scholarly journals Culling less fit neurons protects against amyloid-β-induced brain damage and cognitive and motor decline

2018 ◽  
Author(s):  
Dina S. Coelho ◽  
Silvia Schwartz ◽  
Marisa M. Merino ◽  
Barbara Hauert ◽  
Barbara Topfel ◽  
...  
Keyword(s):  
Brain Damage ◽  
Neuronal Death ◽  
Common Knowledge ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Long Term Memory ◽  
Brain Circuits ◽  
Key Aspects

SummaryAlzheimer’s disease (AD) is the most common form of dementia, impairing cognitive and motor functions. One of the pathological hallmarks of AD is neuronal loss, which is not reflected in mouse models of AD. Therefore, the role of neuronal death is still uncertain. Here, we used a Drosophila AD model expressing a secreted form of human amyloid-β42 peptide and show that it recapitulates key aspects of AD pathology, including neuronal death and impaired long-term memory. We found that neuronal apoptosis is mediated by cell fitness-driven neuronal culling, which selectively eliminates impaired neurons from brain circuits. We show that removal of less fit neurons delays amyloid-β42-induced brain damage and protects against cognitive and motor decline, suggesting that - contrary to common knowledge - neuronal death may have a beneficial effect in AD.

The role of PKMζ in the maintenance of long-term memory: a review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamish Patel ◽  
Reza Zamani
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Long Term Potentiation ◽  
Global Memory ◽  
Long Term Memory ◽  
Compensatory Mechanism ◽  
Term Memory ◽  
Kinase C

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

Functional outcome after intracerebral haemorrhage – a review of the potential role of antiapoptotic agents

2016 ◽  
Vol 27 (3) ◽  
pp. 317-327 ◽  
Author(s):  
Abubakar Tijjani Salihu ◽  
Sangu Muthuraju ◽  
Zamzuri Idris ◽  
Abdul Rahman Izaini Ghani ◽  
Jafri Malin Abdullah
Keyword(s):  
Functional Outcome ◽  
Intracerebral Haemorrhage ◽  
Neuronal Death ◽  
Potential Role ◽  
Management Strategies ◽  
Experimental Studies ◽  
Neuronal Loss ◽  
Multimodality Treatment ◽  
Mortality And Morbidity

AbstractIntracerebral haemorrhage (ICH) is the second most common form of stroke and is associated with greater mortality and morbidity compared with ischaemic stroke. The current ICH management strategies, which mainly target primary injury mechanisms, have not been shown to improve patient’s functional outcome. Consequently, multimodality treatment approaches that will focus on both primary and secondary pathophysiology have been suggested. During the last decade, a proliferation of experimental studies has demonstrated the role of apoptosis in secondary neuronal loss at the periphery of the clot after ICH. Subsequently, the value of certain antiapoptotic agents in reducing neuronal death and improving functional outcome following ICH was evaluated in animal models. Preliminary evidence from those studies strongly supports the potential role of antiapoptotic agents in reducing neuronal death and improving functional outcome after intracerebral haemorrhage. Expectedly, the ongoing and subsequent clinical trials will substantiate these findings and provide clear information on the most potent and safe antiapoptotic agents, their appropriate dosage, and temporal window of action, thereby making them suitable for the multimodality treatment approach.

scholarly journals Enhanced Antimycobacterial Response to RecombinantMycobacterium bovis BCG Expressing Latency-Associated Peptide

2001 ◽  
Vol 69 (11) ◽  
pp. 6676-6682 ◽  
Author(s):  
Ben G. Marshall ◽  
Arun Wangoo ◽  
Peadar O'Gaora ◽  
H. Terry Cook ◽  
Rory J. Shaw ◽  
...  
Keyword(s):  
Detrimental Effect ◽  
Transforming Growth Factor ◽  
Initial Response ◽  
Transforming Growth Factor Β ◽  
Mycobacterial Infection ◽  
Acute Stage ◽  
Long Term Memory ◽  
Memory Response

ABSTRACT With a view to exploring the role of transforming growth factor β (TGF-β) during mycobacterial infection, recombinant clones of bacillus Calmette-Guérin (BCG) were engineered to express the natural antagonist of TGF-β, latency-activated peptide (LAP). Induction of TGF-β activity was reduced when macrophages were infected with BCG expressing the LAP construct (LAP-BCG). There was a significant reduction in the growth of LAP-BCG in comparison to that of control BCG following intravenous infection in a mouse model. The enhanced control of mycobacterial replication was associated with an increase in the production of gamma interferon by splenocytes challenged during the acute stage of infection but with a diminished recall response assessed after 13 weeks. Organ weight and hydroxyproline content, representing tissue pathology, were also lower in mice infected with LAP-BCG. The results are consistent with the hypothesis that TGF-β has a detrimental effect on mycobacterial immunity. While a reduction in TGF-β activity augments the initial response to BCG vaccination, early bacterial clearance may adversely affect the induction of a long-term memory response by LAP-BCG.

