scholarly journals Optimization and validation of online column-switching assisted HPLC-spectrometric method for quantification of dansylated endocannabinoids and neurotransmitters in animal models of brain diseases

2019 ◽  
Vol 3 (1) ◽  
pp. 083-093
Author(s):  
Baranyi Maria ◽  
Sperlagh Beata
2019 ◽  
Vol 2 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Pike-See Cheah ◽  
John O. Mason ◽  
King Hwa Ling

The human brain is made up of billions of neurons and glial cells which are interconnected and organized into specific patterns of neural circuitry, and hence is arguably the most sophisticated organ in human, both structurally and functionally. Studying the underlying mechanisms responsible for neurological or neurodegenerative disorders and the developmental basis of complex brain diseases such as autism, schizophrenia, bipolar disorder, Alzheimer’s and Parkinson’s disease has proven challenging due to practical and ethical limitations on experiments with human material and the limitations of existing biological/animal models. Recently, cerebral organoids have been proposed as a promising and revolutionary model for understanding complex brain disorders and preclinical drug screening.


2021 ◽  
Vol 22 (19) ◽  
pp. 10236
Author(s):  
Yukihiro Ohno ◽  
Naofumi Kunisawa ◽  
Saki Shimizu

Inwardly rectifying Kir4.1 channels in astrocytes mediate spatial potassium (K+) buffering, a clearance mechanism for excessive extracellular K+, in tripartite synapses. In addition to K+ homeostasis, astrocytic Kir4.1 channels also play an essential role in regulating extracellular glutamate levels via coupling with glutamate transporters. Moreover, Kir4.1 channels act as novel modulators of the expression of brain-derived neurotrophic factor (BDNF) in astrocytes. Specifically, inhibition of astrocytic Kir4.1 channels elevates extracellular K+ and glutamate levels at synapses and facilitates BDNF expression in astrocytes. These changes elevate neural excitability, which may facilitate synaptic plasticity and connectivity. In this article, we summarize the functions and pharmacological features of Kir4.1 channels in astrocytes and highlight the importance of these channels in the treatment of brain diseases. Although further validation in animal models and human patients is required, astrocytic Kir4.1 channel could potentially serve as a novel therapeutic target for the treatment of depressive disorders and epilepsy.


Author(s):  
Nadja Van Camp ◽  
Sonia Lavisse ◽  
Pauline Roost ◽  
Francesco Gubinelli ◽  
Ansel Hillmer ◽  
...  

AbstractOver the last 30 years, the 18-kDa TSPO protein has been considered as the PET imaging biomarker of reference to measure increased neuroinflammation. Generally assumed to image activated microglia, TSPO has also been detected in endothelial cells and activated astrocytes. Here, we provide an exhaustive overview of the recent literature on the TSPO-PET imaging (i) in the search and development of new TSPO tracers and (ii) in the understanding of acute and chronic neuroinflammation in animal models of neurological disorders. Generally, studies testing new TSPO radiotracers against the prototypic [11C]-R-PK11195 or more recent competitors use models of acute focal neuroinflammation (e.g. stroke or lipopolysaccharide injection). These studies have led to the development of over 60 new tracers during the last 15 years. These studies highlighted that interpretation of TSPO-PET is easier in acute models of focal lesions, whereas in chronic models with lower or diffuse microglial activation, such as models of Alzheimer’s disease or Parkinson’s disease, TSPO quantification for detection of neuroinflammation is more challenging, mirroring what is observed in clinic. Moreover, technical limitations of preclinical scanners provide a drawback when studying modest neuroinflammation in small brains (e.g. in mice). Overall, this review underlines the value of TSPO imaging to study the time course or response to treatment of neuroinflammation in acute or chronic models of diseases. As such, TSPO remains the gold standard biomarker reference for neuroinflammation, waiting for new radioligands for other, more specific targets for neuroinflammatory processes and/or immune cells to emerge.


2013 ◽  
Vol 15 (3) ◽  
pp. 263-278 ◽  

A plethora of magnetic resonance (MR) techniques developed in the last two decades provide unique and noninvasive measurement capabilities for studies of basic brain function and brain diseases in humans. Animal model experiments have been an indispensible part of this development. MR imaging and spectroscopy measurements have been employed in animal models, either by themselves or in combination with complementary and often invasive techniques, to enlighten us about the information content of such MR methods and/or verify observations made in the human brain. They have also been employed, with or independently of human efforts, to examine mechanisms underlying pathological developments in the brain, exploiting the wealth of animal models available for such studies. In this endeavor, the desire to push for ever-higher spatial and/or spectral resolution, better signal-to-noise ratio, and unique image contrast has inevitably led to the introduction of increasingly higher magnetic fields. As a result, today, animal model studies are starting to be conducted at magnetic fields ranging from ~ 11 to 17 Tesla, significantly enhancing the armamentarium of tools available for the probing brain function and brain pathologies.


2019 ◽  
Vol 42 ◽  
Author(s):  
Nicole M. Baran

AbstractReductionist thinking in neuroscience is manifest in the widespread use of animal models of neuropsychiatric disorders. Broader investigations of diverse behaviors in non-model organisms and longer-term study of the mechanisms of plasticity will yield fundamental insights into the neurobiological, developmental, genetic, and environmental factors contributing to the “massively multifactorial system networks” which go awry in mental disorders.


2015 ◽  
Vol 223 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Georg Juckel

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.


2020 ◽  
Vol 134 (3) ◽  
pp. 248-266
Author(s):  
Javed Iqbal ◽  
Frank Adu-Nti ◽  
Xuejiao Wang ◽  
Hui Qiao ◽  
Xin-Ming Ma
Keyword(s):  

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