Behavioral and Biochemical Implications of Dendrimeric Rivastigmine in Memory-Deficit and Alzheimer's Induced Rodents.

Abstract:

:Exploration of dendrimers for effective drug delivery is giving promising results. The present study was designed and performed to explore the dendrimeric (polyamidoamine-lactoferrin; PAMAM-Lf) formulations for the effective rivastigmine (RIV) delivery against the Alzheimer's induced animal model using lactoferrin as the targeting ligand. RIV delivery through PAMAM-Lf conjugates was highly efficient in the Alzheimer's induced animal model. PAMAM-Lf conjugates also efficiently improved behavioral responses against the chemical memory deficit animal model as well as the Alzheimer's induced animal model, separately. Behavioral responses revealed that motor and spatial memories were significantly improved (p < 0.005) over those from RIV alone. The latency time of PAMAM-Lf-RIV was 1.3 times higher over that of the pure RIV in the rotarod protocol, while it was 2.1-fold reduced in the Morris water maze test. The study also attempted to explore the mechanistic aspect of improved efficacy through biochemical evaluation (AChE histo-enzymology), which reveals that levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were unaffected, but AChE activity was improved for all forms of RIV. Conclusively, PAMAM-Lf conjugates were able to deliver RIV effectively against the Alzheimer's induced animal model. This was further strengthened with the positive results obtained with the behavioral studies of memory-deficit animals and disease-induced animals. The study is among the first studies which report RIV delivery against the Alzheimer's induced animal model using PAMAM dendrimers.

journal_name

ACS Chem Neurosci

authors

Gothwal A,Singh H,Jain SK,Dutta A,Borah A,Gupta U

doi

10.1021/acschemneuro.9b00286

subject

Has Abstract

pub_date

2019-08-21 00:00:00

pages

3789-3795

issue

8

issn

1948-7193

journal_volume

10

pub_type

杂志文章
  • Development of Sulfonamide Photoaffinity Inhibitors for Probing Cellular γ-Secretase.

    abstract::γ-Secretase is a multiprotein complex that catalyzes intramembrane proteolysis associated with Alzheimer's disease and cancer. Here, we have developed potent sulfonamide clickable photoaffinity probes that target γ-secretase in vitro and in cells by incorporating various photoreactive groups and walking the clickable ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00127

    authors: Crump CJ,Murrey HE,Ballard TE,Am Ende CW,Wu X,Gertsik N,Johnson DS,Li YM

    更新日期:2016-08-17 00:00:00

  • ACS chemical neuroscience molecule spotlight on savella.

    abstract::Savella (milnacipran), a selective serotonin and noradrenaline reuptake inhibitor, was approved by the FDA on January 14th, 2009, for the treatment of fibromyalgia. ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/cn1000233

    authors: Hopkins CR

    更新日期:2010-05-19 00:00:00

  • Novel Disassembly Mechanisms of Sigmoid Aβ42 Protofibrils by Introduced Neutral and Charged Drug Molecules.

    abstract::Alzheimer's disease (AD) is characterized by fibrillar deposits of amyloid-β (Aβ) peptides and neurofibrillary tangles of Tau proteins. Aβ peptides are composed of 37-49 residues, among which the Aβ42 isoform is particularly toxic and aggregation-prone and is enriched in the plaques of AD brains and thus considered ce...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00550

    authors: Xing X,Liu C,Ali A,Kang B,Li P,Ai H

    更新日期:2020-01-02 00:00:00

  • Gut Microbiota Dynamics in Parkinsonian Mice.

    abstract::Peripheral immunity is thought to be dysregulated in Parkinson's disease (PD) and may provide an avenue for novel immunotherapeutic interventions. Gut microbiota is a potential factor for modulating immunotherapy response. Considering the possibly complex role of the gut-brain axis in PD, we used a preclinical model t...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00386

    authors: Klann E,Tagliamonte MS,Ukhanova M,Mai V,Vedam-Mai V

    更新日期:2020-10-21 00:00:00

  • Cationic amino acid based lipids as effective nonviral gene delivery vectors for primary cultured neurons.

    abstract::The delivery of specific genes into neurons offers a potent approach for treatment of diseases as well as for the study of neuronal cell biology. Here we investigated the capabilities of cationic amino acid based lipid assemblies to act as nonviral gene delivery vectors in primary cultured neurons. An arginine-based l...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn400036j

    authors: Aoshima Y,Hokama R,Sou K,Sarker SR,Iida K,Nakamura H,Inoue T,Takeoka S

    更新日期:2013-12-18 00:00:00

  • Newly Identified Aplysia SPTR-Gene Family-Derived Peptides: Localization and Function.