scholarly journals HYPERMNESIA EUPHORIA OR ANY OTHER DESIRABLE FROM THE POINT OF VIEW OF THE CONSUMER, A PSYCHOTROPIC EFFECT - FIRST AND LEADING ELEMENT IN THE OCCURRENCE AND PRESERVATION OF THE BODY’S DEPENDENCE ON PSYCHOACTIVE FACTORS

2017 ◽  
Vol 9 (3) ◽  
pp. 40-46
Author(s):  
D G Baitubayev ◽  
M D Baitubayeva
Keyword(s):  
Substance Dependence ◽  
Point Of View ◽  
The Body ◽  
Long Term Memory ◽  
Vegetative Nervous System ◽  
Term Memory ◽  
Psychotropic Effect

The work shows the role of the vegetative nervous system (VNS) in the functioning of long-term memory, identity mechanisms of long-term memory in the human evolutionary adaptation and substance dependence. It is shown that, depending on the substance of the body are states like pro- gressive adaptation, that the bodycondition, depending on the chemical and psychogenic psychoactive- factors state of the same circle. It proposed the creation of a branch of medicine that combines study of the dependence of the organism, both on the chemical and psychoactive psychogenic factors. Given the classification of psychoactive factors.Onomastics formulated definitions of terminology changes and additions to be used in a new branch of medicine. Proposed allocation of the International Classifica- tion of diseases separate chapter for the classification of states like progressive adaptation of the body depending on psychoactive factors.

Language processing and language acquisition through the lens of Relational Morphology

2019 ◽  
pp. 201-232
Author(s):  
Ray Jackendoff ◽  
Jenny Audring
Keyword(s):  
Language Acquisition ◽  
Language Processing ◽  
Language Production ◽  
Long Term Memory ◽  
Spreading Activation ◽  
Linguistic Representations ◽  
Memory Network ◽  
Complex Words

This chapter asks what is happening to linguistic representations during language use, and how representations are formed in the course of language acquisition. It is shown how Relational Morphology’s theory of representations can be directly embedded into models of processing and acquisition. Central is that the lexicon, complete with schemas and relational links, constitutes the long-term memory network that supports language production and comprehension. The chapter first discusses processing: the nature of working memory; promiscuous (opportunistic) processing; spreading activation; priming; probabilistic parsing; the balance between storage and computation in recognizing morphologically complex words; and the role of relational links and schemas in word retrieval. It then turns to acquisition, which is to be thought of as adding nodes and relational links to the lexical network. The general approach is based on the Propose but Verify procedure of Trueswell et al. (2013), plus conservative generalization, as in usage-based approaches.

Long-term Memory Upscales Volume of Postsynaptic Densities in the Process that Requires Autophosphorylation of αCaMKII

2019 ◽  
Vol 30 (4) ◽  
pp. 2573-2585 ◽  
Author(s):  
Małgorzata Alicja Śliwińska ◽  
Anna Cały ◽  
Malgorzata Borczyk ◽  
Magdalena Ziółkowska ◽  
Edyta Skonieczna ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Smooth Endoplasmic Reticulum ◽  
Structural Data ◽  
Long Term Memory ◽  
Brain Circuits ◽  
Hippocampal Area ◽  
And Function ◽  
And Storage ◽  
Old Mice

Abstract It is generally accepted that formation and storage of memory relies on alterations of the structure and function of brain circuits. However, the structural data, which show learning-induced and long-lasting remodeling of synapses, are still very sparse. Here, we reconstruct 1927 dendritic spines and their postsynaptic densities (PSDs), representing a postsynaptic part of the glutamatergic synapse, in the hippocampal area CA1 of the mice that underwent spatial training. We observe that in young adult (5 months), mice volume of PSDs, but not the volume of the spines, is increased 26 h after the training. The training-induced growth of PSDs is specific for the dendritic spines that lack smooth endoplasmic reticulum and spine apparatuses, and requires autophosphorylation of αCaMKII. Interestingly, aging alters training-induced ultrastructural remodeling of dendritic spines. In old mice, both the median volumes of dendritic spines and PSDs shift after training toward bigger values. Overall, our data support the hypothesis that formation of memory leaves long-lasting footprint on the ultrastructure of brain circuits; however, the form of circuit remodeling changes with age.

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