Abstract:
:The dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis is often seen in Alzheimer's disease (AD) patients with cognitive deficits. Selective inhibition of phosphodiesterase (PDE) 4 and 5 has already proven to be effective in reducing beta-amyloid 1-42 (Aβ1-42)-mediated pathology by regulating corticotropin-releasing factor (CRF) and glucocorticoid receptor (GR) expression, suggesting that PDE-dependent signaling is involved in Aβ1-42-induced HPA axis dysfunction. However, nausea and vomiting are the side effects of some PDE4 inhibitors, which turn our attention to other PDEs. PDE2 are highly expressed in the hippocampus and cortex, which associate with learning and memory, but not in the area postrema that would cause vomiting. The present study suggested that microinjection of Aβ1-42 to the intracerebroventricle induced learning and memory impairments and dysregulation of the HPA axis by increased expression of CRF and GR. However, the PDE2 inhibitor Bay 60-7550 significantly ameliorated the learning and memory impairment in the Morris water maze (MWM) and step-down passive avoidance tests. The Aβ1-42-induced increased CRF and GR levels were also reversed by the treatment with Bay 60-7550. These Bay 60-7550's effects were prevented by pretreatment with the PKG inhibitor KT5823. Moreover, the Bay 60-7550-induced downstream phosphorylation of cyclic AMP response element binding (pCREB) and brain-derived neurotrophic factor (BDNF) expression was also prevented (or partially prevented) by KT5823 or the PKA inhibitor H89. These results may lead to the discovery of novel strategies for the treatment of age-related cognitive disorders, such as AD, which affects approximately 44 million people worldwide.
journal_name
Front Cell Neuroscijournal_title
Frontiers in cellular neuroscienceauthors
Ruan L,Du K,Tao M,Shan C,Ye R,Tang Y,Pan H,Lv J,Zhang M,Pan Jdoi
10.3389/fncel.2019.00432subject
Has Abstractpub_date
2019-10-02 00:00:00pages
432issn
1662-5102journal_volume
13pub_type
杂志文章abstract::Neurosteroids are cholesterol-based hormones that can be produced in the brain, independent of secretion from peripheral endocrine glands, such as the gonads and adrenals. A focus in our laboratory for over 25 years has been how production of the pregnane neurosteroid, allopregnanolone, is regulated and the novel (i.e...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2014.00106
更新日期:2014-04-09 00:00:00
abstract::Chronic inflammation and oxidative stress (OS) are present in Alzheimer's disease (AD) brains in addition to neuronal loss, Amyloid-β (Aβ) plaques and hyperphosphorylated tau-protein neurofibrillary tangles (NFTs). Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18 (IL-18), are elevated ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00214
更新日期:2014-08-07 00:00:00
abstract::Brain neurons, to support their neurotransmitter functions, require a several times higher supply of glucose than non-excitable cells. Pyruvate, the end product of glycolysis, through pyruvate dehydrogenase complex reaction, is a principal source of acetyl-CoA, which is a direct energy substrate in all brain cells. Se...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2018.00169
更新日期:2018-07-10 00:00:00
abstract::Cells under stress activate cell survival and cell death signaling pathways. Cell death signaling frequently converges on mitochondria, a process that is controlled by the activities of pro- and anti-apoptotic B-cell lymphoma 2 (BCL-2) proteins. In this review, we summarize current knowledge on the control of neuronal...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2014.00281
更新日期:2014-09-30 00:00:00
abstract::Binge-drinking is the most prevalent form of alcohol abuse and while an early life history of binge-drinking is a significant risk factor for subsequent alcoholism and co-morbid affective disorders, relatively little is known regarding the biobehavioral impact of binge-drinking during the sensitive neurodevelopmental ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2016.00265
更新日期:2016-11-18 00:00:00
abstract::Stress affects brain areas involved in learning and emotional responses, which may contribute in the development of cognitive deficits associated with major depression. These effects have been linked to glial cell activation, glutamate release and changes in neuronal plasticity and survival including atrophy of hippoc...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00102
更新日期:2015-04-02 00:00:00
abstract::An experience-driven increase in oligodendrocytes and myelin in the somatosensory cortex (S1) has emerged as a new marker of adult cortical plasticity. That finding contrasts with the view that myelin is a structural brake on plasticity, and that contributes to ending the critical period (CP) in the visual cortex (V1)...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2020.00056
更新日期:2020-03-17 00:00:00
abstract:Background:The functional aspects of mast cell-microglia interactions are important in neuroinflammation. Our previous studies have demonstrated that mast cell degranulation can directly induce microglia activation. However, the role of mast cells in Lipopolysaccharide (LPS)-induced microglia activation, neuroinflammat...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00191
更新日期:2019-05-03 00:00:00
abstract::Neurodegenerative diseases in general and specifically late-onset Alzheimer's disease (LOAD) involve a genetically complex and largely obscure ensemble of causative and risk factors accompanied by complex feedback responses. The advent of "high-throughput" transcriptome investigation technologies such as microarray an...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00089
更新日期:2014-03-27 00:00:00
abstract::Amyloid beta (Aβ) is a peptide cleaved from amyloid precursor protein that contributes to the formation of senile plaques in Alzheimer's disease (AD). The relationship between Aβ and astrocyte proliferation in AD remains controversial. Despite pathological findings of increased astrocytic mitosis in AD brains, in vitr...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2017.00301
更新日期:2017-09-26 00:00:00
abstract::Major depressive disorder (MDD) is a mood disorder of multifactorial origin affecting millions of people worldwide. The alarming estimated rates of prevalence and relapse make it a global public health concern. Moreover, the current setback of available antidepressants in the clinical setting is discouraging. Therefor...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00268
更新日期:2015-07-10 00:00:00
abstract::Bone marrow-derived mononuclear cells (BM-MNCs) were shown to improve the outcome in animal stroke models and clinical pilot studies on BM-MNCs for stroke patients were already conducted. However, relevant aspects of pre-clinical evaluation, such as the use of animals with comorbidities and dose-response studies, were...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2013.00288
