Transplantation of NSC-derived cholinergic neuron-like cells improves cognitive function in APP/PS1 transgenic mice.

Abstract:

:The ability to selectively control the differentiation of neural stem cells (NSCs) into cholinergic neurons in vivo would be an important step toward cell replacement therapy. First, green fluorescent protein (GFP)-NSCs were induced to differentiate into cholinergic neuron-like cells (CNLs) with retinoic acid (RA) pre-induction followed by nerve growth factor (NGF) induction. Then, these CNLs were transplanted into bilateral hippocampus of APP/PS1 transgenic mice. Behavioral parameters showed by Morris water maze (MWM) tests and the percentages of GFP-labeled cholinergic neurons of CNL transplanted mice were compared with those of controls. Brain levels of choline acetyltransferase (ChAT) mRNA and proteins were analyzed by quantitative real-time PCR and Western blotting, ChAT activity and acetylcholine (ACh) concentration were also evaluated by ChAT activity and ACh concentration assay kits. Immunofluorescence analysis showed that 80.3±1.5% NSCs differentiated into CNLs after RA pre-induction followed by NGF induction in vitro. Three months after transplantation, 82.4±6.3% CNLs differentiated into cholinergic neurons in vivo. APP/PS1 mice transplanted with CNLs showed a significant improvement in learning and memory ability compared with control groups at different time points. Furthermore, CNLs transplantation dramatically increased in the expressions of ChAT mRNA and protein, as well ChAT activity and ACh concentration in APP/PS1 mice. Our findings support the prospect of using NSC-derived CNLs in developing therapies for Alzheimer's disease (AD).

journal_name

Neuroscience

journal_title

Neuroscience

authors

Gu G,Zhang W,Li M,Ni J,Wang P

doi

10.1016/j.neuroscience.2015.01.073

subject

Has Abstract

pub_date

2015-04-16 00:00:00

pages

81-92

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(15)00141-4

journal_volume

291

pub_type

杂志文章
  • Burst firing in identified rat geniculate interneurons.

    abstract::We used whole-cell patch recording to study 102 local interneurons in the rat dorsal lateral geniculate nucleus in vitro. Input impedance with this technique (607.0+/-222.4 MOhm) was far larger than that measured with sharp electrode techniques, suggesting that interneurons may be more electrotonically compact than pr...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/s0306-4522(98)00665-4

    authors: Zhu JJ,Uhlrich DJ,Lytton WW

    更新日期:1999-01-01 00:00:00

  • Free radicals accelerate the decay of long-term potentiation in field CA1 of guinea-pig hippocampus.

    abstract::Free radicals have been implicated in a number of pathological conditions. To evaluate the neurophysiological consequences of free radical exposure, slices of hippocampus isolated from guinea-pigs were exposed to hydrogen peroxide which reacts with tissue iron to generate hydroxyl free radicals. Long-term potentiation...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(91)90060-2

    authors: Pellmar TC,Hollinden GE,Sarvey JM

    更新日期:1991-01-01 00:00:00

  • Systemic capsaicin in the adult rat differentially affects gene expression for neuropeptides and neurotrophin receptors in primary sensory neurons.

    abstract::While systemic capsaicin in adult rats is known to reduce substance P and somatostatin in primary sensory nerves, it is still unknown if it also affects the production of these peptides at the genetic level. Therefore, we examined the effects of systemically administered capsaicin on the expression of the beta-preprot...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/s0306-4522(96)00334-x

    authors: Kashiba H,Ueda Y,Senba E

    更新日期:1997-01-01 00:00:00

  • Region-specific aging of the human brain as evidenced by neurochemical profiles measured noninvasively in the posterior cingulate cortex and the occipital lobe using 1H magnetic resonance spectroscopy at 7 T.

