Neuroprotection by nicotinamide mononucleotide adenylyltransferase 1 with involvement of autophagy in an aged rat model of transient cerebral ischemia and reperfusion.


:Recent researches suggest that autophagic degradation declines with age, and this leads to an accumulation of damage that contributes to age-related cellular dysfunction. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) shows therapeutic potential for cerebral ischemia in young-adult animals. This study investigated the role of NMNAT1 in focal cerebral ischemia in aged rats with a focus on neuronal autophagy. Focal cerebral ischemia was induced in aged rats by middle cerebral artery occlusion (MCAO). NMNAT1 levels in the peri-infarct penumbra increased at 12 and 24 h after ischemia in aged rats. Knockdown of NMNAT1 significantly increased infarct volume, whereas overexpression of NMNAT1 reduced ischemia-induced cerebral injuries in aged rats with acute ischemic stroke. Meanwhile, lentiviral overexpression of NMNAT1 increased autophagy, reduced the phosphorylation of mammalian target of rapamycin (mTOR), and enhanced the sirtuin 1 (SIRT1) protein level. In cultured cortical neurons, SIRT1 regulated the mTOR-mediated autophagy upon oxygen-glucose deprivation (OGD) stress and the effect of NMNAT1 on autophagy was blocked in cultured SIRT1-knockout neurons. Furthermore, autophagy inhibitor 3-methyladenine (3-MA) partly abolished the neuroprotection induced by NMNAT1 overexpression. The results suggest NMNAT1 protects against acute ischemic stroke in aged rats by inducing autophagy via regulating the SIRT1/mTOR pathway.


Brain Res


Brain research


Wang P,Lu Y,Han D,Wang P,Ren L,Bi J,Liang J




Has Abstract


2019-11-15 00:00:00












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    journal_title:Brain research

    pub_type: 杂志文章


    authors: Watanabe T,Morimoto K,Nakamura M,Hirao T,Ninomiya T,Ando N,Suwaki H

    更新日期:2004-04-02 00:00:00

  • A monoclonal antibody to mammalian neurofilament protein stains somata and dendrites in gymnotid fish.

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    journal_title:Brain research

    pub_type: 杂志文章


    authors: Maler L,Leclerc N,Hawkes R

    更新日期:1986-07-23 00:00:00

  • Regulation of nestin expression after cortical ablation in adult rat brain.

    abstract::During embryogenesis, transient expression of nestin in proliferating neuroepithelial stem cells signals the commitment of progenitor cells to differentiate. Although adult mammalian brain contains very little nestin, significant upregulation of nestin has been reported following cerebral injury, leading to speculatio...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Douen AG,Dong L,Vanance S,Munger R,Hogan MJ,Thompson CS,Hakim AM

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  • Electron microscopic localization of acetylcholinesterase in the dentate gyrus of young and adult rats.

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    journal_title:Brain research

    pub_type: 杂志文章


    authors: Seress L,Robertson RT,Ribak CE

    更新日期:1987-11-01 00:00:00

  • In vivo measurement of a diurnal variation in vasopressin release in the rat suprachiasmatic nucleus.

    abstract::Diurnal changes in the intranuclear release of vasopressin (VP) and oxytocin (OT) in the suprachiasmatic (SCN), paraventricular (PVN) and supraoptic nuclei (SON) of the rat were studied by means of brain microdialysis. A significant diurnal variation in VP release in the SCN was detected, with the highest levels occur...

    journal_title:Brain research

    pub_type: 杂志文章


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  • Alterations of serotonin synaptic proteins in brain regions of neonatal Rhesus monkeys exposed to perinatal environmental tobacco smoke.

    abstract::Serotonin (5HT) systems play important roles in brain development, and early perturbations of 5HT receptor expression produce permanent changes in 5HT synaptic function and associated behaviors. We exposed pregnant Rhesus monkeys to environmental tobacco smoke (ETS) during gestation and for up to 3 months postnatally ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Slotkin TA,Pinkerton KE,Tate CA,Seidler FJ

    更新日期:2006-09-21 00:00:00

  • CCK8 neurons of the ventromedial (VMH) hypothalamus mediate the upper gut motor changes associated with feeding in rats.

    abstract::The effect of microinfusions of cholecystokinin octapeptide (CCK8) and its antagonist L364,718 on duodenal and jejunal motility were evaluated by electromyography in fasted and fed rats. The rats were chronically fitted with electrodes implanted on the duodeno-jejunal wall. Steel cannulas were placed bilaterally in ei...

    journal_title:Brain research

    pub_type: 杂志文章


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  • Effects of handling on extracellular levels of glutamate and other amino acids in various areas of the brain measured by microdialysis.

