Abstract:
:M1 muscarinic receptors have long been identified as a potential therapeutic target for the treatment of cognitive impairment in Alzheimer's disease (AD). Our previous study has shown that M1 receptors promote membrane insertion and synaptic delivery of AMPA receptor GluA1 subunit. In this study, we sought to determine whether activation of M1 receptor would rescue the cognitive impairment in AD model mice through modulation of GluA1 subunit. For the mice injected with aggregated β-amyloid (Aβ) fragments to impair learning and memory, activation of M1 receptors could rescue it by reducing the latency to find the platform and spending more time in the target quadrant in the probe test in the Morris water maze. However, such an effect was ablated in mice with Ser845 residue of GluA1 mutated to alanine. Furthermore, the activation of M1 receptors enhanced the expression of GluA1 and its phosphorylation at Ser845 and drove GluA1 to incorporate with PSD95, a postsynaptic marker, in the hippocampi from Aβ-injected wild type mice but not from the mutant mice. Moreover, for 9-month-old APP/PS1 transgenic AD model mice, which may resemble the late AD, M1 receptor activation could not improve the cognitive impairment significantly. In addition, the enhancement of GluA1 expression and its phosphorylation at Ser845 were not observed in their hippocampi. Taken together, the study indicated that M1 receptor activation rescued the cognitive deficit through modulating the trafficking of GluA1-containing AMPA receptors and the therapeutics targeting M1 receptors should aim at mild AD or even pre-AD.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Zhao LX,Chen MW,Qian Y,Yang QH,Ge YH,Chen HZ,Qiu Ydoi
10.1016/j.neuroscience.2019.04.007subject
Has Abstractpub_date
2019-06-01 00:00:00pages
239-247eissn
0306-4522issn
1873-7544pii
S0306-4522(19)30247-7journal_volume
408pub_type
杂志文章相关文献
NEUROSCIENCE文献大全abstract::Intracellular recordings were made from neurones in myenteric ganglia of the guinea-pig ileum in vitro. Synaptic potentials were evoked by electrically stimulating presynaptic fibres as they entered the ganglion, using a small focal electrode. Slow synaptic depolarizations (excitatory postsynaptic potentials) were evo...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(85)90317-3
更新日期:1985-02-01 00:00:00
abstract::Glutamate is the most abundant excitatory neurotransmitter in the vertebrate central nervous system. It is widely assumed that neurons using this transmitter derive it from several sources: (i) synthesizing it themselves from alpha-ketoglutarate or aspartate, (ii) synthesize it from glial-derived glutamine, or (iii) t...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(94)90249-6
更新日期:1994-05-01 00:00:00
abstract::The postural, ocular motor, perceptive and neurovegetative syndromes resulting from unilateral vestibular neurectomy (UVN) symptoms could generate a stress and thereby activate the hypothalamo-pituitary-adrenal (HPA) axis. This study was aimed at determining whether UVN causes changes in the activity of the HPA axis, ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2009.02.070
更新日期:2009-06-02 00:00:00
abstract::The ontogeny of the cholecystokinin-8 neuron system in the lower brain stem of the rat was investigated by means of indirect immunofluorescence. Cholecystokinin-8-like immunoreactive structures first appeared in the primordium of the ventral tegmental area, ventral tegmental nucleus of Gudden and the area lateral to t...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(83)90116-1
更新日期:1983-12-01 00:00:00
abstract::We have reported that hypoxia affects the hypothalamic-pituitary-adrenal (HPA) axis and behavior by driving the expression of central corticotropin-releasing hormone (CRH) and its receptors in adult mammals, and this effect is modulated by other factors. Here, we address whether or not intermittent hypoxia (IH) or res...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2009.02.009
更新日期:2009-04-10 00:00:00
abstract::The hippocampus maintains the remarkable ability to generate new neurons throughout the lifespan. Progenitor cells in the subgranular zone give rise mainly to granule cells that migrate to the granule cell layer and become mature, functionally integrated neurons. Numerous factors are capable of regulating the prolifer...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2011.06.023
更新日期:2011-09-08 00:00:00
abstract::Hippocampal oscillations, particularly theta (6-12 Hz) and gamma (30-90 Hz) frequency bands, play an important role in several cognitive functions. Theta and gamma oscillations show cross-frequency coupling (CFC), wherein the phase of theta rhythm modulates the amplitude of the gamma oscillation, and this CFC is belie...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2019.05.053
