PMC:5118426 / 2128-9983 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/5118426","sourcedb":"PMC","sourceid":"5118426","source_url":"https://www.ncbi.nlm.nih.gov/pmc/5118426","text":"Table 1 Model system and human data implicating bile acids in neurodegenerative disorders.\nDisease/Phenotype Model Bile acid Mode of administration Dose or concentration Effects References\nSpinocerebellar ataxia type 1 (SCA1) Transgenic mouse with human ATXN1 with 82 CAG trinucleotide repeats under control of a Purkinje-cell promoter TUDCA Subcutaneous injection 500 mg/kg TUDCA crossed the blood-brain barrier but had no effect on cell survival Kaemmerer et al., 2001\nHuntington's disease (HD) 3-nitropropionic acid-treated rat neuronal RN33B cells TUDCA Media 100 μM Decreased apoptosis by preventing mitochondrial depolarization and outer membrane disruption Rodrigues et al., 2000\nGUDCA 500 μM\nUDCA 500 μM\nHD 3-nitropropionic acid-treated rats TUDCA Intraperitoneal injection 50 mg/kg Decreased apoptosis Keene et al., 2001\nReduced lesion volume\nPreserved sensorimotor and cognitive function\nHD R6/2 transgenic mouse with 150 CAG trinucleotide repeats in exon 1 of the huntingtin gene TUDCA Subcutaneous injection 500 mg/kg Reduced striatal cell apoptosis Keene et al., 2002\nDecreased levels of intracellular inclusions\nImproved locomotor and sensorimotor function\nParkinson's disease (PD) Sodium nitroprusside-treated human dopaminergic SH-SY5Y cells UDCA Media 50–200 μM Dose dependent inhibition of apoptosis via the PI3K- Chun and Low, 2012\nAkt/PKB pathways\nReduced ROS and reactive nitrogen species\nMaintained intracellular GSH levels\nPD Skin fibroblasts from PD patients UDCA Media 10–100 nM Restored mitochondrial function dependent upon glucocorticoid receptor activation and Akt phosphorylation Mortiboys et al., 2013\nPD MPTP-induced mouse model TUDCA Intraperitoneal injection 50 mg/kg Reduction in loss of dopaminergic neurons by preserving levels of phosphorylated JNK, reducing ROS levels, and activating the Akt pathway Castro-Caldas et al., 2012\nAlzheimer's disease (AD) Aβ-treated primary rat cortical neurons TUDCA Media 100 μM Decreased nuclear fragmentation and cytochrome c release through the PI3K pathway Solá et al., 2003\nAD Aβ-treated mouse BV-2 microglial cells UDCA Media 250 μM Anti-inflammatory effect by inhibiting NF-κB activation Joo et al., 2004\nAD Aβ-treated primary rat cortical neurons UDCA TUDCA Media 100 μM Decreased apoptosis dependent on interaction with the mineralocorticoid receptor Sola et al., 2006\nAD Double transgenic APP/PS1 mice TUDCA Diet 0.4% wt/wt Reduced amyloid plaque number Nunes et al., 2012; Ramalho et al., 2013\nDecreased injury to neurons\nImproved memory retention\nDecreased the loss of a postsynaptic marker in the hippocampus\nAmyotrophic lateral sclerosis (ALS) Mouse NSC-34 cells with the human SOD1G93A mutation GUDCA Media 50 μM Decreased cell death by blocking caspase-9 activation Vaz et al., 2015\nALS Primary mouse ventral midbrain cultures CA Media 10 μM Increased neuronal survival and promoted neurogenesis via LXR Theofilopoulos et al., 2013\nALS Clinical trial with ALS patients UDCA Oral Up to 50 mg/kg UDCA is well tolerated and well absorbed by oral administration Parry et al., 2010\nUDCA crosses the blood-brain barrier in a dose-dependent manner\nALS Clinical trial with ALS patients UDCA Oral 3.5 g/140 mL/day Slight decrease in progression of ALS but results were inconclusive Min et al., 2012\nALS Clinical trial with ALS patients TUDCA Oral 1 g, twice daily TUDCA is well tolerated Elia et al., 2016\nTreatment resulted in improved function and slowed disease progression\nPrion disease Prion infected male mice UDCA Diet 0.01% wt/wt Reduced astrogliosis Cortez et al., 2015\nProlonged survival\nCerebrotendinous xanthomatosis (CTX) Human patients CDCA Oral 15 mg/kg/day Amelioration of neurological symptoms Bjorkhem, 2013\nImproved prognosis\nRetinitis