    abstract::When individual neurons in a circuit contain multiple neuropeptides, these peptides can target different sets of follower neurons. This endows the circuit with a certain degree of flexibility. Here we identified a novel family of peptides, the Aplysia SPTR-Gene Family-Derived peptides (apSPTR-GF-DPs). We demonstrated ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.7b00513

    authors: Zhang G,Yuan WD,Vilim FS,Romanova EV,Yu K,Yin SY,Le ZW,Xue YY,Chen TT,Chen GK,Chen SA,Cropper EC,Sweedler JV,Weiss KR,Jing J

    更新日期:2018-08-15 00:00:00

  • An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT7 and 5-HT1A Receptor Partial Agonist that Corrects Motor Stereotypy in Mouse Models.

    abstract::Stereotypy (e.g., repetitive hand waving) is a key phenotype of autism spectrum disorder, Fragile X and Rett syndromes, and other neuropsychiatric disorders, and its severity correlates with cognitive and attention deficits. There are no effective treatments, however, for stereotypy. Perturbation of serotonin (5-HT) n...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.5b00099

    authors: Canal CE,Felsing DE,Liu Y,Zhu W,Wood JT,Perry CK,Vemula R,Booth RG

    更新日期:2015-07-15 00:00:00

  • The molecular basis of memory.

    abstract::We propose a tripartite biochemical mechanism for memory. Three physiologic components are involved, namely, the neuron (individual and circuit), the surrounding neural extracellular matrix, and the various trace metals distributed within the matrix. The binding of a metal cation affects a corresponding nanostructure ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn300097b

    authors: Marx G,Gilon C

    更新日期:2012-08-15 00:00:00

  • Alzheimer's Amyloid-β Sequesters Caspase-3 in Vitro via Its C-Terminal Tail.

    abstract::Amyloid-β (Aβ), the main constituent in senile plaques found in the brain of patients with Alzheimer's disease (AD), is considered as a causative factor in AD pathogenesis. The clinical examination of the brains of patients with AD has demonstrated that caspase-3 colocalizes with senile plaques. Cellular studies have ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00049

    authors: Chang YJ,Linh NH,Shih YH,Yu HM,Li MS,Chen YR

    更新日期:2016-08-17 00:00:00

  • Serotonin neuron diversity in the dorsal raphe.

    abstract::The dorsal raphe nucleus contains one of the largest groups of serotonergic neurons in the mammalian brain and is the main site of origin of the serotonergic projection to the cerebral cortex. Early electrophysiological studies suggested that serotonergic neurons in this cell group formed a homogeneous cell class. Mor...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/cn300224n

    authors: Andrade R,Haj-Dahmane S

    更新日期:2013-01-16 00:00:00

  • Analysis of Single Neurons by Perforated Patch Clamp Recordings and MALDI-TOF Mass Spectrometry.

    abstract::Single-cell mass spectrometry has become an established technique to study specific molecular properties such as the neuropeptide complement of identified neurons. Here, we describe a strategy to characterize, by MALDI-TOF mass spectrometry, neurochemical composition of neurons that were identified by their electrophy...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.8b00163

    authors: Neupert S,Fusca D,Kloppenburg P,Predel R

    更新日期:2018-08-15 00:00:00

  • Discovery, Synthesis, and Preclinical Characterization of N-(3-Chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506), a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu4).

    abstract::The efficacy of positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 4 (mGlu4) in preclinical rodent models of Parkinson's disease has been established by a number of groups. Here, we report an advanced preclinically characterized mGlu4 PAM, N-(3-chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00035

    authors: Engers DW,Blobaum AL,Gogliotti RD,Cheung YY,Salovich JM,Garcia-Barrantes PM,Daniels JS,Morrison R,Jones CK,Soars MG,Zhuo X,Hurley J,Macor JE,Bronson JJ,Conn PJ,Lindsley CW,Niswender CM,Hopkins CR

    更新日期:2016-09-21 00:00:00

  • A Novel Negative Allosteric Modulator Selective for GluN2C/2D-Containing NMDA Receptors Inhibits Synaptic Transmission in Hippocampal Interneurons.

    abstract::N-Methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate excitatory synaptic transmission and have been implicated in numerous neurological disorders. NMDARs typically comprise two GluN1 and two GluN2 subunits. The four GluN2 subtypes (GluN2A-GluN2D) have distinct functional properties a...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.7b00329

    authors: Swanger SA,Vance KM,Acker TM,Zimmerman SS,DiRaddo JO,Myers SJ,Bundgaard C,Mosley CA,Summer SL,Menaldino DS,Jensen HS,Liotta DC,Traynelis SF

    更新日期:2018-02-21 00:00:00

  • Real-Time Monitoring of Alzheimer's-Related Amyloid Aggregation via Probe Enhancement-Fluorescence Correlation Spectroscopy.

