Abstract：
:Type 2 diabetes mellitus is a risk factor of Alzheimer's disease (AD), most likely linked to an impairment of insulin signaling in the brain. Liraglutide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analog, facilitates insulin signaling and shows neuroprotective properties. In the present study, we analyzed the effects of liraglutide on the impairment of learning and memory formation induced by amyloid-β protein (Aβ), and the probable underlying electrophysiological and molecular mechanisms. We found that (1) bilateral intrahippocampal injection of Aβ(25-35) resulted in a significant decline of spatial learning and memory of rats in water maze tests, together with a serious depression of in vivo hippocampal late-phase long-term potentiation (L-LTP) in CA1 region of rats; (2) pretreatment with liraglutide effectively and dose-dependently protected against the Aβ(25-35)-induced impairment of spatial memory and deficit of L-LTP; (3) liraglutide injection also activated cAMP signal pathway in the brain, with a nearly doubled increase in the cAMP contents compared with control. These results strongly suggest that upregulation of GLP-1 signaling in the brain, such as application of liraglutide, may be a novel and promising strategy to ameliorate the learning and memory impairment seen in AD.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Han WN,Hölscher C,Yuan L,Yang W,Wang XH,Wu MN,Qi JSdoi
10.1016/j.neurobiolaging.2012.04.009subject
Has Abstractpub_date
2013-02-01 00:00:00pages
576-88issue
2eissn
0197-4580issn
1558-1497pii
S0197-4580(12)00238-2journal_volume
34pub_type
杂志文章abstract：:Striatal dopamine (DA) and metabolite (DOPAC) levels in 8-, 21-, 52- and 104-week-old C57BL mice were compared with those in 11-week-old mice, 20 days after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. DA and DOPAC concentrations expressed relative to striatal wet weight did not change with age. In c...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(91)90087-z
更新日期：1991-09-01 00:00:00
abstract：:We have assessed the frequency of alpha-synuclein (SNCA) mutations in Japanese patients with familial or sporadic Parkinson's disease (PD) and surveyed their associated clinical manifestations. We screened SNCA exon 3 in 988 patients without SNCA multiplications (430 with autosomal dominant PD and 558 with sporadic PD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.05.022
更新日期：2017-09-01 00:00:00
abstract：:In frontotemporal dementia (FTD), the behavioral variant (bv-FTD) and nonfluent variant of primary progressive aphasia (nfv-PPA) reflect a prominent neurodegenerative involvement of the frontal lobe networks, which may include the premotor and motor areas and thus cause heterogeneous clinical symptoms including parkin...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.05.026
更新日期：2018-09-01 00:00:00
abstract：:Aggregates of hyperphosphorylated tau protein are a pathological hallmark of Alzheimer's disease (AD). The origin of AD is multifactorial, and many metabolic disorders originating from overconsumption of fat, cholesterol, and sugar are associated with higher risk of AD later in life. However, the effects of fat, chole...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.07.016
更新日期：2016-11-01 00:00:00
abstract：:The TgCRND8 mouse model of Alzheimer's disease exhibits progressive cortical and hippocampal β-amyloid accumulation, resulting in plaque pathology and spatial memory impairment by 3 months of age. We tested whether TgCRND8 cognitive function is disrupted prior to the appearance of macroscopic plaques in an object reco...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.04.003
更新日期：2012-03-01 00:00:00
abstract：:Middle-aged and aged rats received dorsal hippocampal lesions before performance was evaluated on the radial-arm maze. The maze task contained simultaneous spatial working memory and visually cued reference memory components. Both middle-aged and aged rats that received lesions committed more errors of both types than...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(99)00047-0
更新日期：1999-07-01 00:00:00
abstract：:Psychotic symptoms occur in approximately 40% of subjects with Alzheimer disease (AD with psychosis; AD + P) and identify a subgroup with more rapid cognitive decline. We evaluated in 867 AD subjects the association of AD + P with genes which may modify the pathological process via effects on the accumulation of amylo...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.10.003
更新日期：2011-03-01 00:00:00
abstract：:Detailed analyses of neuronal and astrocyte cell numbers in the ganglion cell layer (GCL) of whole-mounted peripheral retinas from 16 Alzheimer's disease (AD) and 11 control eyes (11 and 9 cases, respectively) demonstrate extensive neuronal loss throughout the entire retina in AD as compared to control eyes. The obser...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(96)00009-7
更新日期：1996-05-01 00:00:00