    abstract::Upon a physiological and pharmacological challenge, the responsiveness of extracellular glutamate levels in the prefrontal cortex, ventral tegmental area and locus coeruleus were studied using microdialysis. A 10-min handling period was used as a mild stressful stimulus. In all three brain areas, handling induced an i...

    journal_title:Brain research

    pub_type: 杂志文章


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  • The 5HT1A receptor agonist, 8-OH-DPAT, protects neurons and reduces astroglial reaction after ischemic damage caused by cortical devascularization.

    abstract::Serotonin 1A (5HT1A) receptor agonists have shown neuroprotective properties in different models of central nervous system injury. Activation of neuronal 5HT1A receptors appears to be involved in the neuroprotective effects. It remains to be elucidated if astroglial cells are responsive to the 5HT1A neuroprotective ef...

    journal_title:Brain research

    pub_type: 杂志文章


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  • Glucosylceramide synthase decrease in frontal cortex of Alzheimer brain correlates with abnormal increase in endogenous ceramides: consequences to morphology and viability on enzyme suppression in cultured primary neurons.

    abstract::Abnormal increase in native long-chain ceramides (lcCer) in AD implicates roles in neuronal atrophy and cognitive dysfunction especially in view of divergent roles this second messenger plays in cell function. Since clearance is mediated by glucosylceramide synthase (GCS, EC levels of the enzyme were compare...

    journal_title:Brain research

    pub_type: 杂志文章


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  • Anatomical organization of retinotectal afferents in the cat: an autoradiographic study.

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    journal_title:Brain research

    pub_type: 杂志文章


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  • In vivo and in vitro effects of proline on some parameters of oxidative stress in rat brain.

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    journal_title:Brain research

    pub_type: 杂志文章


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    journal_title:Brain research

    pub_type: 杂志文章


    authors: Graham WC,Crossman AR,Woodruff GN

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  • Colocalization of D1 and D2 dopamine receptor mRNAs in striatal neurons.

    abstract::There is evidence that D1 and D2 dopamine receptor subtypes coexist at the cellular level in the striatum and act synergistically to mediate the effects of dopamine. Other data suggest that these receptor subtypes are largely segregated in different striatal projection pathways. We used in situ hybridization in serial...

    journal_title:Brain research

    pub_type: 杂志文章


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    更新日期:1993-09-03 00:00:00

  • COA-Cl induces dopamine release and tyrosine hydroxylase phosphorylation: In vivo reverse microdialysis and in vitro analysis.

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    journal_title:Brain research

    pub_type: 杂志文章


    authors: Jamal M,Tsukamoto I,Takata M,Ito A,Tanaka N,Miki T,Takakura A,Ameno K,Kubota Y,Konishi R,Kinoshita H

    更新日期:2019-03-01 00:00:00

  • Magnolol and honokiol prevent learning and memory impairment and cholinergic deficit in SAMP8 mice.

    abstract::The therapeutic use of neurotrophic factors to treat neurodegenerative disorders, including Alzheimer's disease, is considered feasible. Magnolol and honokiol, constituents of the Magnolia plant, are small organic compounds with neurotrophic activity. We investigated whether magnolol and honokiol can prevent age-relat...

    journal_title:Brain research

    pub_type: 杂志文章


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    journal_title:Brain research

    pub_type: 杂志文章


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    更新日期:2000-01-03 00:00:00

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    abstract::We have previously demonstrated that ibotenate (IBO)-stimulated polyphosphoinositide (PPI) hydrolysis is increased for a long period in the amygdala/pyriform cortex (AM/PC) of amygdala (AM)- and hippocampal (HIPP)-kindled rats. This finding indicates that enhanced function of the PPI-coupled excitatory amino acid (EAA...

    journal_title:Brain research

    pub_type: 杂志文章


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    更新日期:1992-01-08 00:00:00

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    abstract::The existence of multiple brain melanocortin receptor types has been postulated, based on the complex pharmacology of intracerebrally administered melanocortin (melanocyte-stimulating hormone-related) peptides. In this study, this hypothesis was tested by determining whether different brain melanocortin receptor popul...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Tatro JB,Entwistle ML

    更新日期:1994-01-28 00:00:00

  • Signalling pathways in the nitric oxide donor-induced dopamine release in the striatum of freely moving rats: evidence that exogenous nitric oxide promotes Ca2+ entry through store-operated channels.

    abstract::We showed previously, using in vitro microdialysis, that the activation of the soluble guanylate cyclase (sGC)/cyclic GMP pathway was the underlying mechanism of the extracellular Ca(2+)-dependent effects of exogenous NO on dopamine (DA) secretion from PC12 cells. In this study, the co-infusion of the sGC inhibitor 1H...

    journal_title:Brain research

    pub_type: 杂志文章


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  • Fibrous astrocytes and reactive astrocyte-like cells in transplants of cultured astrocyte precursor cells.

    abstract::Mouse neopallium was disaggregated at 3 developmental stages (E15, E18, PO) and grown in colony cultures for 7 days. On the seventh day of culturing the colonies of cells were transplanted into the cerebellums of neonatal mice. After 3 weeks the astrocytes within the transplants were identified with GFAP immunoperoxid...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Doering LC,Fedoroff S,Devon RM

    更新日期:1983-01-01 00:00:00

  • Ultrastructural damage and neuritic beading in cold-stressed spinal neurons with comparisons to NMDA and A23187 toxicity.

