Abstract:
:Although the pathogenesis of Alzheimer's disease (AD) remains unclear, some molecular aspects that precede or accompany the deposit of β-amyloid in senile plaques attract attention, such as calcium dysregulation and neuroinflammation. It has been suggested that the Ca2+/calmodulin-dependent protein phosphatase, calcineurin (CaN), plays an important role in AD pathogenesis. We hypothesized that CaN activation is involved in the inflammatory changes observed in the streptozotocin (STZ)-induced model of AD. We investigated hippocampal inflammatory and CaN changes in Wistar rats in two moments after intracerebroventricular STZ administration: in the first week (early) and fourth week (later on). We found an early (at 1 week) and persistent (at fourth week) increment in the subunit A of CaN, as well as an increase in the major 48 kDa fragment of this subunit. Glial and inflammatory activation were confirmed by changes of IBA-1, TLR-4, glial fibrillary acidic protein (GFAP), and S100B in the hippocampus. Augmented CaN activity was accompanied by reduced phosphorylation of the pro-apoptotic protein BAD, at Ser 136. Importantly, we found an increase in the nuclear translocation of NFAT4 (more associated to astroglial reactivity) in the hippocampus at 1 and 4 weeks in this model. NFAT3 (more associated with neuronal activation) exhibited an early increase, but decreased later on. Taken together, these data contribute to the understanding of neurochemical changes in the STZ model of sporadic AD, and may explain the persistent inflammatory response in AD, which might occur via the proteolytic activation of CaN, and signaling of NFAT mediated by isoform 4, in activated astrocytes.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Dos Santos JPA,Vizuete AF,Gonçalves CAdoi
10.1007/s12035-019-01718-2subject
Has Abstractpub_date
2020-01-01 00:00:00pages
502-512issue
1eissn
0893-7648issn
1559-1182pii
10.1007/s12035-019-01718-2journal_volume
57pub_type
杂志文章abstract::The glutamate N-methyl-D-aspartate receptor (NMDAR) plays an essential role in the excitotoxic neural damage that follows ischaemic stroke. Because the sigma-1 receptor (σ1R) can regulate NMDAR transmission, exogenous and putative endogenous regulators of σ1R have been investigated using animal models of ischaemic str...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0697-x
更新日期:2018-06-01 00:00:00
abstract::Reelin is an extracellular glycoprotein involved in key cellular processes in developing and adult nervous system, including regulation of neuronal migration, synapse formation, and plasticity. Most of these roles are mediated by the intracellular phosphorylation of disabled-1 (Dab1), an intracellular adaptor molecule...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0177-8
更新日期:2017-10-01 00:00:00
abstract::Synaptic vesicle proton V-ATPase is an essential component in synaptic vesicle function. Active acidification of synaptic vesicles, triggered by the V-ATPase, is necessary for neurotransmitter storage. Independently from its proton transport activity, an additional important function of the membrane-embedded sector of...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1324-1
更新日期:2019-05-01 00:00:00
abstract::Retinoid X-receptors (RXRs) are members of the ligand-dependent transcription factor family of nuclear receptors that have gained recent research focus as potential targets for neurodegenerative disorders. Bexarotene is an RXR pharmacological agonist that is shown to be neuroprotective through its effects in promoting...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1041-9
更新日期:2018-12-01 00:00:00
abstract::An increasing number of circulating micro-ribonucleic acids (microRNAs, miRNAs) have been discovered its potential as biomarkers to diagnose neurodegenerative diseases (NDs) by many researchers. However, there were obvious inconsistencies among previous studies, and thus we performed this meta-analysis to evaluate whe...
