescence or early adulthood on cognitive performance in hippocampal and amygdala-dependent fear conditioning tasks in adulthood...
May 14, 2018: Neuropharmacology
Miao Hongsheng, Runming Li, Cong Han, Xiuzhen Lu, Hang Zhang
Intracerebral hemorrhage (ICH) is a devastating disease worldwide with increasing mortality. The present study investigated whether minocycline was neuroprotective and induced M2 microglial polarization via up-regulation of the TrkB/BDNF pathway after ICH. ICH was induced via injection of autologous blood into 150 Sprague-Dawley (S-D) rats. A selective TrkB antagonist (ANA 12) and agonist (HIOC) were used to investigate the mechanism of minocycline-induced neuroprotection. Minocycline improved ICH-induced neurological deficits and reduced M1 microglia marker protein (CD68, CD16) expression as well as M2 microglial polarization (CD206 and arginase 1 protein)...
May 23, 2018: Journal of Neurophysiology
Fanny Sandrine Martineau, Surajit Sahu, Vanessa Plantier, Emmanuelle Buhler, Fabienne Schaller, Lauriane Fournier, Geneviève Chazal, Hiroshi Kawasaki, Alfonso Represa, Françoise Watrin, Jean-Bernard Manent
The neocortex is a 6-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neurons by knocking down doublecortin (Dcx), a crucial effector of migration, and show that misplaced neurons fail to properly form dendrites, spines, and functional glutamatergic and GABAergic synapses...
May 18, 2018: Cerebral Cortex
Xiao Yang, Ke-Yi Geng, Yan-Shuang Zhang, Jin-Fan Zhang, Ke Yang, Jia-Xiang Shao, Wei-Liang Xia
AIMS: Sirt3 is one member of the NAD+ -dependent protein deacetylase family and plays crucial roles in diverse aspects of mammalian biological function. Then the role of Sirt3 on ischemia stroke is unknown. METHODS: To examine the effect of Sirt3 on ischemic stroke, we performed transient middle cerebral artery occlusion (tMCAO) in adult male Sirt3 knockout (KO) and wild-type (WT) mice. RESULTS: The level of Sirt3 in infarct region is decreased after ischemic stroke...
May 18, 2018: CNS Neuroscience & Therapeutics
Dailiany Orechio, Bruna Andrade Aguiar, Giovanne Baroni Diniz, Jackson Cioni Bittencourt, Carlos A Haemmerle, Ii-Sei Watanabe, Maria Angelica Miglino, Patricia Castelucci
The existence of neurogenesis in the adult brain is a widely recognized phenomenon, occurring in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyrus in several vertebrate species. Neural precursors originated in the SVZ migrate to the main olfactory bulb (MOB), originating the rostral migratory stream (RMS) in the process. To better understand the formation of the adult neurogenic niches in dogs, we investigated the cellular composition and morphological organization of these areas in 57 days-old dog fetuses...
May 12, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Govindarajan Karthivashan, Shin-Young Park, Mee-Hyang Kweon, Joonsoo Kim, Md Ezazul Haque, Duk-Yeon Cho, In-Su Kim, Eun-Ah Cho, Palanivel Ganesan, Dong-Kug Choi
The Salicornia europaea L. (SE) plant is a halophyte that has been widely consumed as a seasoned vegetable, and it has been recently reported to counteract chronic diseases related to oxidative and inflammatory stress. In this study, we performed an initial phytochemical analysis with in vitro biochemical tests and chromatographic profiling of desalted and enzyme-digested SE ethanol extract (SE-EE). Subsequently, we evaluated the anti-neuroinflammatory and ameliorative potential of SE-EE in LPS-inflicted BV-2 microglial cells and scopolamine-induced amnesic C57/BL6N mice, respectively...
May 8, 2018: Scientific Reports
Sara Cipriani, Isidre Ferrer, Eleonora Aronica, Gabor G Kovacs, Catherine Verney, Jeannette Nardelli, Suonavy Khung, Anne-Lise Delezoide, Ivan Milenkovic, Sowmyalakshmi Rasika, Philippe Manivet, Jean-Louis Benifla, Nicolas Deriot, Pierre Gressens, Homa Adle-Biassette
Neuropathological conditions might affect adult granulogenesis in the adult human dentate gyrus. However, radial glial cells (RGCs) have not been well characterized during human development and aging. We have previously described progenitor and neuronal layer establishment in the hippocampal pyramidal layer and dentate gyrus from embryonic life until mid-gestation. Here, we describe RGC subtypes in the hippocampus from 13 gestational weeks (GW) to mid-gestation and characterize their evolution and the dynamics of neurogenesis from mid-gestation to adulthood in normal and Alzheimer's disease (AD) subjects...
May 2, 2018: Cerebral Cortex
Peter Rotheneichner, Maria Belles, Bruno Benedetti, Richard König, Dominik Dannehl, Christina Kreutzer, Pia Zaunmair, Maren Engelhardt, Ludwig Aigner, Juan Nacher, Sebastien Couillard-Despres
Neurogenesis in the healthy adult murine brain is based on proliferation and integration of stem/progenitor cells and is thought to be restricted to 2 neurogenic niches: the subventricular zone and the dentate gyrus. Intriguingly, cells expressing the immature neuronal marker doublecortin (DCX) and the polysialylated-neural cell adhesion molecule reside in layer II of the piriform cortex. Apparently, these cells progressively disappear along the course of ageing, while their fate and function remain unclear...