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    journal_title:Brain research

    pub_type: 杂志文章


    authors: Emery DG,Lucas JH

    更新日期:1995-09-18 00:00:00

  • Phosphodiesterase 4B (PDE4B) and cAMP-level regulation within different tissue fractions of rat hippocampal slices during long-term potentiation in vitro.

    abstract::Molecular events associated with mnemonic processes and neuronal plasticity are postulated to result in functional changes in synaptic structure. One possible site is the post-synaptic density, where activity-dependent changes modulate signal transduction cascades. In this report, we detail spatial-temporal changes fo...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Ahmed T,Frey JU

    更新日期:2005-04-18 00:00:00

  • Central angiotensin III-induced dipsogenicity in rats and gerbils.

    abstract::Previous findings from our laboratory demonstrated [125I]angiotensin II (AII) binding to plasma membranes from rat but not gerbil circumventricular organs (CVOs), the presumed location of brain receptors for angiotensin-induced dipsogenicity. Since members of both species drink to intracranially applied AII, a degrada...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Wright JW,Morseth S,Mana MJ,LaCrosse E,Petersen EP,Harding JW

    更新日期:1984-03-12 00:00:00

  • Long-term potentiation in the dentate gyrus is preferentially induced at theta rhythm periodicity.

    abstract::In urethane-anesthetized rats, high frequency stimulation was applied to the medial perforant pathway at various time intervals (50, 100, 200, 350 and 500 ms) following stimulation of the same pathway by a single pulse of equal intensity. Recordings of dentate gyrus granule cell evoked responses were made to investiga...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Greenstein YJ,Pavlides C,Winson J

    更新日期:1988-01-12 00:00:00

  • Apamin, a blocker of the calcium-activated potassium channel, induces neurodegeneration of Purkinje cells exclusively.

    abstract::Following acute intracerebroventricular injections of 1 ng of apamin and chronic apamin infusion (0.4 ng/microl, 0.5 microl/h, 14 days), the rat brains exhibited bilateral damage only in the cerebellum. The argyrophilic cells were Purkinje cells in copula pyramis, flocculus, paraflocculus, and paramedian lobules. Thes...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Mourre C,Fournier C,Soumireu-Mourat B

    更新日期:1997-12-19 00:00:00

  • Excitation of Limulus photoreceptors by hydrolysis-resistant analogs of cGMP and cAMP.

    abstract::cGMP was proposed to be the agent which directly opens the light-sensitive channel in Limulus ventral photoreceptors. However, the light-sensitive rhabdomeral-lobe (R-lobe) is not uniformly responsive to cGMP injection; that is, there are 'hot spots' of sensitivity. A potent phosphodiesterase which rapidly hydrolyses ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Feng JJ,Frank TM,Fein A

    更新日期:1991-06-28 00:00:00

  • VIP-like immunoreactivity in the anterior hypothalamic area of a hibernating bat varies with physiological state.

    abstract::Vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the anterior hypothalamic area (AHA) was studied in 15 bats which are seasonal hibernators, using the unlabeled antibody enzyme method of Sternberger. Our results showed that the density of immunoreactive fibers and terminal plexuses in the AHA was great...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Laemle LK,Cotter JR

    更新日期:1988-02-16 00:00:00

  • Metabolic inhibition potentiates AMPA-induced Ca2+ fluxes and neurotoxicity in rat cerebellar granule cells.

    abstract::The effects of partial metabolic inhibition (induced by 2 h exposure to low concentrations of cyanide (NaCN)) on the glutamate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-induced excitotoxicity and elevation of free cytoplasmic Ca2+ levels ([Ca2+]i) were studied in glucose-deprived pri...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Cebers G,Cebere A,Liljequist S

    更新日期:1998-01-01 00:00:00

  • Involvement of M1 muscarinic receptors in the initiation of cholinergically induced epileptic seizures in the rat brain.

    abstract::The present study was designed to determine the types of acetylcholine receptors involved in the initiation of epileptic seizures from the zona incerta and surrounding structures by cholinergic stimulation in rats. Unilateral intracerebral microinjection of the mixed muscarinic and nicotinic agonist carbachol (3 micro...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Cruickshank JW,Brudzynski SM,McLachlan RS

    更新日期:1994-04-18 00:00:00