abstract：:Age-related impairments in episodic memory have been related to a deficiency in semantic processing, based on the finding that elderly adults typically benefit less than young adults from deep, semantic as opposed to shallow, nonsemantic processing of study items. In the present study, we tested the hypothesis that el...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/s0197-4580(03)00032-0
更新日期：2003-11-01 00:00:00
abstract：:Alzheimer's disease (AD) is the most common dementia among the elderly that involves complex neurodegenerative alterations. Multiple cellular processes including regulation of amyloid-β peptide, tau, inflammation, and cell death have been suggested to associate with AD, but it remains largely unknown if long noncoding...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.07.015
更新日期：2015-11-01 00:00:00
abstract：:The loss of presynaptic markers is thought to represent a strong pathologic correlate of cognitive decline in Alzheimer's disease (AD). Spinophilin is a postsynaptic marker mainly located to the heads of dendritic spines. We assessed total numbers of spinophilin-immunoreactive puncta in the CA1 and CA3 fields of hippo...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.03.007
更新日期：2008-09-01 00:00:00
abstract：:In Alzheimer's disease (AD), amyloid-β (Aβ) deposits accumulate in the brain parenchyma and contain fibrils of aggregated heterogeneous Aβ peptides. In addition to fibrils, Aβ aggregates into stable soluble species (termed Aβ oligomers), which are increasingly viewed as the key drivers of early neurodegenerative event...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.05.023
更新日期：2014-11-01 00:00:00
abstract：:Astrocytes play a crucial role in supporting motor neurons in health and disease. However, there have been few attempts to understand how aging may influence this effect. Here, we report that rat astrocytes show an age-dependent senescence phenotype and a significant reduction in their ability to support motor neurons...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.09.020
更新日期：2015-02-01 00:00:00
abstract：:The etiology of Alzheimer's disease is still unknown. Because the disease is specific for human brain, a rational search for early diagnosis or prevention is very difficult. This calls for the development of cellular models that mimick the degeneration of neurons in AD. The brains of AD patients contain markers whose ...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/0197-4580(94)90178-3
更新日期：1994-01-01 00:00:00
abstract：:We measured midbrain structures of 194 subjects without neurological disorders, using T2-weighted MR imaging. Age was negatively correlated with the maximum anteroposterior distance of the midbrain through the substantia nigra (MD), and the average distance from the substantia nigra to the red nucleus (SNRND), while a...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00227-5
更新日期：2001-07-01 00:00:00
abstract：:Transcranial magnetic stimulation may represent an effective means for improving motor function in the elderly. The aim of this study was therefore to investigate the effects of paired associative stimulation (PAS; a plasticity-inducing transcranial magnetic stimulation paradigm) on acquisition of a novel visuomotor t...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.05.017
更新日期：2019-09-01 00:00:00
abstract：:Biochemical, genetic, and epidemiological evidence indicates that inflammation is an essential part of the pathogenesis of Alzheimer's disease. Over the last decade, we and others have focused on the mechanism by which specific inflammatory molecules contribute to the Alzheimer pathogenic pathway. In particular, we ha...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(01)00308-6
更新日期：2001-11-01 00:00:00
abstract：:APOE-ε4 is a major genetic risk factor for late-onset Alzheimer's disease that interacts with other risk factors, but the nature of such combined effects remains poorly understood. We quantified the impact of APOE-ε4, family history (FH) of dementia, and obesity on white matter (WM) microstructure in 165 asymptomatic ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.06.014
更新日期：2020-10-01 00:00:00
abstract：:Mitophagy and mitochondrial biogenesis are 2 pathways that regulate mitochondrial content and metabolism maintaining cellular homeostasis. The imbalance between these opposing processes impairs mitochondrial function and is suggested to be the pathophysiological basis of a variety of neurodegenerative diseases and agi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.03.013
更新日期：2019-07-01 00:00:00
abstract：:Cerebral A(1) adenosine receptors (A(1)AR) fulfill important neuromodulatory and homeostatic functions. The present study examines possible age-related A(1)AR changes in living humans by positron emission tomography (PET) and the A(1)AR ligand [(18)F]CPFPX. Thirty-six healthy volunteers aged 22-74 years were included....