更新日期:2014-01-08 00:00:00
abstract::During pregnancy, a decreased availability of zinc to the fetus can disrupt the development of the central nervous system leading to defects ranging from severe malformations to subtle neurological and cognitive effects. We previously found that marginal zinc deficiency down-regulates the extracellular signal-regulate...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00062
更新日期:2019-03-01 00:00:00
abstract:PURPOSE:Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00484
更新日期:2015-12-22 00:00:00
abstract::Meningioma expressed antigen 6 (MEA6), also called cutaneous T cell lymphoma-associated antigen 5 (cTAGE5), was initially found in tumor tissues. MEA6 is located in endoplasmic reticulum (ER) exit sites and regulates the transport of collagen, very low density lipoprotein, and insulin. It is also reported that MEA6 mi...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00250
更新日期:2019-06-11 00:00:00
abstract::Regulatory T cells (Tregs) play an anti-inflammatory effect to protect against ischemic stroke. Plasmacytoid dendritic cells (pDCs) can induce regulatory T cells tolerance in sterile-inflammation conditions. However, whether and how pDCs-mediated Tregs response play a part in the pathology of ischemic stroke remains u...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2020.00008
更新日期:2020-01-31 00:00:00
abstract::Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are believed to represent the different outcomes of a common pathogenic mechanism. However, while researchers have intensely studied the involvement of motor neurons in the ALS/FTD syndrome, very little is known about the function of hippocampal neu...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2016.00216
更新日期:2016-09-20 00:00:00
abstract::From the VGF precursor protein originate several low molecular weight peptides, whose distribution in the brain and blood circulation is not entirely known. Among the VGF peptides, those containing the N-terminus portion were altered in the cerebro-spinal fluid (CSF) and hypothalamus of schizophrenia patients. "Hence,...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2017.00158
更新日期:2017-06-02 00:00:00
abstract::Since monumental studies from scientists like His, Ramón y Cajal, Lorente de Nó and many others have put down roots for modern neuroscience, the scientific community has spent a considerable amount of time, and money, investigating any possible aspect of the evolution, development and function of neurons. Today, the c...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2014.00201
更新日期:2014-07-28 00:00:00
abstract::The possible cognitive effects of low frequency external electric fields (EFs), such as those generated by power lines, are poorly understood. Their functional consequences for mechanisms at the single neuron level are very difficult to study and identify experimentally, especially in vivo. The major open problem is t...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00310
更新日期:2014-10-09 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-β (Aβ) plaques and the formation of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. In response to Aβ and tau aggregates, microglia, the primary innate immune cells of the central nervous system (CNS), facilitate Aβ a...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2020.563446
更新日期:2020-09-18 00:00:00
abstract::Objective: DL-3n-butylphthalide (NBP) has beneficial effects in different stages of ischemic stroke. Our previous studies have demonstrated that NBP promoted angiogenesis in the perifocal region of the ischemic brain. However, the molecular mechanism of NBP for blood-brain barrier protection in acute ischemic stroke w...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2020.610714
更新日期:2021-01-12 00:00:00
abstract::The blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB) form the barriers of the brain. These barriers are essential not only for the protection of the brain, but also in regulating the exchange of cells and molecules in and out of the brain. The choroid plexus (CP) epithelial cells and the ara...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00136
更新日期:2015-04-13 00:00:00
abstract::Oligodendrocytes are the myelinating cells of the central nervous system (CNS). While the phrase is oft repeated and holds true, the last few years have borne witness to radical change in our understanding of this unique cell type. Once considered static glue, oligodendrocytes are now seen as plastic and adaptive, cap...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00340
更新日期:2015-09-01 00:00:00
abstract::Ischemic stroke is a debilitating disease for which there are currently no effective treatments besides the clot-buster, tissue plasminogen activator (t-PA), which is administered to less than 10% of patients due to a limited (4.5 h) time window of efficacy. Thus, there is an urgent need for novel therapies that can p...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2012.00066
更新日期:2013-01-17 00:00:00
abstract::The striatum is a key structure for movement control, but the mechanisms that dictate the output of distinct subpopulations of medium spiny projection neurons (MSNs), striatonigral projecting and dopamine D1 receptor- (D1+) or striatopallidal projecting and dopamine D2 receptor- (D2+) expressing neurons, remains poorl...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2011.00015
更新日期:2011-07-28 00:00:00
abstract::Increasing evidence suggest that astrocytes significantly modulate neuronal function at the level of the tripartite synapse both in physiological and pathophysiological conditions. The global control of the astrocytic syncytium over neuronal networks, however, is still less recognized. Here we examined astrocytic sign...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00215
更新日期:2015-06-18 00:00:00
abstract::The hippocampal mossy fibers (MFs), the axons of the granule cells (GCs) of the dentate gyrus, innervate mossy cells and interneurons in the hilus on their way to CA3 where they innervate interneurons and pyramidal cells. Synapses on each target cell have distinct anatomical and functional characteristics. In recent y...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2013.00210
更新日期:2013-11-22 00:00:00
abstract::The anterior cingulate cortex (ACC) is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging t...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00107
更新日期:2018-04-20 00:00:00
abstract::Hair cells in the inner ear convert mechanical stimuli provided by sound waves and head movements into electrical signal. Several mechanically evoked ionic currents with different properties have been recorded in hair cells. The search for the proteins that form the underlying ion channels is still in progress. The me...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2018.00100
更新日期:2018-04-11 00:00:00