Search results for " Amy"
showing 10 items of 242 documents
The Role of Anabolic Androgenic Steroids in Disruption of the Physiological Function in Discrete Areas of the Central Nervous System
2017
: Anabolic-androgenic steroids (AAS) abuse is often associated with a wide spectrum of adverse effects. These drugs are frequently abused by adolescents and athletes for esthetic purposes, as well as for improvement of their endurance and performances. In this literature review, we evaluated the correlation between AAS and anxiety or aggression. Two pathways are thought to be involved in AAS-induced behavioral disorders. Direct pathway via the amygdalo-fugal pathway, which connects the central nucleus of the amygdala to the brainstem, is involved in cognitive-emotive and homeostatic processes. The latter is modified by chronic AAS use, which subsequently leads to increased anxiety. Indirect…
Comparative Distribution of Relaxin-3 Inputs and Calcium-Binding Protein-Positive Neurons in Rat Amygdala
2016
The neural circuits involved in mediating complex behaviors are being rapidly elucidated using various newly developed and powerful anatomical and molecular techniques, providing insights into the neural basis for anxiety disorders, depression, addiction, and dysfunctional social behaviors. Many of these behaviors and associated physiological processes involve the activation of the amygdala in conjunction with cortical and hippocampal circuits. Ascending subcortical projections provide modulatory inputs to the extended amygdala and its related nodes (or “hubs”) within these key circuits. One such input arises from the nucleus incertus (NI) in the tegmentum, which sends amino acid- and pepti…
Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients
2015
Abstract Background Several studies suggest that pathological changes in Alzheimer’s disease (AD) brain begin around 10–20 years before the onset of cognitive impairment. Biomarkers that can support early diagnosis and predict development of dementia would, therefore, be crucial for patient care and evaluation of drug efficacy. Although cerebrospinal fluid (CSF) levels of Aβ42, tau, and p-tau are well-established diagnostic biomarkers of AD, there is an urgent need to identify additional molecular alterations of neuronal function that can be evaluated at the systemic level. Objectives This study was focused on the analysis of oxidative stress-related modifications of the CSF proteome, from …
Protein misfolding, amyotrophic lateral sclerosis and guanabenz: Protocol for a phase II RCT with futility design (ProMISe trial)
2017
IntroductionRecent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug. A pharmacological action recently discovered is its ability to modulate the synthesis of proteins by the activation of translational factors preventing misfolded protein accumula…
Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation
2017
Alzheimer’s disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalcife…
Acute onset of bulbar amyotrophic lateral sclerosis after flu – look at the differential diagnosis: A case report
2018
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting upper and lower motor neurones. It can be either familial (fALS) or sporadic (sALS). ALS is characterized by muscle weakness and atrophy that can involve the limbs and trunk (i.e. the spinal form of the disease) or speech and swallowing (i.e. the bulbar form). The aetiology of sALS remains unclear although a gene–environment interaction has been proposed as a concomitant trigger for the neurodegenerative process together with viral infections, smoking, heavy metals and pesticide exposure. Herein, we report the case of a 67-year-old woman who experienced an acute onset of bulbar ALS with an atypical clinical cours…
Identification of Phlogacantholide C as a Novel ADAM10 Enhancer from Traditional Chinese Medicinal Plants
2016
Background: Alzheimer’s disease is one of the most prevalent dementias in the elderly population with increasing numbers of patients. One pivotal hallmark of this disorder is the deposition of protein aggregates stemming from neurotoxic amyloid-beta peptides. Synthesis of those peptides has been efficiently prevented in AD model mice by activation of an enzyme called alpha-secretase. Therefore, drugs with the capability to increase the expression of this enzyme, named ADAM10, have been suggested as a valuable therapeutic medication. Methods: We investigated 69 substances from a drug library derived from traditional Chinese medicine by luciferase reporter assay in human neuronal cells for th…
Homer2 and alcohol: A mutual interaction
2017
The past two decades of data derived from addicted individuals and preclinical animal models of addiction implicate a role for the excitatory glutamatergic transmission within the mesolimbic structures in alcoholism. The cellular localization of the glutamatergic receptor subtypes, as well as their signaling efficiency and function, are highly dependent upon discrete functional constituents of the postsynaptic density, including the Homer family of scaffolding proteins. The consequences of repeated alcohol administration on the expression of the Homer family proteins demonstrate a crucial and active role, particularly for the expression of Homer2 isoform, in regulating alcohol-induced behav…
Regulatory effects of simvastatin and apoJ on APP processing and amyloid-beta clearance in blood-brain barrier endothelial cells
2017
Amyloid-β peptides (Aβ) accumulate in cerebral capillaries indicating a central role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer’s disease (AD). Although a relationship between apolipoprotein-, cholesterol- and Aβ metabolism is evident, the interconnecting mechanisms operating in brain capillary endothelial cells (BCEC) are poorly understood. ApoJ (clusterin) is present in HDL that regulates cholesterol metabolism which is disturbed in AD. ApoJ levels are increased in AD brains and in plasma of cerebral amyloid angiopathy (CAA) patients. ApoJ may bind, prevent fibrillization, and enhance clearance of Aβ. We here define a connection of apoJ and cellular cholesterol home…
Pressure effects on α-synuclein amyloid fibrils: An experimental investigation on their dissociation and reversible nature
2017
αâsynuclein amyloid fibrils are found in surviving neurons of Parkinson's disease affected patients, but the role they play in the disease development is still under debate. A growing number of evidences points to soluble oligomers as the major cytotoxic species, while insoluble fibrillar aggregates could even play a protection role. In this work, we investigate αâsynuclein fibrils dissociation induced at high pressure by means of Small Angle X-ray Scattering and Fourier Transform Infrared Spectroscopy. Fibrils were produced from wild type αâsynuclein and two familial mutants, A30P and A53T. Our results enlighten the different reversible nature of αâsynuclein fibrils fragmentati…