更新日期:2019-08-01 00:00:00
abstract::Reversal learning is a domain that involves cognitive flexibility and is defined as the ability to rapidly alter established patterns of behavior when confronted with changing circumstances. This function depends critically on the orbitofrontal cortex (OFC) in the prefrontal cortical (PFC) structure, which is among th...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2010.08.037
更新日期:2010-11-10 00:00:00
abstract::The orexinergic neurons of the lateral hypothalamus (LH) are critical for wakefulness [McCarley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8:302-330]. Recent evidence suggests that adenosine (AD), a homeostatic sleep factor, may act via A1 receptor (A1R) to control orexinergic activity and regulate sleep-...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2008.01.017
更新日期:2008-06-02 00:00:00
abstract::A variety of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonists, and the antiepileptic drug lamotrigine, were examined for their ability to restore locomotion and other behaviours when injected stereotaxically via indwelling cannulae into the striatum or substantia n...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(96)00407-1
更新日期:1997-01-01 00:00:00
abstract::Perineuronal nets of extracellular matrix are associated with distinct types of neurons in the cerebral cortex and many subcortical regions. Large complexes of aggregating proteoglycans form a chemically specified microenvironment around the somata, proximal dendrites and the axon initial segment, including the presyn...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2005.11.068
更新日期:2006-01-01 00:00:00
abstract::In these experiments a large portion of the pelvic ganglion of adult female rats was transplanted into the wall of the urinary bladder of the same animals. The morphology and fine structure of the transplants were studied in whole-mounts and in sections for light and electron microscopy, from two days up to four month...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(97)00401-6
更新日期:1998-03-01 00:00:00
abstract::A new mammalian neuromuscular preparation is introduced for physiology and microscopy of all sorts: the intrinsic muscle of the mouse ear. The great utility of this preparation is demonstrated by illustrating how it has permitted us to develop a wholly new technique for staining muscle T-tubules, the critical conducti...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2019.07.028
更新日期:2020-07-15 00:00:00
abstract::Semi-quantitative immunocytochemistry was used to investigate the levels of cyclase response element-binding protein, phosphorylated cyclase response element-binding protein, Fos and Fos-related antigen immunoreactivity in the striatum of rats after acute or repeated amphetamine administration. Rats were perfused 20 m...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(95)00274-m
更新日期:1995-11-01 00:00:00
abstract::Subjective tinnitus is a chronic neurological disorder in which phantom sounds are perceived. Recent evidence supports the hypothesis that tinnitus is related to neuronal hyperactivity in auditory brain regions, and consequently drugs that increase GABAergic neurotransmission in the CNS, such as the GABA(B) receptor a...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2013.11.032
更新日期:2014-01-31 00:00:00
abstract::The midbrain is essential for prepulse inhibition (PPI) of the startle reflex, but the exact neural circuits for PPI are not yet determined. Electrical stimulation of the superior colliculus (SC) or pedunculopontine tegmentum was used to characterize the neurons and pathways that mediate PPI and the activation of star...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2006.06.025
更新日期:2006-11-03 00:00:00
abstract::Efferent projections of intrastriatally implanted striatal neurons have been studied using a combination of anterograde and retrograde axonal tracers. Adult rats subjected to a unilateral ibotenic acid lesion of the head of the caudate putamen received cell suspension grafts obtained from 14 15-day-old striatal primor...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(89)90256-x
更新日期:1989-01-01 00:00:00
abstract::Depolarization-induced transmitter release in synaptosomes prepared from the hippocampus of aged rats is decreased compared with release from young animals. Although the underlying cause of this deficit is not known, some evidence suggests that increased membrane rigidity may contribute to these age-related synaptic c...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(99)00219-5
更新日期:1999-01-01 00:00:00
abstract::Most functional imaging studies of memory retrieval investigate memory for standardized laboratory stimuli. However, naturally acquired autobiographical memories differ from memories of standardized stimuli in important ways. Neuroimaging studies of natural memories may reveal distinctive patterns of brain activation ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(01)00108-7
