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organotypic culture

Cara L Croft, Wendy Noble
Alzheimer's disease, the most common cause of dementia, is a progressive neurodegenerative disorder characterised by amyloid-beta deposits in extracellular plaques, intracellular neurofibrillary tangles of aggregated tau, synaptic dysfunction and neuronal death. There are no cures for AD and current medications only alleviate some disease symptoms. Transgenic rodent models to study Alzheimer's mimic features of human disease such as age-dependent accumulation of abnormal beta-amyloid and tau, synaptic dysfunction, cognitive deficits and neurodegeneration...
2018: F1000Research
ArunSundar MohanaSundaram, Thukani Sathanantham Shanmugarajan, Velayutham Ravichandiran
Cognitive impulsivity, a form of suboptimal cost-benefit decision making is an illustrious attribute of an array of neurodegenerative diseases including Alzheimer's Disease (AD). In this study, delay discounting paradigm was used to assess the effect of 3,4-dihydroxyphenylethanol (DOPET) on cognitive impulsivity-in an oA42i (oligomeric amyloid β1-42 plus ibotenic acid) induced AD mouse model-using a non-spatial T-maze task. The results depicted that oA42i administration elevated cognitive impulsivity, whereas DOPET treatment attenuated the impulsive behavior and matched the choice of the sham-operated controls...
June 14, 2018: ACS Chemical Neuroscience
Alissa Piekarski, Gurueswar Nagarajan, Peter Ishola, Joshua Flees, Elizabeth S Greene, Wayne J Kuenzel, Takeshi Ohkubo, Helena Maier, Walter G Bottje, Mark A Cline, Sami Dridi
Autophagy, a highly conserved intracellular self-digestion process, plays an integral role in maintaining cellular homeostasis. Although emerging evidence indicate that the endocrine system regulates autophagy in mammals, there is still a scarcity of information on autophagy in avian (non-mammalian) species. Here, we show that intracerebroventricular administration of leptin reduces feed intake, modulates the expression of feeding-related hypothalamic neuropeptides, activates leptin receptor and signal transducer and activator of transcription (Ob-Rb/STAT) pathway, and significantly increases the expression of autophagy-related proteins (Atg3, Atg5, Atg7, beclin1, and LC3B) in chicken hypothalamus, liver, and muscle...
2018: Frontiers in Physiology
Hyejin Jin, In-Hye Ham, Hye Jeong Oh, Cheong A Bae, Da Keun Lee, Young-Bae Kim, Sang-Yong Son, Yong-Joon Chwae, Sang-Uk Han, Rolf A Brekken, Hoon Hur
Discoidin domain receptor 1 (DDR1) is activated by fibrillar (triple-helical) collagens and collagen IV, which are major components of tumor stroma; thus, DDR1 might be critical mediator of communication between cancer cells and stroma. The aim of this study was to investigate the effect of DDR1 inhibition on stroma-induced peritoneal metastasis in gastric carcinoma (GC). We analyzed by immunohistochemistry the correlation between DDR1 expression and the pattern of recurrence in GC tissues from a previously characterized and established GC patient cohort...
June 4, 2018: Molecular Cancer Research: MCR
Joel Wellbourne-Wood, Jean-Yves Chatton
To investigate the enormous complexity of the functional and pathological brain there are a number of possible experimental model systems to choose from. Depending on the research question choosing the appropriate model may not be a trivial task, and given the dynamic and intricate nature of an intact living brain several models might be needed to properly address certain questions. In this review we aim to provide an overview of neural cell and tissue culture, reflecting on historic methodological milestones and providing a brief overview of the state-of-the-art...
May 30, 2018: ACS Chemical Neuroscience
Wadim Vodovozov, Justus Schneider, Shehabeldin Elzoheiry, Jan-Oliver Hollnagel, Andrea Lewen, Oliver Kann
Gamma oscillations (30-100 Hz) represent a physiological fast brain rhythm that occurs in many cortex areas in awake mammals, including humans. They associate with sensory perception, voluntary movement, and memory formation and require precise synaptic transmission between excitatory glutamatergic neurons and inhibitory GABAergic interneurons such as parvalbumin-positive basket cells. Notably, gamma oscillations are exquisitely sensitive to shortage in glucose and oxygen supply (metabolic stress), with devastating consequences for higher cognitive functions...