July 1, 2018: Cerebral Cortex
Priya Ghumatkar, Vaibhavi Peshattiwar, Sachin Patil, Suraj Muke, David Whitfield, David Howlett, Paul Francis, Sadhana Sathaye
OBJECTIVES: Considering the deleterious effect of Aβ1-42, a study was designed to evaluate the effect of phloretin on altered synaptic proteins and adult hippocampal neurogenesis in Aβ1-42-injected Wistar rats. METHODS: The rats were pretreated with 5 mg/kg p.o dose of phloretin and donepezil (positive control) for 28 days, followed by intrahippocampal injections of aggregated Aβ1-42. After termination, perfused brains were isolated and subjected to Western blot and immunohistochemistry (IHC) analysis...
April 23, 2018: Journal of Pharmacy and Pharmacology
Nataliya Di Donato, Andrew E Timms, Kimberly A Aldinger, Ghayda M Mirzaa, James T Bennett, Sarah Collins, Carissa Olds, Davide Mei, Sara Chiari, Gemma Carvill, Candace T Myers, Jean-Baptiste Rivière, Maha S Zaki, Joseph G Gleeson, Andreas Rump, Valerio Conti, Elena Parrini, M Elizabeth Ross, David H Ledbetter, Renzo Guerrini, William B Dobyns
PurposeTo estimate diagnostic yield and genotype-phenotype correlations in a cohort of 811 patients with lissencephaly or subcortical band heterotopia.MethodsWe collected DNA from 756 children with lissencephaly over 30 years. Many were tested for deletion 17p13.3 and mutations of LIS1, DCX, and ARX, but few other genes. Among those tested, 216 remained unsolved and were tested by a targeted panel of 17 genes (ACTB, ACTG1, ARX, CRADD, DCX, LIS1, TUBA1A, TUBA8, TUBB2B, TUBB, TUBB3, TUBG1, KIF2A, KIF5C, DYNC1H1, RELN, and VLDLR) or by whole-exome sequencing...
April 19, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Andrea Aguilar-Arredondo, Angélica Zepeda
The dentate gyrus (DG) is a neurogenic structure that exhibits functional and structural reorganization after injury. Neurogenesis and functional recovery occur after brain damage, and the possible relation between both processes is a matter of study. We explored whether neurogenesis and the activation of new neurons correlated with DG recovery over time. We induced a DG lesion in young adult rats through the intrahippocampal injection of kainic acid and analyzed functional recovery and the activation of new neurons after animals performed a contextual fear memory task (CFM) or a control spatial exploratory task...
April 16, 2018: Brain Structure & Function
A Ra Kho, Ok Joon Kim, Jeong Hyun Jeong, Ji Min Yu, Hye Sun Kim, Bo Young Choi, Sang Won Suh, Tae Nyoung Chung
BACKGROUND: Global cerebral ischemia (GCI) is a major obstacle for cardiac arrest survival. Recent studies have suggested the possibility of mesenchymal stem cell (MSC) as a novel therapeutic option for GCI, but these results were limited to the neuroprotective effects of MSCs. Therefore, we aimed to investigate specific characteristics of neurogenesis after transient GCI, and to assess the effect of MSC on these characteristics. METHODS: Adult male Sprague-Dawley rats were subjected to 7 min of transient GCI and randomized into 7 groups: baseline, MSC, and control administered groups, to be analyzed at 2, 3, and 4 weeks after GCI, respectively...
June 15, 2018: Brain Research
Bianca Gazieri Castelucci, Sílvio Roberto Consonni, Viviane Souza Rosa, Lucimara Aparecida Sensiate, Paula Cristina Rugno Delatti, Lúcia Elvira Alvares, Paulo Pinto Joazeiro
Animal models commonly serve as a bridge between in vitro experiments and clinical applications; however, few physiological processes in adult animals are sufficient to serve as proof-of-concept models for cartilage regeneration. Intriguingly, some rodents, such as young adult mice, undergo physiological connective tissue modifications to birth canal elements such as the pubic symphysis during pregnancy; therefore, we investigated whether the differential expression of cartilage differentiation markers is associated with cartilaginous tissue morphological modifications during these changes...
2018: PloS One
Ming-Liang Zhao, Shi-Jin Chen, Xiao-Hong Li, Li-Na Wang, Feng Chen, Shi-Jiang Zhong, Cheng Yang, Sheng-Kai Sun, Jian-Jun Li, Hua-Jiang Dong, Yue-Qing Dong, Yi Wang, Chong Chen
Electrical excitability by membrane depolarization is crucial for survival and maturation of newborn cells in the dentate gyrus of the hippocampus. However, traditional technology for membrane depolarization lacks temporal and spatial precision. Optogenetics can be used to activate channelrhodopsin-2 (ChR2), allowing cationic current to depolarize genetically targeted cells. In this study, we used ChR2-EGFP driven by doublecortin (DCX) to promote survival and maturation of newborn cells in the dentate gyrus after traumatic brain injury (TBI)...
2018: Journal of Alzheimer's Disease: JAD
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