scholarly journals Role for Astroglia-Derived BDNF and MSK1 in Homeostatic Synaptic Plasticity

Neuroglia ◽  
2018 ◽  
Vol 1 (2) ◽  
pp. 381-394 ◽  
Author(s):  
Ulyana Lalo ◽  
Alexander Bogdanov ◽  
Guy W. J. Moss ◽  
Bruno G. Frenguelli ◽  
Yuriy Pankratov

Homeostatic scaling of synaptic strength in response to environmental stimuli may underlie the beneficial effects of an active lifestyle on brain function. Our previous results highlighted a key role for brain-derived neurotrophic factor (BDNF) and mitogen- and stress-activated protein kinase 1 (MSK1) in experience-related homeostatic synaptic plasticity. Astroglia have recently been shown to serve as an important source of BDNF. To elucidate a role for astroglia-derived BDNF, we explored homeostatic synaptic plasticity in transgenic mice with an impairment in the BDNF/MSK1 pathway (MSK1 kinase dead knock-in (KD) mice) and impairment of glial exocytosis (dnSNARE mice). We observed that prolonged tonic activation of astrocytes caused BDNF-dependent upregulation of excitatory synaptic currents accompanied by enlargement of synaptic boutons. We found that exposure to environmental enrichment (EE) and caloric restriction (CR) strongly upregulated excitatory but downregulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on synaptic transmission. In parallel, EE and CR enhanced astrocytic Ca2+-signalling. Importantly, we observed a significant deficit in the effects of EE and CR on synaptic transmission in the MSK1 KD and dnSNARE mice. Combined, our results strongly support the importance of astrocytic exocytosis of BDNF for the beneficial effects of EE and CR on synaptic transmission and plasticity in the ageing brain.

2020 ◽  
Vol 10 (7) ◽  
pp. 462
Author(s):  
Ulyana Lalo ◽  
Alexander Bogdanov ◽  
Guy W. Moss ◽  
Yuriy Pankratov

Experience- and diet-dependent regulation of synaptic plasticity can underlie beneficial effects of active lifestyle on the aging brain. Our previous results demonstrate a key role for brain-derived neurotrophic factor (BDNF) and MSK1 kinase in experience-related homeostatic synaptic scaling. Astroglia has been recently shown to release BDNF via a calcium-dependent mechanism. To elucidate a role for astroglia-derived BDNF in homeostatic synaptic plasticity in the aging brain, we explored the experience- and diet-related alterations of synaptic transmission and plasticity in transgenic mice with impairment of the BDNF/MSK1 pathway (MSK1 kinase dead knock-in mice, MSK1 KD) and impairment of glial exocytosis (dnSNARE mice). We found that prolonged tonic activation of astrocytes caused BDNF-dependent increase in the efficacy of excitatory synapses accompanied by enlargement of synaptic boutons. We also observed that exposure to environmental enrichment (EE) and caloric restriction (CR) enhanced the Ca2+ signalling in cortical astrocytes and strongly up-regulated the excitatory and down-regulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on astroglial and synaptic signalling. The EE- and CR-induced up-scaling of excitatory synaptic transmission in neocortex was accompanied by the enhancement of long-term synaptic potentiation. Importantly, effects of EE and CR on synaptic transmission and plasticity was significantly reduced in the MSK1 KD and dnSNARE mice. Combined, our results suggest that astroglial release of BDNF is important for the homeostatic regulation of cortical synapses and beneficial effects of EE and CR on synaptic transmission and plasticity in aging brain.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Emily Petrus ◽  
Hey-Kyoung Lee

Alzheimer’s disease (AD) is the most common form of age-related dementia, which is thought to result from overproduction and/or reduced clearance of amyloid-beta (Aβ) peptides. Studies over the past few decades suggest that Aβis produced in an activity-dependent manner and has physiological relevance to normal brain functions. Similarly, physiological functions forβ- andγ-secretases, the two key enzymes that produce Aβby sequentially processing the amyloid precursor protein (APP), have been discovered over recent years. In particular, activity-dependent production of Aβhas been suggested to play a role in homeostatic regulation of excitatory synaptic function. There is accumulating evidence that activity-dependent immediate early gene Arc is an activity “sensor,” which acts upstream of Aβproduction and triggers AMPA receptor endocytosis to homeostatically downregulate the strength of excitatory synaptic transmission. We previously reported that Arc is critical for sensory experience-dependent homeostatic reduction of excitatory synaptic transmission in the superficial layers of visual cortex. Here we demonstrate that mice lacking the major neuronalβ-secretase, BACE1, exhibit a similar phenotype: stronger basal excitatory synaptic transmission and failure to adapt to changes in visual experience. Our results indicate that BACE1 plays an essential role in sensory experience-dependent homeostatic synaptic plasticity in the neocortex.


2015 ◽  
Vol 112 (42) ◽  
pp. E5744-E5752 ◽  
Author(s):  
Kristin L. Arendt ◽  
Zhenjie Zhang ◽  
Subhashree Ganesan ◽  
Maik Hintze ◽  
Maggie M. Shin ◽  
...  

Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca2+ levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca2+-levels to RA synthesis remains unknown. Here we identify the Ca2+-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca2+-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity.