pigmentosa (RP) Homozygous P23H rhodopsin transgenic rats TUDCA Intraperitoneal injection 500 mg/kg Reduced photoreceptor loss Fernandez-Sanchez et al., 2011\nPreserved structure, function, and synaptic contacts of rods and cones\nRP Transgenic rd10 mouse model TUDCA Subcutaneous injection 500 mg/kg Higher cone cell density from decreased apoptosis Preserved structure and function of photoreceptor cells Boatright et al., 2006; Phillips et al., 2008; Oveson et al., 2011\nLight-induced retinal degeneration Light-induced retinal damage (LIRD) mouse model TUDCA Subcutaneous injection 500 mg/kg Higher cone cell density from decreased apoptosis Preserved structure and function of photoreceptor cells Boatright et al., 2006; Phillips et al., 2008; Oveson et al., 2011\nLeber congenital amaurosis Homozygous LRAT knockout mice TUDCA Subcutaneous injection 500 mg/kg Slowed cone degeneration in the ventral and central retina by preventing apoptosis and increasing ER-associated protein degradation Zhang et al., 2012; Fu and Zhang, 2014\nIn vitro retinal degeneration Whole mount cat retinas TUDCA Media 0.5 μM Greater receptive field size Xia et al., 2015\nDecreased irradiance threshold\nMaintenance of the contrast threshold\nRetinal dystrophy Primary human retinal epithelium cells TUDCA Media 100 μM Protective against H2O2-induced impairment of phagocytosis Murase et al., 2015\nRetinal detachment Subretinal injection of hyaluronic acid in rats TUDCA Intraperitoneal injection 500 mg/kg Reduced apoptosis in the outer nuclear layer of the retina Mantopoulos et al., 2011\nDecreased caspase activation and protein carbonyl production\nDiabetic retinopathy Primary rat retinal neuron cells exposed to elevated glucose TUDCA Media 100 μM Decreased apoptosis Gaspar et al., 2013\nDecreased mito-nuclear translocation of apoptosis-inducing factor (AIF)\nDecreased ROS and protein carbonyl production\nRetinal ganglion cell degeneration Intravitreal injection of NMDA in rats TUDCA Intraperitoneal injection 500 mg/kg Increased survival of retinal ganglion cells Gomez-Vicente et al., 2015\nIschemic stroke Middle cerebral artery occlusion in rats TUDCA Intravenous injection 400 mg/kg Reduction in infarct size Rodrigues et al., 2002\nReduced apoptosis\nPreserved mitochondrial integrity\nHemorrhagic stroke Collagenase TUDCA Intra-arterial injection 200 mg/kg Decreased lesion volumes, peri-hematoma apoptosis, caspase activity, NF-κB activiation; increased AKT activation, neurobehavioral improvement Rodrigues et al., 2003\nAcute neuroinflammation Intracerebro-ventricular injection with LPS in mice TUDCA Intraperitoneal injection 500 mg/kg Reduced glial cell activation Yanguas-Casás et al., 2014\nAcute neuroinflammation Primary cultures of microglial cells and astrocytes from rats treated with LPS and/or IFN-γ TUDCA Media 200 μM Reduced microglial chemotaxis and expression of MCP-1 and VCAM-1 Yanguas-Casás et al., 2014\nSleep-wake pattern Wild type and histamine deficient mice UDCA Diet 32 mg/kg Promotes wakefulness through disinhibition of the histaminergic system via GABAA receptors Yanovsky et al., 2012\nHypothalamic network activity Primary cultures of mouse posterior hypothalamus CA Media Up to 8 mM Reduced firing, synchronized network activity, and blocked GABAA and NMDA receptor activity Schubring et al., 2012\nGCA\nTCA\nDCA\nTDCA\nCDCA\nGCDCA\nTCDCA\nDHCA\nNeurotransmitter release Sympathetic ganglion neurons isolated from of adult bull frogs CA Media 1 μM Inhibits N-type calcium channel currents Lee et al., 2012\nHyperbilirubinemia Unconjugated bilirubin-treated organotypic-cultured hippocampal slices from rats GUDCA Media 50 mM Decreased cell death, NOS, glutamate release Silva et al., 2012\nGlutamate-induced neurotoxicity Glutamate-treated primary rat cortical neurons TUDCA Media 100 μM Decreased apoptosis by activating a PI3K-dependent Bad signaling pathway Castro et al., 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