scholarly journals Plasticity in visual cortex is disrupted in a mouse model of tauopathy and neurodegeneration

Author(s):  
Amalia Papanikolaou ◽  
Fabio Rodrigues ◽  
Joanna Holeniewska ◽  
Keith Phillips ◽  
Aman Saleem ◽  
...  

Abstract Neurodegeneration is a hallmark of many dementias and thought to underlie a progressive impairment of neural plasticity. Previous work in mouse models of neurodegeneration shows pronounced changes in artificially-induced plasticity in hippocampus, perirhinal and prefrontal cortex. However, it is not known how neurodegeneration disrupts intrinsic forms of brain plasticity. Here we characterised the impact of tau-driven neurodegeneration on a simple form of intrinsic plasticity in the visual system, which allowed us to track plasticity at both long (days) and short (minutes) timescales. We studied rTg4510 transgenic mice at early stages of neurodegeneration (5 months) and a more advanced stage (8 months). We recorded local field potentials in the primary visual cortex while animals were repeatedly exposed to a stimulus over 9 days. We found that both short- and long-term visual plasticity were already disrupted at early stages of neurodegeneration, and further reduced in older animals, such that it was abolished in mice expressing mutant tau. Additionally, visually evoked behaviours were disrupted in both younger and older mice expressing mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy.

2020 ◽  
Author(s):  
Steven F. Grieco ◽  
Xin Qiao ◽  
Xiaoting Zheng ◽  
Yongjun Liu ◽  
Lujia Chen ◽  
...  

SummarySubanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine’s effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces down-regulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.Highlights○ Disinhibition of excitatory cells by ketamine occurs in a fast and sustained manner○ Ketamine evokes NRG1 downregulation and excitatory input loss to PV cells○ Ketamine induced plasticity is blocked by exogenous NRG1 or its receptor knockout○ PV inhibitory cells are the initial functional locus underlying ketamine’s effects


2020 ◽  
Author(s):  
Amalia Papanikolaou ◽  
Fabio R. Rodrigues ◽  
Joanna Holeniewska ◽  
Keith Phillips ◽  
Aman B. Saleem ◽  
...  

Neurodegeneration is a hallmark of many dementias and is thought to underlie a progressive impairment of neural plasticity. How neurodegeneration affects plasticity in neural circuits is not known. We therefore characterised the impact of tau-driven neurodegeneration on plasticity in the visual system, where normal function is well understood. We studied a very simple form of visual plasticity that allowed us to track both long timescales (across days) and shorter timescales (over minutes). We recorded the local field potential in the primary visual cortex of rTg4510 transgenic mice, a mouse model of tauopathy, while animals were repeatedly exposed to the same stimulus over the course of 9 days. We studied animals at early stages of neurodegeneration (5 months old) and at a more advanced stage where pathology is evident (8 months). We found that both short- and long-term visual plasticity were already disrupted at early stages of neurodegeneration, and were further reduced in older animals, such that it was abolished in mice expressing the mutant tau. Additionally, we found that visually evoked behaviours were disrupted in both younger and older mice expressing the mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy, even at early stages of neurodegeneration. This simple measure of neural plasticity may help understand how neurodegeneration disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease.HighlightsVisual plasticity is disrupted at early stages of neurodegeneration in rTg4510 miceVisual plasticity is reduced in older animals, particularly during neurodegenerationInstinctive visual behaviours are reduced in neurodegenerationShort-term visual plasticity is reduced in neurodegeneration


2016 ◽  
Vol 224 (2) ◽  
pp. 102-111 ◽  
Author(s):  
Carsten M. Klingner ◽  
Stefan Brodoehl ◽  
Gerd F. Volk ◽  
Orlando Guntinas-Lichius ◽  
Otto W. Witte

Abstract. This paper reviews adaptive and maladaptive mechanisms of cortical plasticity in patients suffering from peripheral facial palsy. As the peripheral facial nerve is a pure motor nerve, a facial nerve lesion is causing an exclusive deefferentation without deafferentation. We focus on the question of how the investigation of pure deefferentation adds to our current understanding of brain plasticity which derives from studies on learning and studies on brain lesions. The importance of efference and afference as drivers for cortical plasticity is discussed in addition to the crossmodal influence of different competitive sensory inputs. We make the attempt to integrate the experimental findings of the effects of pure deefferentation within the theoretical framework of cortical responses and predictive coding. We show that the available experimental data can be explained within this theoretical framework which also clarifies the necessity for maladaptive plasticity. Finally, we propose rehabilitation approaches for directing cortical reorganization in the appropriate direction and highlight some challenging questions that are yet unexplored in the field.


2018 ◽  
pp. 70-84
Author(s):  
Ph. S. Kartaev ◽  
Yu. I. Yakimova

The paper studies the impact of the transition to the inflation targeting regime on the magnitude of the pass-through effect of the exchange rate to prices. We analyze cross-country panel data on developed and developing countries. It is shown that the transition to this regime of monetary policy contributes to a significant reduction in both the short- and long-term pass-through effects. This decline is stronger in developing countries. We identify the main channels that ensure the influence of the monetary policy regime on the pass-through effect, and examine their performance. In addition, we analyze the data of time series for Russia. It was concluded that even there the transition to inflation targeting led to a decrease in the dependence of the level of inflation on fluctuations in the ruble exchange rate.