    abstract::The concentrations of fourteen neurochemicals associated with metabolism, neurotransmission, antioxidant capacity, and cellular structure were measured noninvasively from two distinct brain regions using 1H magnetic resonance spectroscopy. Seventeen young adults (age 19-22years) and sixteen cognitively normal older ad...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2017.04.035

    authors: Marjańska M,McCarten JR,Hodges J,Hemmy LS,Grant A,Deelchand DK,Terpstra M

    更新日期:2017-06-23 00:00:00

  • Housing condition-related changes involved in reversal learning and its c-Fos associated activity in the prefrontal cortex.

    abstract::Our study examined how different housing conditions modulated the acquisition of a spatial reference memory task and also, a reversal task in the 4-radial arm water maze (4-RAWM). The animals were randomly assigned to standard or enriched cages, and, as a type of complementary stimulation along with the environmental ...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2015.08.038

    authors: Sampedro-Piquero P,Zancada-Menendez C,Begega A

    更新日期:2015-10-29 00:00:00

  • Fine structure of the dorsal part of the nucleus submedius of the rat thalamus: an anatomical study with reference to possible pain pathways.

    abstract::The dorsal portion of the nucleus submedius of the rat thalamus receives spinal and trigeminal projections which may convey noxious inputs. The present study was undertaken to analyse the fine structure of the nucleus with particular reference to a possible trigemino-thalamo-prefrontal cortical pathway relaying in nuc...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(88)90133-9

    authors: Ma W,Peschanski M,Ohara PT

    更新日期:1988-07-01 00:00:00

  • Expression Levels of SMAD Specific E3 Ubiquitin Protein Ligase 2 (Smurf2) and its Interacting Partners Show Region-specific Alterations During Brain Aging.

    abstract::Aging occurs due to a combination of several factors, such as telomere attrition, cellular senescence, and stem cell exhaustion. The telomere attrition-dependent cellular senescence is regulated by increased levels of SMAD specific E3 ubiquitin protein ligase 2 (smurf2). With age smurf2 expression increases and Smurf2...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2020.04.003

    authors: Sasik MUT,Eravsar ETK,Kinali M,Ergul AA,Adams MM

    更新日期:2020-06-01 00:00:00

  • Central Nervous System-Derived Exosomal Alpha-Synuclein in Serum May Be a Biomarker in Parkinson's Disease.

    abstract::Parkinson's disease (PD) is a common movement disorder. Alpha-synuclein (α-synuclein) plays a critical role in PD. In this study, we evaluated the level of central nervous system (CNS)-derived exosomal α-synuclein in serum, which may be regarded as a specific peripheral biomarker for PD. We recruited patients with PD ...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2019.05.015

    authors: Si X,Tian J,Chen Y,Yan Y,Pu J,Zhang B

    更新日期:2019-08-10 00:00:00

  • Acquisition of a palatable-food-sustained appetitive behavior in satiated rats is dependent on the dopaminergic response to this food in limbic areas.

    abstract::Rats exposed to repeated unavoidable stress show decreased dopamine output in the nucleus accumbens shell (NAcS) and do not acquire vanilla sugar (VS)-sustained appetitive behavior (VAB). Rats treated with lithium for 3 weeks also show decreased NAcS dopamine output, yet they acquire VAB. Feeding a novel palatable foo...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/s0306-4522(03)00383-x

    authors: Gambarana C,Masi F,Leggio B,Grappi S,Nanni G,Scheggi S,De Montis MG,Tagliamonte A

    更新日期:2003-01-01 00:00:00

  • Concerted enhancement of calcium influx, neurotransmitter release and protein phosphorylation by a phorbol ester in cultured brain neurons.

    abstract::We have recently shown that the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate enhances the depolarization induced, calcium dependent release of [3H]dopamine from cultured brain neurons in the rat. In the present study the effects of 12-O-tetradecanoyl-phorbol-13-acetate on the kinetic parameters of depolarizatio...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(86)90140-5

    authors: Zurgil N,Yarom M,Zisapel N

    更新日期:1986-12-01 00:00:00

  • Properties of Ca2+ currents in acutely dissociated neurons of the chick ciliary ganglion: inhibition by somatostatin-14 and somatostatin-28.