journal_title:Molecular neurobiology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s12035-014-8944-x
更新日期:2015-12-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common cause of dementia among elderly people. Despite enormous efforts, the pathogenesis of AD still remains unclear and no drug has yet been proved to be disease-modifying. As the basis of learning and memory, the plasticity of synapse and dendritic spine has been impaired during...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02183-y
更新日期:2020-11-03 00:00:00
abstract::Our previous studies showed that intravenous immunoglobulin (IVIG) contained anti-Aβ autoantibodies that might be able to treat Alzheimer's disease (AD). Recently, we identified and characterized naturally occurring autoantibodies against PrP from IVIG. Although autoantibodies in IVIG blocked PrP fibril formation and ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1228-0
更新日期:2019-04-01 00:00:00
abstract::Sphingosine-1-phosphate (S1P) produced by sphingosine kinases (SPHK1 and SPHK2) is a signaling molecule involved in cell proliferation and formation of cellular junctions. In this study, we characterized the retinas of Sphk1 knockout (KO) mice by electron microscopy and immunocytochemistry. We also tested cultured Mül...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-1599-x
更新日期:2019-10-01 00:00:00
abstract::Involvement of membrane mineralocorticoid (MC) and glucocorticoid (GC) receptors in synaptic Zn2+ dynamics remains unclear. Here, we tested whether synaptic plasticity is affected by rapid intracellular Zn2+ dysregulation via membrane MC and GC receptor activation, in comparison with intracellular Ca2+ dysregulation. ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1159-9
更新日期:2019-02-01 00:00:00
abstract::Cannabidiol (CBD), one of the most abundant Cannabis sativa-derived compounds, has been implicated with neuroprotective effect in several human pathologies. Until now, no undesired side effects have been associated with CBD. In this study, we evaluated CBD's neuroprotective effect in terminal differentiation (mature) ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-014-8843-1
更新日期:2015-08-01 00:00:00
abstract::Parkinson's disease is a neurodegenerative disorder accompanied by depletion of dopamine and loss of dopaminergic neurons in the brain that is believed to be responsible for the motor and non-motor symptoms in this disease. The main drug prescribed for Parkinsonian patients is L-dopa, which can be converted to dopamin...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-018-1419-8
更新日期:2019-07-01 00:00:00
abstract::In neurodegenerative diseases, pathogenic proteins tend to misfold and form aggregates that are difficult to remove and able to induce excessive endoplasmic reticulum (ER) stress, leading to neuronal injury and apoptosis. Homocysteine-induced endoplasmic reticulum protein (Herp), an E3 ubiquitin ligase, is an importan...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-0900-8
更新日期:2018-10-01 00:00:00
abstract::The identification of causative mutations in the (pro)granulin gene (GRN) has been a major breakthrough in the research on frontotemporal dementia (FTD). So far, all FTD-associated GRN mutations are leading to neurodegeneration through a "loss-of-function" mechanism, encouraging researchers to develop a growing number...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-012-8380-8
更新日期:2013-02-01 00:00:00
abstract::The connection between the endocannabinoid system (ECS) and schizophrenia is supported by a large body of research. The ECS is composed of two types cannabinoid (CB: CB1 and CB2) receptors and their endogenous ligands, endocannabinoids. The best-known endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-1596-0
更新日期:2019-11-01 00:00:00
abstract::Protein aggregation is involved in a variety of diseases. Alteration of the aggregation pathway, either to produce less toxic structures or to increase aggregate clearance, is a promising therapeutic route. Both active and passive immunization has been used for this purpose. However, the mechanism of action of antibod...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9148-8
更新日期:2016-04-01 00:00:00
abstract::Neuronal plasticity can be defined as adaptive changes in structure and function of the nervous system, an obvious example of which is the capacity to remember and learn. Long-term potentiation and long-term depression are the experimental models of memory in the central nervous system (CNS), and have been frequently ...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02802028
更新日期:1998-01-01 00:00:00
abstract::Germline and somatic mutations in key genes of the mammalian target of rapamycin (mTOR) pathway have been identified in seizure-associated disorders. mTOR mutations lead to aberrant activation of mTOR signaling, and, although affected neurons are critical for epileptogenesis, the role of mTOR activation in glial cells...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9590-7