    abstract::This work describes the use of fluorescence correlation spectroscopy (FCS) and a novel amyloid-binding fluorescent probe, ARCAM 1, to monitor the aggregation of the Alzheimer's disease-associated amyloid β-peptide (Aβ). ARCAM 1 exhibits a large increase in fluorescence emission upon binding to Aβ assemblies, making it...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.5b00176

    authors: Guan Y,Cao KJ,Cantlon A,Elbel K,Theodorakis EA,Walsh DM,Yang J,Shah JV

    更新日期:2015-09-16 00:00:00

  • Luciferins behave like drugs.

    abstract::The light emission chemistry of firefly luciferase can be harnessed to reveal otherwise invisible biological processes occurring in the brains of live animals. Though powerful, the need for the luciferase substrate D-luciferin to traverse the blood-brain barrier poses limitations on the sensitivity and interpretation ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.5b00195

    authors: Mofford DM,Miller SC

    更新日期:2015-08-19 00:00:00

  • Binding of Metal-Ion-Induced Tau Oligomers to Lipid Surfaces Is Enhanced by GSK-3β-Mediated Phosphorylation.

    abstract::While fibrillar deposits of hyperphosphorylated protein tau are a key hallmark of several neurodegenerative diseases such as Alzheimer's disease, small oligomers have been speculated to be the key toxic aggregate species. Trivalent metal ions were shown to promote tau oligomer formation in vitro. However, little is kn...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00459

    authors: Nuebling GS,Plesch E,Ruf VC,Högen T,Lorenzl S,Kamp F,Giese A,Levin J

    更新日期:2020-03-18 00:00:00

  • Facile methodology for monitoring amyloid-β fibrillization.

    abstract::Amyloid-β (Aβ) is a peptide fragment that is prone to aggregate into large fibrils under physiological conditions. Many techniques have been developed to quickly monitor the transition from a primarily monomeric peptide into fibrils. Here we propose a novel method for both incubating and monitoring changes in Aβ aggre...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn300135n

    authors: Cook NP,Martí AA

    更新日期:2012-11-21 00:00:00

  • Functional Characterization of the Prejunctional Receptors Mediating the Inhibition by Ergotamine of the Rat Perivascular Sensory Peptidergic Drive.

    abstract::Calcitonin gene-related peptide (α-CGRP) released from perivascular sensory nerves induces decreases in diastolic blood pressure (DBP). Experimentally, this can be shown by spinal thoracic (T9-T12) electrical stimulation of these afferent fibers. Because ergotamine inhibits these neurogenic vascular responses and disp...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.8b00611

    authors: González-Hernández A,Marichal-Cancino BA,Lozano-Cuenca J,MaassenVanDenBrink A,Villalón CM

    更新日期:2019-07-17 00:00:00

  • A Novel Multifunctional Compound Camellikaempferoside B Decreases Aβ Production, Interferes with Aβ Aggregation, and Prohibits Aβ-Mediated Neurotoxicity and Neuroinflammation.

    abstract::Accumulating evidence suggested that soluble oligomeric β-amyloid protein (Aβ) exerts diverse roles in neuronal cell death, neuroinflammation, oxidative stress, and the eventual dementia associated with Alzheimer's disease (AD). Developing an agent with multiple properties may be a reasonable strategy for the treatmen...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00091

    authors: Yang S,Liu W,Lu S,Tian YZ,Wang WY,Ling TJ,Liu RT

    更新日期:2016-04-20 00:00:00

  • Oligomer Diversity during the Aggregation of the Repeat Region of Tau.

    abstract::The molecular mechanism of protein aggregation is of both fundamental and clinical importance as amyloid aggregates are linked to a number of neurodegenerative disorders. Such protein aggregates include macroscopic insoluble fibrils as well as small soluble oligomeric species. Time-dependent resolution of these specie...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.8b00250

    authors: Kjaergaard M,Dear AJ,Kundel F,Qamar S,Meisl G,Knowles TPJ,Klenerman D

    更新日期:2018-12-19 00:00:00

  • Antidepressive Effect of Arctiin by Attenuating Neuroinflammation via HMGB1/TLR4- and TNF-α/TNFR1-Mediated NF-κB Activation.

    abstract::Inflammation is a potential factor in the pathophysiology of depression. A traditional Chinese herbal medicine, arctiin, and its aglycone, arctigenin, are the major bioactive components in Fructus arctii and exhibit neuroprotective and anti-inflammatory activities. Arctigenin has been reported to have antidepressant-l...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00120

    authors: Xu X,Zeng XY,Cui YX,Li YB,Cheng JH,Zhao XD,Xu GH,Ma J,Piao HN,Jin X,Piao LX

    更新日期:2020-08-05 00:00:00

  • Alzheimer's Disease, the "One-Molecule, One-Target" Paradigm, and the Multitarget Directed Ligand Approach.