May 28, 2018: Pflügers Archiv: European Journal of Physiology
Mattias Svensson, Puran Chen
Biomedical research aiming to understand the molecular basis of human lung tissue development, homeostasis and disease, or to develop new therapies for human respiratory diseases, requires models that faithfully recapitulate the human condition. This has stimulated biologists and engineers to develop in vitro organotypic models mimicking human respiratory tissues. In this chapter, we provide examples of different types of model systems ranging from simple unicellular cultures to more complex multicellular systems...
May 29, 2018: Current Topics in Microbiology and Immunology
Daniel W M Acker, Irene Wong, Mihwa Kang, Suzanne Paradis
OBJECTIVE: We previously discovered a role for the extracellular domain of the transmembrane protein semaphorin 4D (Sema4D) as a fast-acting, selective, and positive regulator of functional γ-aminobutyric acid (GABA)ergic synapse formation in hippocampal neuronal culture. We also demonstrated that Sema4D treatment increases inhibitory tone and suppresses hyperexcitability in an organotypic hippocampal slice culture model of epilepsy. Here, we investigate the ability of Sema4D to promote GABAergic synapse formation and suppress seizure activity in vivo in adult mice...
May 25, 2018: Epilepsia
Brahim Gargouri, Nizar M Yousif, Michèle Bouchard, Hamadi Fetoui, Bernd L Fiebich
BACKGROUND: Pyrethroids, such as bifenthrin (BF), are among the most widely used class of insecticides that pose serious risks to human and wildlife health. Pyrethroids are proposed to affect astrocytic functions and to cause neuron injury in the central nervous system (CNS). Microglia are key cells involved in innate immune responses in the CNS, and microglia activation has been linked to inflammation and neurotoxicity. However, little information is known about the effects of BF-induced toxicity in primary microglial cells as well as in organotypic hippocampal slice cultures (OHSCs)...
May 24, 2018: Journal of Neuroinflammation
Kentaro Ishida, Tetsuichiro Saito, Toshiyuki Mitsui
A Merkel cell-neurite complex is a touch receptor composed of specialized epithelial cells named Merkel cells and peripheral sensory nerves in the skin. Merkel cells are found in touch-sensitive skin components including whisker follicles. The nerve fibers that innervate Merkel cells of a whisker follicle extend from the maxillary branch of the trigeminal ganglion. Whiskers as a sensory organ attribute to the complicated architecture of the Merkel cell-neurite complex, and therefore it is intriguing how the structure is formed...
May 22, 2018: Development, Growth & Differentiation
J M Kim, S Choi, S W Lee, K Park
Branching morphogenesis is a crucial part of early developmental processes in diverse organs, but the detailed mechanism of this morphogenic event remains to be elucidated. Here we introduce an unknown mechanism leading to branching morphogenesis using mouse embryonic organotypic cultures with time-lapse live imaging. We found spatially expressed L-type voltage-dependent Ca2+ channels (VDCCs) in the peripheral layers of developing epithelial buds and identified the VDCCs as a core signaling mediator for patterning branching architecture...
May 15, 2018: Scientific Reports
Bhavana Muralidharan, Leora D'Souza, Shubha Tole
We established an efficient cell culture assay that permits combinatorial genetic perturbations in hippocampal progenitors to examine cell-autonomous mechanisms of fate specification. The procedure begins with ex vivo electroporation of isolated, intact embryonic brains, in a manner similar to in utero electroporation but with greatly improved access and targeting. The electroporated region is then dissected and transiently maintained in organotypic explant culture, followed by dissociation and plating of cells on coverslips for in vitro culture...
2018: Journal of Experimental Neuroscience
Stefanie Inglis, Karl Heinrich Schneider, Janos M Kanczler, Heinz Redl, Richard O C Oreffo
Decellularized matrices offer a beneficial substitute for biomimetic scaffolds in tissue engineering. The current study examines the potential of decellularized placental vessel sleeves (PVS) as a periosteal protective sleeve to enhance bone regeneration in embryonic day 18 chick femurs contained within the PVS and cultured organotypically over a 10 day period. The femurs are inserted into decellularized biocompatibility-tested PVS and maintained in an organotypic culture for a period of 10 days. In femurs containing decellularized PVS, a significant increase in bone volume (p < 0...