更新日期:2001-01-01 00:00:00
abstract::Nitric oxide is thought to play an important role in multiple forms of use-dependent synaptic plasticity, including that which follows noxious peripheral stimulation. This suggests that development of nociception-induced neuroplasticity should be impaired in transgenic animals lacking the neuronal form of nitric oxide...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(95)00395-y
更新日期:1995-12-01 00:00:00
abstract::Previous studies show that most short thoracic propriospinal (TPS; T5-T7) and long descending propriospinal tract (LDPT; C4-C6) neurons are lost following low-thoracic spinal cord contusion injury (cSCI), as assessed by retrograde labeling with fluorogold (FG). Gene microarray and terminal deoxynucleotidyl transferase...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2011.05.052
更新日期:2011-10-27 00:00:00
abstract::The difference in visual object recognition by males and females suggests a sex-specific function in the medial prefrontal cortex (mPFC). In the present study, we performed an in vivo microdialysis study in three groups of rats (males, diestrous females, and proestrous females) to examine the potential sex difference ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2008.12.039
更新日期:2009-03-03 00:00:00
abstract::Microglia, the primary immune cells in the brain, have been implicated as the predominant cells governing inflammation-mediated neuronal damage. In response to immunological challenges such as lipopolysaccharide (LPS), microglia are activated and subsequently inflammatory process is initiated as evidenced by the relea...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2014.09.034
更新日期:2014-12-05 00:00:00
abstract::Microelectrode recordings were made from 5-10 micron dia axons of adult rat spinal cord in vitro. Action potentials in response to electrical stimulation were recorded intracellularly and electrical characteristics of the axons were examined by injecting current pulses through a bridge circuit. All action potentials l...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(85)90118-6
更新日期:1985-05-01 00:00:00
abstract::Bone morphogenetic proteins (BMPs) are members of the transforming growth factor β (TGF-β) superfamily. BMPs, such as BMP2 and BMP4, exert its biological functions by interacting with membrane bound receptors belonging to the serine/threonine kinase family including bone morphogenetic protein receptor I (BMPRIA, BMPRI...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2011.12.022
更新日期:2012-02-17 00:00:00
abstract:OBJECTIVE:To examine the efficiency of hydrogen-rich saline in the treatment of intensive noise-induced cochlear injury. MATERIALS AND METHODS:Forty guinea pigs were assigned to one of four groups: HS+NOISE (i.p. injection hydrogen-rich saline), NS+NOISE (i.p. injection normal saline), NOISE ALONE (noise control), and...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2012.02.028
更新日期:2012-05-03 00:00:00
abstract::The influence of transient increases in adrenal steroid hormones on the number of Fos-positive neurons after nociceptor activation was assessed in adrenalectomized rats. Fos protein, the product of the immediate early gene, c-fos, was detected immunocytochemically within the spinal trigeminal nucleus 2 h after noxious...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(94)00624-e
更新日期:1995-06-01 00:00:00
abstract::The interconnectivity between brain development and the immune system has become an area of interest for many neuroscientists. However, to date, a limited number of known immune mediators of the peripheral nervous system (PNS) have been found to influence the development of the central nervous system (CNS). FOXP3 is a...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2020.06.032
更新日期:2020-08-21 00:00:00
abstract::Oscillatory activity is a prominent characteristic of electrophysiological recordings in the olfactory system and has been proposed to play a key role in encoding olfactory representations. Studies in several systems have shown that some aspects of information coding involve characteristics that intertwine spikes and ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2008.07.077
更新日期:2008-10-15 00:00:00
abstract::Using in vitro autoradiography, we investigated [3H] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, [3H]kainate and [3H]N-methyl-D-aspartate binding in two forebrain regions, the hippocampus and striatum, of young (four months of age) and aged (24-25 months of age) Long-Evans rats that had previously been teste...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(96)00147-9
更新日期:1996-10-01 00:00:00