2016 ◽  
Author(s):  
Terri S. Hogue ◽  
◽  
Samuel Saxe ◽  
Ryan Logan ◽  
Kyle Knipper ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 1019
Author(s):  
Barbara Frączek ◽  
Aleksandra Pięta ◽  
Adrian Burda ◽  
Paulina Mazur-Kurach ◽  
Florentyna Tyrała

The aim of this meta-analysis was to review the impact of a Paleolithic diet (PD) on selected health indicators (body composition, lipid profile, blood pressure, and carbohydrate metabolism) in the short and long term of nutrition intervention in healthy and unhealthy adults. A systematic review of randomized controlled trials of 21 full-text original human studies was conducted. Both the PD and a variety of healthy diets (control diets (CDs)) caused reduction in anthropometric parameters, both in the short and long term. For many indicators, such as weight (body mass (BM)), body mass index (BMI), and waist circumference (WC), impact was stronger and especially found in the short term. All diets caused a decrease in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), albeit the impact of PD was stronger. Among long-term studies, only PD cased a decline in TC and LDL-C. Impact on blood pressure was observed mainly in the short term. PD caused a decrease in fasting plasma (fP) glucose, fP insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) and glycated hemoglobin (HbA1c) in the short run, contrary to CD. In the long term, only PD caused a decrease in fP glucose and fP insulin. Lower positive impact of PD on performance was observed in the group without exercise. Positive effects of the PD on health and the lack of experiments among professional athletes require longer-term interventions to determine the effect of the Paleo diet on athletic performance.


2021 ◽  
Vol 11 (6) ◽  
pp. 483
Author(s):  
Marwa Saadaoui ◽  
Manoj Kumar ◽  
Souhaila Al Khodor

The COVID-19 pandemic is a worldwide, critical public health challenge and is considered one of the most communicable diseases that the world had faced so far. Response and symptoms associated with COVID-19 vary between the different cases recorded, but it is amply described that symptoms become more aggressive in subjects with a weaker immune system. This includes older subjects, patients with chronic diseases, patients with immunosuppression treatment, and pregnant women. Pregnant women are receiving more attention not only because of their altered physiological and immunological function but also for the potential risk of viral vertical transmission to the fetus or infant. However, very limited data about the impact of maternal infection during pregnancy, such as the possibility of vertical transmission in utero, during birth, or via breastfeeding, is available. Moreover, the impact of infection on the newborn in the short and long term remains poorly understood. Therefore, it is vital to collect and analyze data from pregnant women infected with COVID-19 to understand the viral pathophysiology during pregnancy and its effects on the offspring. In this article, we review the current knowledge about pre-and post-natal COVID-19 infection, and we discuss whether vertical transmission takes place in pregnant women infected with the virus and what are the current recommendations that pregnant women should follow in order to be protected from the virus.


Author(s):  
Lise D. Cloedt ◽  
Kenza Benbouzid ◽  
Annie Lavoie ◽  
Marie-Élaine Metras ◽  
Marie-Christine Lavoie ◽  
...  

AbstractDelirium is associated with significant negative outcomes, yet it remains underdiagnosed in children. We describe the impact of implementing a pain, agitation, and delirium (PAD) bundle on the rate of delirium detection in a pediatric intensive care unit (PICU). This represents a single-center, pre-/post-intervention retrospective and prospective cohort study. The study was conducted at a PICU in a quaternary university-affiliated pediatric hospital. All patients consecutively admitted to the PICU in October and November 2017 and 2018. Purpose of the study was describe the impact of the implementation of a PAD bundle. The rate of delirium detection and the utilization of sedative and analgesics in the pre- and post-implementation phases were measured. A total of 176 and 138 patients were admitted during the pre- and post-implementation phases, respectively. Of them, 7 (4%) and 44 (31.9%) were diagnosed with delirium (p < 0.001). Delirium was diagnosed in the first 48 hours of PICU admission and lasted for a median of 2 days (interquartile range [IQR]: 2–4). Delirium diagnosis was higher in patients receiving invasive ventilation (p < 0.001). Compliance with the PAD bundle scoring was 79% for the delirium scale. Score results were discussed during medical rounds for 68% of the patients in the post-implementation period. The number of patients who received opioids and benzodiazepines and the cumulative doses were not statistically different between the two cohorts. More patients received dexmedetomidine and the cumulative daily dose was higher in the post-implementation period (p < 0.001). The implementation of a PAD bundle in a PICU was associated with an increased recognition of delirium diagnosis. Further studies are needed to evaluate the impact of this increased diagnostic rate on short- and long-term outcomes.


2021 ◽  
Vol 4 (7) ◽  
pp. 4-19
Author(s):  
Akmal Baltayevich Allakuliev ◽  

The article examines the interaction of the country's GDP with the state budget in the short and long term, the impact of the macro-fiscal mechanism on the country's economic growth on the example of Uzbekistan.The aim of the study is to identify dynamic correlations between the country's state budget expenditures and the economic growth of the macro-fiscal mechanism in the short and long term, as well as to analyze the approximation or rate of return of GDP and the state budget to equilibrium during various macroeconomic shocks. and hesitation.The scientific novelties of the research are:


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