更新日期:2017-01-01 00:00:00
abstract::Clinical studies demonstrated a positive correlation between hypertension and cognitive decline. Beneficial effects of angiotensin II receptor blockers on cognitive functions have also been reported earlier; however, its role in chronic neuroinflammation-induced memory impairment in the hypertensive state is not well ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0450-5
更新日期:2018-02-01 00:00:00
abstract::Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NS...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9225-z
更新日期:2016-05-01 00:00:00
abstract::A random-sequence peptide microarray can interrogate serum antibodies in a broad, unbiased fashion to generate disease-specific immunosignatures. This approach has been applied to cancer detection, diagnosis of infections, and interrogation of vaccine response. We hypothesized that there is an immunosignature specific...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1354-8
更新日期:2019-06-01 00:00:00
abstract::There is accumulating evidence on the use of N-acetylcysteine (NAC) in the treatment of patients with neuropsychiatric disorders. As a multi-target drug and a glutathione precursor, NAC is a promising molecule in the management of stress-related disorders, for which there is an expanding field of research investigatin...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1165-y
更新日期:2019-02-01 00:00:00
abstract::Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem of vertebrates. Glycine is accumulated into synaptic vesicles by a proton-coupled transport system and released to the synaptic cleft after depolarization of the presynaptic terminal. The inhibitory action of glycine is mediated by pentame...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02740653
更新日期:1997-06-01 00:00:00
abstract::Classical galactosemia is an inborn error of carbohydrate metabolism in which patients accumulate high concentration of galactose in the brain. The most common treatment is a galactose-restricted diet. However, even treated patients develop several complications. One of the most common symptoms is motor coordination i...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9981-4
更新日期:2017-08-01 00:00:00
abstract::The original version of this article unfortunately contained mistake in its Funding inforation. ...
journal_title:Molecular neurobiology
pub_type: 已发布勘误
doi:10.1007/s12035-018-1095-8
更新日期:2018-10-01 00:00:00
abstract::During development, neurons migrate to the cortex radially from periventricular germinative zones as well as tangentially from ganglionic eminences. The vast majority of cortical neurons settle radially in the cortical plate. Neuronal migration requires an exquisite regulation of leading edge extension, nuclear transl...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/MN:30:3:225
更新日期:2004-12-01 00:00:00
abstract::Tourette syndrome (TS) is a childhood-onset neurological disorder. To date, accurate TS diagnosis remains challenging due to its varied clinical expressions and dependency on qualitative description of symptoms. Therefore, identifying accurate and objective neuroimaging biomarkers may help improve early TS diagnosis. ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0519-1
更新日期:2018-04-01 00:00:00
abstract::Cell fate reprogramming makes possible the generation of new cell types from healthy adult cells to replace those lost or damaged in disease. Additionally, reprogramming patient cells into specific cell types allows for drug screening and the development of new therapeutic tools. Generation of new neurons is of partic...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-012-8277-6
更新日期:2012-06-01 00:00:00
abstract::This article reviews a lecture I was honored to present at the Leon Wolfe Symposium in Montreal on March 25, 2004. The lecture described my research career, which started with my interaction with Wolfe at the Montreal Neurological Institute as a postdoctoral fellow and research associate and was followed by additional...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/mn:32:1:019
更新日期:2005-08-01 00:00:00
abstract::Linoleic acid (LA, 18:2n-6) is a precursor to arachidonic acid (AA, 20:4n-6), which can be converted by brain lipoxygenase and cyclooxygenase (COX) enzymes into various lipid mediators involved in the regulation of brain immunity. Brain AA metabolism is activated in rodents by the bacterial endotoxin, lipopolysacchari...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9968-1
更新日期:2017-08-01 00:00:00
abstract::The signaling cascades triggered by neurotrophins such as BDNF and by several neurotransmitters and hormones lead to the rapid induction of gene transcription by increasing the intracellular concentration of cAMP and Ca2+. This review examines the mechanisms by which these second messengers control transcriptional ini...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/MN:30:1:091
更新日期:2004-08-01 00:00:00