    abstract::Whole-cell voltage-clamp recordings were made from acutely dissociated neurons obtained from the embryonic chick ciliary ganglion. Recording pipettes were filled with salines containing 120 mM CsCl or 120 mM tetraethylammonium-Cl. Application of depolarizing voltage commands evoked L-type Ca2+ currents and, at voltage...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(91)90086-4

    authors: Dryer SE,Dourado MM,Wisgirda ME

    更新日期:1991-01-01 00:00:00

  • Signaling mechanisms of down-regulation of voltage-activated Ca2+ channels by transient receptor potential vanilloid type 1 stimulation with olvanil in primary sensory neurons.

    abstract::Olvanil ((N-vanillyl)-9-oleamide), a non-pungent transient receptor potential vanilloid type 1 agonist, desensitizes nociceptors and alleviates pain. But its molecular targets and signaling mechanisms are little known. Calcium influx through voltage-activated Ca(2+) channels plays an important role in neurotransmitter...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2006.03.023

    authors: Wu ZZ,Chen SR,Pan HL

    更新日期:2006-08-11 00:00:00

  • Development of the suprachiasmatic nucleus in rats during ontogenesis: serotonin-immunopositive fibers.

    abstract::The innervation of the suprachiasmatic nucleus by serotoninergic fibers has been studied in rats from the 22nd embryonic until the 21st postnatal day. The serotoninergic fibers were detected with the pre-embedding immunocytochemical technique at the electron-microscopic level using antibodies to serotonin. Serotonin-i...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(94)90163-5

    authors: Ugrumov MV,Popov AP,Vladimirov SV,Kasmambetova S,Novodjilova AP,Tramu G

    更新日期:1994-01-01 00:00:00

  • Thyroid hormone regulates excitability in central neurons from postnatal rats.

    abstract::A lack of thyroid hormone in the postnatal period causes an irreversible mental retardation, characterized by a slowing of thoughts and movements accompanied by prolonged latencies of several evoked potentials and slowed electroencephalographic rhythms. Here we show that in cultured hippocampal and cortical neurons fr...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2004.01.047

    authors: Hoffmann G,Dietzel ID

    更新日期:2004-01-01 00:00:00

  • Amphetamine-induced increase in motor activity is correlated with higher firing rates of non-dopamine neurons in substantia nigra and ventral tegmental area.

    abstract::The responses of non-dopamine neurons in substantia nigra and ventral tegmental area to systemic amphetamine were investigated in the behaving rat chronically implanted with multiple fine-wire electrodes. The neurons were identified with electrophysiological criteria requiring that the signals be of biphasic shape, sh...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(88)90343-0

    authors: Olds ME

    更新日期:1988-02-01 00:00:00

  • Oxytocin/vasopressin-like immunoreactivity is present in the nervous system of hydra.

    abstract::Nerve cells have been found in hydra, which react with antisera to oxytocin, vasopressin and mesotocin. These nerve cells have a high density in the ectoderm of basal disk and tentacles and lower density in the ectoderm of peduncle, gastric region and hypostome. A very small number of nerve cells occur also in the end...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(82)90241-x

    authors: Grimmelikhuijzen CJ,Dierickx K,Boer GJ

    更新日期:1982-01-01 00:00:00

  • Altered distribution and levels of cathepsinD and cystatins in amyotrophic lateral sclerosis transgenic mice: possible roles in motor neuron survival.

    abstract::In amyotrophic lateral sclerosis (ALS) there is a selective degeneration of motor neurons leading to muscle paralysis and death. The mechanism underlying cell demise in ALS is not fully understood, but involves the activation of different proteolytic enzymes, including the caspase family of cysteine proteases. We have...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2006.07.048

    authors: Wootz H,Weber E,Korhonen L,Lindholm D

    更新日期:2006-12-01 00:00:00

  • Functional differences between D(1) and D(5) revealed by high resolution imaging on live neurons.