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.08.005
更新日期：2007-12-01 00:00:00
abstract：:Patients with Mild Cognitive Impairment (MCI), exhibiting both working memory and olfactory deficits are likely to progress to Alzheimer's disease (AD). Targeting this pre-clinical AD population with disease modifying agents or cognitive enhancers represents the best strategy for halting or delaying the impact of this...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.11.018
更新日期：2009-09-01 00:00:00
abstract：:In these experiments, potential cognitive deficits in aged rats were studied using an odor-reward association task. Aged Fischer 344 rats first performed to an odor-reward association task. After five daily sessions of 60 trials, the aged rats were globally impaired in comparison to the control rats. However, consider...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)02030-6
更新日期：1996-01-01 00:00:00
abstract：:The significance of amyloid beta protein, especially those ending at the 42nd residue (Abeta42), in the pathogenesis of familial Alzheimer's disease (FAD) linked to the mutations of presenilins, was examined by transfection studies using cultured cells and immunohistochemical analysis of autopsied brains. The levels o...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(98)00027-x
更新日期：1998-01-01 00:00:00
abstract：:We sought to examine the relations between age, gender and brain volumes in an elderly population; we also sought to examine ways of measuring these relations. Three sets of analyses were used: correlational analyses, in which correlations between independent variables and brain volumes were calculated without correct...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.09.016
更新日期：2008-02-01 00:00:00
abstract：:Oxidative stress is considered to be a major contributor to age-related hearing loss (ARHL). Here, we investigated whether pomegranate peel extract (PPE) protected against hearing loss by decreased oxidative stress in the cochlea of D-galactose-induced accelerated aging mice. The aging mice exhibited an increase in he...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.07.007
更新日期：2017-11-01 00:00:00
abstract：:Here we employed human SHEP neuroblastoma cells either stably or inducibly expressing the amyloid precursor protein (APP) intracellular domain (AICD) to investigate its ability to modulate stress-induced cell death. Analysis of effector caspase activation revealed that AICD overexpression was specifically associated w...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.06.012
更新日期：2012-09-01 00:00:00
abstract：:Mural cells (smooth muscle cells and pericytes) regulate blood flow and contribute to vessel stability. We examined whether mural cell changes accompany age-related alterations in the microvasculature of the central nervous system. The retinas of young adult and aged Wistar rats were subjected to immunohistofluorescen...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.10.021
更新日期：2006-12-01 00:00:00
abstract：:The injection of aluminum powder into the cerebrospinal fluid of adult rabbits induced a slowly progressing encephalomyelopathy characterized at first by alteration of posture and then by myoclonic jerks and muscle weakness. Neurofibrillary degeneration was the hallmark of the disease and involved most of the gray are...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(82)90041-0
更新日期：1982-10-01 00:00:00
abstract：:Using resting state (RS) functional magnetic resonance imaging (fMRI), the connectivity patterns of the default mode (DMN), frontoparietal, executive, and salience networks were explored in 13 Alzheimer's disease (AD) patients, 12 amnestic mild cognitive impairment (aMCI) patients, and 13 healthy controls. Compared wi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.06.007
更新日期：2012-08-01 00:00:00
abstract：:Brain deposits of amyloid beta peptide (Abeta) have been a diagnostic hallmark of Alzheimer's disease (AD) for nearly a century. Recent studies have demonstrated that Abeta is also present in peripheral blood. Here, we present evidence that circulating Abeta42 is subject to complement C3b-dependent adherence to comple...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.09.043
更新日期：2006-12-01 00:00:00