2021 ◽  
Vol 15 ◽  
Author(s):  
Henry B. C. Taylor ◽  
Alexander F. Jeans

Homeostatic synaptic plasticity (HSP) regulates synaptic strength both pre- and postsynaptically to ensure stability and efficient information transfer in neural networks. A number of neurological diseases have been associated with deficits in HSP, particularly diseases characterised by episodic network instability such as migraine and epilepsy. Recently, it has become apparent that HSP also plays a role in many neurodegenerative diseases. In this mini review, we present an overview of the evidence linking HSP to each of the major neurodegenerative diseases, finding that HSP changes in each disease appear to belong to one of three broad functional categories: (1) deficits in HSP at degenerating synapses that contribute to pathogenesis or progression; (2) HSP induced in a heterosynaptic or cell non-autonomous manner to support the function of networks of which the degenerating synapses or cells are part; and (3) induction of HSP within the degenerating population of synapses to preserve function and to resist the impact of synapse loss. Understanding the varied manifestations of HSP in neurodegeneration will not only aid understanding mechanisms of disease but could also inspire much-needed novel approaches to therapy.


Author(s):  
Ilma Robo

The treatment of periodontal diseases, mainly of their origin, with the most common clinical manifestation in form of gingival inflammation, is manifold and powerful, including: mechanical therapy, antibiotic, antiseptic and various approaches to treatment, which are recommended to be used within a short period of time. New therapeutic approaches have been proven as alternative treatment to conventional therapy, or in combination with conventional therapies, to reduce the number of periodontopathic pathogens in gingival sulcus. HBOT has a detrimental effect on periodontal microorganisms, as well as beneficial effects on the healing of periodontal tissue, increasing oxygen pressure in gingival pockets. Our study is aimed at reviewing the current published literature on hyperbaric oxygen therapy and focuses on role of HBOT as a therapeutic measure for the individual with periodontal disease in general and for the impact on the recovery of gingival inflammation. HBOT and periodontal treatment together, reduce up to 99% of the gram-negative anaerobic load of subgingival flora. HBOT, significantly reduces subgingival anaerobic flora. Clinical effects in 2-year follow-up of treated patients are sensitive. Reduction of gingival hemorrhage indexes, depth of peritoneum, plaque index, occurs in cases of combination of HBOT and detraction. Reduced load persists up to 2 months after therapy. The significant increase in connective tissue removal starts at the end of 2nd week, to achieve the maximum in week 3-6 of application. HBOT used for re-implantation, stimulates the healing of periodontal membrane, pulp, prevents root resorption, healing of periodontal lining tissues. HBOT, significantly reduces the hemorrhage index with 1.2 value difference, 0.7mm probe depth, reduces gingival fluid by 2. HGH exposure is increased by gingival blood flow, with a difference of 2 in measured value. The therapeutic effects of HBOT in the value of the evaluation index can be saved up to 1-year post treatment.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
C Dupré ◽  
N Barth ◽  
A El Moutawakkil ◽  
F Béland ◽  
F Roche ◽  
...  

Abstract Background Few previous cohorts have studied the different type of physical activities and the degree of cognitive decline. The objective of this work was to analyze the leisure, domestic and professional activities with mild and moderate cognitive disorders in older people living in community. Methods The study used data from the longitudinal and observational study, FrèLE (FRagility: Longitudinal Study of Expressions). The collected data included: socio-demographic variables, lifestyle, and health status (frailty, comorbidities, cognitive status, depression). Cognitive decline was assessed by using: MMSE (Mini-Mental State Examination) and MoCA (Montreal Cognitive Assessment). MoCA was used with two cut-offs (26 and 17) so as to define mild and moderate cognitive disorders Physical activity was assessed by the PASE (Physical Activity Scale for the Elderly), structured in three sections: leisure, domestic and professional activities. Spline and proportional hazards regression models (Cox) were used to estimate the risk of cognitive disorders. Results At baseline, 1623 participants were included and the prevalence of cognitive disorders was 6.9% (MMSE) and 7.2% (MoCA), mild cognitive disorders was 71.3%. The mean age was 77 years, and 52% of the participants were women. After a 2 years long follow-up, we found 6.9% (MMSE) and 6% (MoCA) cognitive disorders on participants. Analyses showed that domestic activities were associated to cognitive decline (HR = 0.52 [0.28-0.94] for MMSE and HR = 0.48 [0.28-0.80] for MoCA). No association were found with leisure and professional activities, and no spline were significant with mild cognitive disorders. Conclusions Analysis showed a relationship between cognitive disorders and type of physical activity, thanks to the use of specific questionnaire of elderly and two global test of cognition. These findings will contribute to the debate on the beneficial effects of physical activity on cognition. Key messages This work allowed to compare two test of cognition and their link with physical activity. It contributes to the debate on the beneficial effects of physical activity on cognition. The work allowed us to see the effect of the different types of physical activity and the impact of the statistical method on the results.


Materials ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1751
Author(s):  
Rosa María Tremiño ◽  
Teresa Real-Herraiz ◽  
Viviana Letelier ◽  
José Marcos Ortega

One of the most popular ways to lessen the impact of the cement industry on the environment consists of substituting clinker by additions. The service life required for real construction elements is generally long, so it would be interesting to obtain information about the effects of new additions after a hardening period of several years. Analyzed here are the effects of the incorporation of volcanic ashes, coming from Calbuco volcano’s last eruption (Chile), as clinker replacement, in the durability and pore structure of mortars, after approximately 4 hardening years (1500 days), in comparison with reference specimens without additions. The substitution percentages of clinker by volcanic powder studied were 10% and 20%. The microstructure was characterized with mercury intrusion porosimetry and impedance spectroscopy. In order to evaluate the pozzolanic activity of the volcanic powder after 1500 days, differential thermal analyses were performed. Water absorption after immersion, steady-state diffusion coefficient and length change were also studied. In accordance with the results obtained, the 10% and 20% substitution of clinker by volcanic powder from the Calbuco volcano showed beneficial effects in the mortars after 4 years, especially regarding the microstructure and chloride diffusion, without noticeable influence in their water absorption.


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