    abstract::The interaction between the dopaminergic and glutamatergic systems governs normal behavior and is perturbed in many psychiatric disorders including schizophrenia. Hypofunction of the D1 family of receptors, to which the D(1) and D(5) subtypes belong, is a typical feature of schizophrenia. Here we have used confocal li...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2009.08.052

    authors: Kruusmägi M,Kumar S,Zelenin S,Brismar H,Aperia A,Scott L

    更新日期:2009-12-01 00:00:00

  • Localization of dynorphin gene product-immunoreactivity in neurons from spinal cord and dorsal root ganglia.

    abstract::Using spinal cord and dorsal root ganglion cell cultures, we have studied the immuno-histochemical distribution of several peptide products of the dynorphin gene. With antibody directed toward the midregion of dynorphin A, peptide-immunoreactivity was found exclusively in the cell bodies of spinal cord neurons. Antibo...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(86)90110-7

    authors: Sweetnam PM,Wrathall JR,Neale JH

    更新日期:1986-08-01 00:00:00

  • Extracellular hydrogen ions influence channel-mediated and carrier-mediated K+ fluxes in cultured mouse astrocytes.

    abstract::Physiological (pH 7.2 and 7.0) and pathological (pH 6.8 and 6.6) changes of external pH, as they are measured in vivo, were imposed on mouse astrocytes in primary cultures and the effect on components of K+ transport pathways across the cell membrane was measured. Physiological pH changes had no effect at all. Patholo...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(87)90024-8

    authors: Walz W,Hinks EC

    更新日期:1987-01-01 00:00:00

  • Peri-infarct flow transients predict outcome in rat focal brain ischemia.

    abstract::Spreading depolarizations are accompanied by transient changes in cerebral blood flow (CBF). In a post hoc analysis of previously studied control rats we analyzed CBF time courses after middle cerebral artery occlusion in the rat in order to test whether intra-ischemic flow, reperfusion, and different parameters of pe...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2012.08.049

    authors: Lückl J,Dreier JP,Szabados T,Wiesenthal D,Bari F,Greenberg JH

    更新日期:2012-12-13 00:00:00

  • Calcium channels controlling acetylcholine release in the guinea-pig isolated anterior pelvic ganglion: an electropharmacological study.

    abstract::An electropharmacological analysis of the type(s) of calcium channel controlling neurotransmitter release in preganglionic sympathetic nerve terminals in the guinea-pig anterior pelvic ganglion has been carried out. Conventional intracellular recording techniques were used to record excitatory postsynaptic potentials ...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/s0306-4522(99)00286-9

    authors: Smith AB,Cunnane TC

    更新日期:1999-01-01 00:00:00

  • Distribution of calcitonin gene-related peptide in the rat peripheral nervous system with reference to its coexistence with substance P.

    abstract::This immunocytochemical study, using a double-staining method, showed that calcitonin gene-related peptide-like immunoreactive structures are widely distributed in the peripheral nervous system and that many of them coexist with substance P-like immunoreactive structures in single sensory ganglion cells. Neurons posit...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(85)90265-9

    authors: Lee Y,Takami K,Kawai Y,Girgis S,Hillyard CJ,MacIntyre I,Emson PC,Tohyama M

    更新日期:1985-08-01 00:00:00

  • Glutamatergic input-output properties of thalamic astrocytes.

    abstract::Astrocytes in the somatosensory ventrobasal (VB) thalamus of rats respond to glutamatergic synaptic input with metabotropic glutamate receptor (mGluR) mediated intracellular calcium ([Ca²⁺](i)) elevations. Astrocytes in the VB thalamus also release the gliotransmitter (GT) glutamate in a Ca²⁺-dependent manner. The tri...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2011.12.049

    authors: Pirttimaki TM,Parri HR

    更新日期:2012-03-15 00:00:00

  • Peripheral secretin-induced Fos expression in the rat brain is largely vagal dependent.