May 14, 2018: Advanced Healthcare Materials
Rebecca M Lewis, Jesse J Keller, Liangcai Wan, Jennifer S Stone
Permanent hearing loss is often a result of damage to cochlear hair cells, which mammals are unable to regenerate. Non-mammalian vertebrates such as birds replace damaged hair cells and restore hearing function, but mechanisms controlling regeneration are not understood. The secreted protein bone morphogenetic protein 4 (BMP4) regulates inner ear morphogenesis and hair cell development. To investigate mechanisms controlling hair cell regeneration in birds, we examined expression and function of BMP4 in the auditory epithelia (basilar papillae) of chickens of either sex after hair cell destruction by ototoxic antibiotics...
May 2, 2018: Hearing Research
Benedetta Rosato, Danilo Ranieri, Monica Nanni, Maria Rosaria Torrisi, Francesca Belleudi
The tumor suppressor epithelial isoform of the fibroblast growth factor receptor 2 (FGFR2b) induces human keratinocyte early differentiation. Moreover, protein kinases C (PKCs) are known to regulate the differentiation program in several cellular contexts, including keratinocytes. Therefore, in this paper we propose to clarify if FGFR2b could play a role also in the late steps of keratinocyte differentiation and to assess if this receptor-induced process would sequentially involve PKCδ and PKCα isoforms. Immunofluorescence, biochemical, and molecular approaches, performed on 2D cultures or 3D organotypic rafts of human keratinocytes overexpressing FGFR2b by stable transduction, showed that receptor signaling induced the precocious onset and an accelerated progression of keratinocyte differentiation, indicating that FGFR2b is a crucial regulator of the entire program of keratinocyte differentiation...
May 11, 2018: Cell Death & Disease
Sophia M Orbach, Marion F Ehrich, Padmavathy Rajagopalan
High-throughput screening (HTS) of liver toxicants can bridge the gap in understanding adverse effects of chemicals on humans. Toxicity testing of mixtures is time consuming and expensive, since the number of possible combinations increases exponentially with the number of chemicals. The combination of organotypic culture models and HTS assays can lead to the rapidly evaluation of chemical toxicity in a cost and time-effective manner while prioritizing chemicals that warrant additional investigation. We describe the design, assembly and toxicant response of multi-cellular hepatic organotypic culture models comprised of primary human or rat cells assembled in 96-well plates (denoted as μOCMs)...
May 8, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Chang Guo, Alison Buckley, Tim Marczylo, Joanna Seiffert, Isabella Römer, James Warren, Alan Hodgson, Kian Fan Chung, Timothy W Gant, Rachel Smith, Martin O Leonard
Experimental modeling to identify specific inhalation hazards for nanomaterials has in the main focused on in vivo approaches. However, these models suffer from uncertainties surrounding species-specific differences and cellular targets for biologic response. In terms of pulmonary exposure, approaches which combine 'inhalation-like' nanoparticulate aerosol deposition with relevant human cell and tissue air-liquid interface cultures are considered an important complement to in vivo work. In this study, we utilized such a model system to build on previous results from in vivo exposures, which highlighted the small airway epithelium as a target for silver nanoparticle (AgNP) deposition...
May 11, 2018: Nanotoxicology
Yan Li, Pengcheng Wang, Chuanlin Hu, Kun Wang, Qing Chang, Lieju Liu, Zhenggang Han, Yang Shao, Ying Zhai, Zhengyu Zuo, Michael Mak, Zhiyong Gong, Yang Wu
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
May 10, 2018: Scientific Reports
David Romeo-Guitart, Tatiana Leiva-Rodríguez, María Espinosa-Alcantud, Núria Sima, Alejandro Vaquero, Helena Domínguez-Martín, Diego Ruano, Caty Casas
Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to exert effects opposite those of SIRT1; however, its roles in neurodegeneration and neuron response after nerve injury remain unclear. Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy...
May 10, 2018: Cell Death & Disease
Leila Azizzadeh Pormehr, Narsis Daftarian, Shahin Ahmadian, Mozhgan Rezaei Kanavi, Hamid Ahmadieh, Mahshid Shafiezadeh
The splicing factor PRPF31 is the most commonly mutated general splicing factor in the retinitis pigmentosa. We used a rapid, convenient and cost effective transfection method with an efficient PRPF31 knockdown in HORFC in order to study the effect of PRPF31 downregulation on retinal gene expressions in an ex vivo model. Modified calcium phosphate method was used to transfect HORFC by PRPF31 siRNA. Different times and doses of siRNA for transfection were assayed and optimum condition was obtained. PRPF31 mRNA and protein downregulation were assessed by qRTPCR and Western blot...
May 10, 2018: Journal of Cellular Biochemistry
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