Reducing hippocampal extracellular matrix reverses early memory deficits in a mouse model of Alzheimer’s disease

Végh, Marlene J.; Heldring, Céline M; Kamphuis, Willem; Hijazi, Sara; Timmerman, A. J.; Li, Ka Wan; Nierop, Pim van; Mansvelder, Huibert D.; Hol, Elly M.; Smit, August B.; Kesteren, Ronald E. van

doi:10.1186/s40478-014-0076-z

Cited by 96 publications

(112 citation statements)

References 67 publications

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“…These increases in expression occurred with impairment of long-term potentiation and contextual memory, before the onset of plaque formation. Interestingly, chondroitinase ABC injection into the hippocampus restored both long-term potentiation and contextual memory performance [133]. Another recent study used laser capture microdissection (LCM) to excise hippocampal subareas CA1 and subiculum of 40 AD brains with subsequent LC-MS/MS-based proteomics.…”

Section: Changes In Brain Ecm In Neurodegenerative Conditionsmentioning

confidence: 99%

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Sethi

Zaia

2016

Anal Bioanal Chem

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Brain extracellular matrix (ECM) is a highly organized system that consists of collagens, non-collagenous proteins, glycoproteins, hyaluronan and proteoglycans (PGs). Recognized physiological roles of ECM include developmental regulation, tissue homeostasis, cell migration, proliferation, differentiation, neuronal plasticity, and neurite outgrowth. Aberrant ECM structure is associated with brain neurodegenerative conditions. This review focuses on two neurodegenerative conditions, schizophrenia (Sz) and Alzheimer's disease (AD), and summarizes recent findings of altered ECM components, including PGs, glycosaminoglycans (GAGs), proteins and glycoproteins, and proteins and genes related to other brain components. The scope includes immunohistochemical, genomics, transcriptomics, proteomics and glycomics studies, and a critical assessment of current state of proteomics studies for neurodegenerative disorders. The intent is to summarize the ECM molecular alterations associated with neurodegenerative pathophysiology.

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Section: Changes In Brain Ecm In Neurodegenerative Conditionsmentioning

confidence: 99%

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Sethi

Zaia

2016

Anal Bioanal Chem

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“…ADAMTS family members may be utilized to develop therapies for neurodegenerative and neurological disorders. Recently, Veǵh and collaborators [84] reported that increased ECM proteins, including brevican, hyaluronan and proteoglycan link protein 1, neurocan and tenascin-R, were found at an early age in Alzheimer model mice associated with a loss of contextual fear memory and long-term potentiation (LTP) defect. The behavioral plasticity (fear conditioning) and physiological plasticity (LTP) are early affected in APP/PS1 mice and that treatment with chondroitinase ABC reverses these early deficits.…”

Section: The Possible Functions Of Adamts Proteases In Admentioning

confidence: 99%

Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease

Gürses¹,

Ural²,

Güleç³

et al. 2016

Aging and disease

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The extracellular matrix (ECM) is an environment that has various enzymes attended in regeneration and restoration processes which is very important to sustain physiological and biological functions of central nervous system (CNS). One of the participating enzyme systems in ECM turnover is matrix metalloproteinases. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS) is a unique family of ECM proteases found in mammals.Components of this family may be distinguished from the ADAM (A Disintegrin and Metalloproteinase) family based on the multiple copies of thrombospondin 1-like repeats. The considerable role of the ADAMTS in the CNS continues to develop. Evidences indicate that ADAMTS play an important role in neuroplasticity as well as nervous system pathologies such as Alzheimer's disease (AD). It is hopeful and possible that ADAMTS family members may be utilized to develop therapies for CNS pathologies, ischemic injuries, neurodegenerative and neurological diseases. To understand and provide definitive data on ADAMTS to improve structural and functional recovery in CNS injury and diseases, this review aimed to enlighten the subject extensively to reach certain information on metalloproteinases and related molecules/enzymes. It will be interesting to examine how ADAMTS expression and action would affect the initiation/progression of above-mentioned clinical situations, especially AD.

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“…Genetic alterations or environmental stimuli that affect the composition of the ECM are thought to contribute to neurodegenerative and psychiatric disorders, including drug addiction (Lubbers et al, 2014a;Vegh et al, 2014). The ECM consists mainly of deposits of hyaluronic acid, glycoproteins and proteoglycans in the extracellular space (Dityatev and Schachner, 2003).…”

Section: Introductionmentioning

confidence: 99%

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference

Lubbers

Matos

Horn

et al. 2015

Neuropsychopharmacol

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Cocaine-associated environmental cues sustain relapse vulnerability by reactivating long-lasting memories of cocaine reward. During periods of abstinence, responding to cocaine cues can time-dependently intensify a phenomenon referred to as 'incubation of cocaine craving'. Here, we investigated the role of the extracellular matrix protein brevican in recent (1 day after training) and remote (3 weeks after training) expression of cocaine conditioned place preference (CPP). Wild-type and Brevican heterozygous knock-out mice, which express brevican at~50% of wild-type levels, received three cocaine-context pairings using a relatively low dose of cocaine (5 mg/kg). In a drug-free CPP test, heterozygous mice showed enhanced preference for the cocaine-associated context at the remote time point compared with the recent time point. This progressive increase was not observed in wild-type mice and it did not generalize to contextualfear memory. Virally mediated overexpression of brevican levels in the hippocampus, but not medial prefrontal cortex, of heterozygous mice prevented the progressive increase in cocaine CPP, but only when overexpression was induced before conditioning. Postconditioning overexpression of brevican did not affect remote cocaine CPP, suggesting that brevican limited the increase in remote CPP by altering neuro-adaptive mechanisms during cocaine conditioning. We provide causal evidence that hippocampal brevican levels control time-dependent enhancement of cocaine CPP during abstinence, pointing to a novel substrate that regulates incubation of responding to cocaine-associated cues.

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Reducing hippocampal extracellular matrix reverses early memory deficits in a mouse model of Alzheimer’s disease

Cited by 96 publications

References 67 publications

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference

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