    abstract::I.v. injection of secretin activates neurons in brain areas controlling autonomic function and emotion. Peripheral administration of secretin inhibits gastric functions through a central mechanism that is mediated by vagal dependent pathways. We investigated whether the vagus nerve is involved in i.p. injection of sec...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2004.06.027

    authors: Yang H,Wang L,Wu SV,Tay J,Goulet M,Boismenu R,Czimmer J,Wang Y,Wu S,Ao Y,Taché Y

    更新日期:2004-01-01 00:00:00

  • Quantitative autoradiographic mapping of neurohypophysial hormone binding sites in the rat forebrain and pituitary gland--I. Characterization of different types of binding sites and their distribution in the Long-Evans strain.

    abstract::Oxytocin and vasopressin binding sites were localized and characterized by quantitative autoradiography on consecutive sections of Long-Evans rat forebrains and pituitary glands, incubated in the presence of 5 nM [3H]oxytocin or 5 nM [3H]vasopressin. In the forebrain, two types of neurohypophysial hormone binding site...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(88)90143-1

    authors: Freund-Mercier MJ,Stoeckel ME,Dietl MM,Palacios JM,Richard P

    更新日期:1988-07-01 00:00:00

  • Dimethyl fumarate attenuates 6-OHDA-induced neurotoxicity in SH-SY5Y cells and in animal model of Parkinson's disease by enhancing Nrf2 activity.

    abstract::Oxidative stress is central to the pathology of several neurodegenerative diseases, including Parkinson's disease (PD), and therapeutics designed to enhance antioxidant potential could have clinical value. In this study, we investigated whether dimethyl fumarate (DMF) has therapeutic effects in cellular and animal mod...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2014.11.047

    authors: Jing X,Shi H,Zhang C,Ren M,Han M,Wei X,Zhang X,Lou H

    更新日期:2015-02-12 00:00:00

  • Presynaptic effects of 4-aminopyridine and changes following a single giant impulse at the Torpedo nerve-electroplaque junction.

    abstract::The presynaptic changes caused by 4-aminopyridine were studied in the electric organ of Torpedo marmorata, in the resting state and during the period following transmission of a single giant discharge. Incubation with 4-aminopyridine provoked a 30-40% decrease in the density of synaptic vesicles in nerve terminals, an...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/0306-4522(87)90367-8

    authors: Parducz A,Dunant Y,Loctin F,Muller D,Garcia-Segura LM

    更新日期:1987-08-01 00:00:00

  • Carnosine-like immunoreactivity in astrocytes of the glial tubes and in newly-generated cells within the tangential part of the rostral migratory stream of rodents.

    abstract::In the nervous system, the aminoacylhistidine dipeptide carnosine (beta-alanyl-L-histidine) has been shown to be expressed in the olfactory receptor neurons and in brain astrocytes. Using immunocytochemical techniques, we report here a dense carnosine-like immunoreactivity in the subependymal layer of the rodent foreb...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/s0306-4522(97)00596-4

    authors: Peretto P,Bonfanti L,Merighi A,Fasolo A

    更新日期:1998-07-01 00:00:00

  • Simvastatin increases excitability in the hippocampus via a PI3 kinase-dependent mechanism.

    abstract::Simvastatin is an HMG-CoA reductase inhibitor commonly used in the clinic to treat hypercholesterolemia. In addition, simvastatin has been shown to cross the blood-brain barrier and pleiotropic effects of simvastatin have been reported including anti-inflammatory properties, enhancement of neurite outgrowth, and memor...

    journal_title:Neuroscience

    pub_type: 杂志文章

    doi:10.1016/j.neuroscience.2015.02.023

    authors: Métais C,Hughes B,Herron CE

    更新日期:2015-04-16 00:00:00