    abstract::No selective drugs exist, and we have been designing, synthesizing, and evaluating multitarget-directed ligands since the beginning of modern medicinal chemistry, without knowing it, most possibly. The challenge to discover the efficient Multi-Target Small Molecules (MTSMs) for Alzheimer's disease (AD) therapy implies...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.8b00069

    authors: Oset-Gasque MJ,Marco-Contelles J

    更新日期:2018-03-21 00:00:00

  • Imaging chemical neurotransmission with genetically encoded fluorescent sensors.

    abstract::A major challenge in neuroscience is to decipher the logic of neural circuitry and to link it to learning, memory, and behavior. Synaptic transmission is a critical event underlying information processing within neural circuitry. In the extracellular space, the concentrations and distributions of excitatory, inhibitor...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/cn500280k

    authors: Liang R,Broussard GJ,Tian L

    更新日期:2015-01-21 00:00:00

  • Structure-selective anisotropy assay for amyloid Beta oligomers.

    abstract::Amyloid β (Abeta) peptides in their oligomeric form have been proposed as major toxic species in Alzheimer's disease (AD). There are a limited number of anti-Abeta antibodies specific to oligomeric forms of Abeta compared to the monomeric form, and accurate measurement of oligomeric forms in biological samples, cerebr...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn3001262

    authors: Matveeva EG,Rudolph A,Moll JR,Thompson RB

    更新日期:2012-11-21 00:00:00

  • Discovery of a Tamoxifen-related compound that suppresses glial l-glutamate transport activity without interaction with estrogen receptors.

    abstract::We recently found that tamoxifen suppresses l-glutamate transport activity of cultured astrocytes. Here, in an attempt to separate the l-glutamate transporter-inhibitory activity from the estrogen receptor-mediated genomic effects, we synthesized several compounds structurally related to tamoxifen. Among them, we iden...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn200091w

    authors: Sato K,Kuriwaki J,Takahashi K,Saito Y,Oka J,Otani Y,Sha Y,Nakazawa K,Sekino Y,Ohwada T

    更新日期:2012-02-15 00:00:00

  • Involvement of protein kinase C in morphine tolerance at spinal levels of rats.

    abstract::The present study was performed to investigate the possible role of protein kinase C (PKC) in morphine tolerance at spinal levels of rats. Intrathecal injection of 10 μg of morphine induced increases in the hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation in rats. After intrathecal inject...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn900005d

    authors: Jin WY,Yu LC

    更新日期:2010-02-17 00:00:00

  • Pharmacological Characterizations of anti-Dementia Memantine Nitrate via Neuroprotection and Vasodilation in Vitro and in Vivo.

    abstract::We have previously designed and synthesized a series of novel memantine nitrates, and some of them have shown neuroprotective effects; however, the detailed mechanisms remain unknown. In this study, we demonstrated that MN-12, one of the memantine nitrates, concentration-dependently protected against glutamate-induced...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00242

    authors: Mak S,Liu Z,Wu L,Guo B,Luo F,Liu Z,Hu S,Wang J,Cui G,Sun Y,Wang Y,Zhang G,Han Y,Zhang Z

    更新日期:2020-02-05 00:00:00

  • Unraveling the Role of Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Myasthenia Gravis.

    abstract::Myasthenia gravis (MG) is an autoimmune T cell-dependent B cell-mediated disorder of the neuromuscular junction (NMJ) characterized by fluctuating skeletal muscle weakness, most commonly attributed to pathogenic autoantibodies against postsynaptic nicotinic acetylcholine receptors (AChRs). Although MG pathogenesis is ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00678

    authors: Angelopoulou E,Paudel YN,Piperi C

    更新日期:2020-03-04 00:00:00

  • Detection of orexin A neuropeptide in biological fluids using a zinc oxide field effect transistor.

    abstract::Biomarkers which are indicative of acute physiological and emotional states are studied in a number of different areas in cognitive neuroscience. Currently, many cognitive studies are conducted based on programmed tasks followed by timed biofluid sampling, central laboratory processing, and followed by data analysis. ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn300159e

    authors: Hagen J,Lyon W,Chushak Y,Tomczak M,Naik R,Stone M,Kelley-Loughnane N

    更新日期:2013-03-20 00:00:00

  • Predicting Multi-Interfacial Binding Mechanisms of NLRP3 and ASC Pyrin Domains in Inflammasome Activation.

    abstract::NLRP3-PYD inflammasome activates an inflammatory pathway in response to a wide variety of cell damage or infections. Dysregulated NLRP3 inflammatory signaling has many chronic inflammatory and autoimmune disorders. NLRP3 and ASC have a PYD, a superfamily member of the Death Domain, which plays a key role in inflammato...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00519

    authors: Riaz M,Rehman AU,Shah SA,Rafiq H,Lu S,Qiu Y,Wadood A

    更新日期:2021-01-27 00:00:00