Noradrenergic dysfunction accelerates LPS-elicited inflammation-related ascending sequential neurodegeneration and deficits in non-motor/motor functions

Publication date: Available online 24 June 2019Source: Brain, Behavior, and ImmunityAuthor(s): Sheng Song, Qingshan Wang, Lulu Jiang, Esteban Oyarzabal, Natallia V. Riddick, Belinda Wilson, Sheryl S. Moy, Yen-Yu Ian Shih, Jau-Shyong HongAbstractThe loss of central norepinephrine (NE) released by neurons of the locus coeruleus (LC) occurs with aging, and is thought to be an important factor in producing the many of the nonmotor symptoms and exacerbating the degenerative process in animal models of Parkinson’s disease (PD). We hypothesize that selectively depleting noradrenergic LC neurons prior to the induction of chronic neuroinflammation may not only accelerate the rate of progressive neurodegeneration throughout the brain, but may exacerbate nonmotor and motor behavioral phenotypes that recapitulate symptoms of PD. For this reason, we used a “two-hit” mouse model whereby brain NE were initially depleted by DSP-4 one week prior to exposing mice to LPS. We found that pretreatment with DSP-4 potentiated LPS-induced sequential neurodegeneration in SNpc, hippocampus, and motor cortex, but not in VTA and caudate/putamen. Mechanistic study revealed that DSP-4 enhanced LPS-induced microglial activation and subsequently elevated neuronal oxidative stress in affected brain regions in a time-dependent pattern. To further characterize the effects of DSP-4 on non-motor and motor symptoms in the LPS model, physiological and behavioral tests were performed at different t...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research

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When using drugs or alcohol, you may start to find that you need to keep using more to get high than you did when you first started. When a couple of glasses of wine used to get you plenty drunk, you’re finding that you need a full bottle or even more. This is called building tolerance and can cause some damaging effects to the body, including leading to addiction and death. Using More to Get High: Building Tolerance According to the National Institute on Drug Abuse, tolerance occurs when the person no longer responds to the drug in the way that person initially responded. Stated another way, it takes a higher dose ...
Source: Cliffside Malibu - Category: Addiction Authors: Tags: Addiction Addiction Recovery Alcohol Alcoholism Drug Treatment Substance Abuse alcohol addiction alcohol dependence alcohol dependency alcohol detox alcohol disorder drug addiction drug addiction recovery drug addiction treatment Source Type: blogs
Abstract The loss of central norepinephrine (NE) released by neurons of the locus coeruleus (LC) occurs with aging, and is thought to be an important factor in producing the many of the nonmotor symptoms and exacerbating the degenerative process in animal models of Parkinson's disease (PD). We hypothesize that selectively depleting noradrenergic LC neurons prior to the induction of chronic neuroinflammation may not only accelerate the rate of progressive neurodegeneration throughout the brain, but may exacerbate nonmotor and motor behavioral phenotypes that recapitulate symptoms of PD. For this reason, we used a &...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
As physicians, many of our daily practices involve administration of substances that are shrouded in mystery. Certain medications, specifically opioids, have been part of tragic news stories, and have turned young children into orphans, happy spouses into widows and widowers, and once-aspirational youth into memories. The CDC reports that on average, 130 people die each day from an opioid overdose. With such harrowing statistics, why take opioids in the first place? Well, if used appropriately, opioids can significantly improve pain with relatively tolerable side effects. A short-term course of opioids (typically 3 to 7 da...
Source: Harvard Health Blog - Category: Consumer Health News Authors: Tags: Addiction Pain Management Source Type: blogs
You're reading 5 Surprising Things Stress Can Do to Your Body, originally posted on Pick the Brain | Motivation and Self Improvement. If you're enjoying this, please visit our site for more inspirational articles. You just got off a terrible meeting, your boss gave you an impossible deadline for the next project, your team is pushing you to make extra hours, and you still need to pick up the kids at school. Your body is in a “fight or flight response.” Your stress levels are high, you feel your breath get quicker and even feel your heart beating faster than usual. Although this is all a natural response from y...
Source: PickTheBrain | Motivation and Self Improvement - Category: Consumer Health News Authors: Tags: featured health and fitness self improvement stress Source Type: blogs
AbstractIntroductionSublingual fentanyl tablets (SFTs) have been shown to be a safe and effective option in controlling breakthrough cancer pain (BTcP). However, further examination is required to investigate the use of SFTs among the elderly. The aim of this study was to examine the influence of age in BTcP management with SFTs in the elderly population.MethodsWe performed subgroup analyses of a recently completed trial in two subsets of individuals: patients aged 65 –74 years (low age group) and patients ≥ 75 years (high age group). Pain intensity (PI), onset of pain relief, frequency and...
Source: Drugs in R&D - Category: Drugs & Pharmacology Source Type: research
By just engaging in the basic strategies in the Wheat Belly Total Health, Wheat Belly 10-Day Grain Detox, or Undoctored programs, many mild cases of small intestinal bacterial overgrowth, SIBO, reverse. These efforts thereby restore your ability to ingest prebiotic fibers without diarrhea, bloating, gas, abdominal discomfort, joint pain, and dark emotional feelings. Many people thereby are relieved of irritable bowel syndrome symptoms, fibromyalgia, or restless leg syndrome, or have greater power in reversing autoimmune conditions such as rheumatoid arthritis. Unfortunately, not everybody enjoys reversal of SIBO with our b...
Source: Wheat Belly Blog - Category: Cardiology Authors: Tags: SIBO grain-free probiotic undoctored wheat belly Source Type: blogs
We describe the protocol for a randomized, patient-assessor-blinded, sham controlled trial. Seventy-two eligible patients will be randomly assigned to the intervention group (acupuncture) or the control group (sham acupuncture). All treatment will be given 26 sessions of acupuncture or sham acupuncture over 8 weeks (5 times per week in the first 2 weeks, 3 times per week during weeks 3-6, and 2 times per week during weeks7 and 8). Each treatment will last for 20 minutes. The primary outcome is the change in mean complete spontaneous bowel movements (CSBMs) per week. The secondary outcomes are patient assessment of constipa...
Source: World Journal of Acupuncture Moxibustion - Category: Complementary Medicine Source Type: research
Conclusion: The new field of pediatric PFPT is a safe and effective intervention for children with dyssynergic defecation causing or contributing to chronic constipation, particularly in  children whose comorbidities include anxiety and low ­muscle tone.Dig Dis
Source: Digestive Diseases - Category: Gastroenterology Source Type: research
Abstract Irritable bowel syndrome (IBS) is a functional gastrointestinal syndrome consisting of different bowel pattern subtypes: diarrhea predominant (IBS-D), constipation predominant (IBS-C), and alternating (IBS-A). This paper aimed to identify whether (a) psychological factors implicated in the cognitive behavioral model of IBS were differentially associated with bowel pattern subtypes, (b) whether there were differences in symptom severity and work and social adjustment across the IBS-subtypes. Analysis was conducted on baseline data of 557 individuals with refractory IBS recruited into the Assessing Cognitiv...
Source: Behavior Therapy - Category: Psychiatry & Psychology Authors: Tags: Behav Ther Source Type: research
Albert Sanfeliu1, Karsten Hokamp2, Michael Gill1 and Daniela Tropea1,3*1Neuropsychiatric Genetics, Department of Psychiatry, School of Medicine, Trinity Translational Medicine Institute, St James Hospital, Dublin, Ireland2Department of Genetics, School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland3Department of Psychiatry, School of Medicine, Trinity College Institute for Neuroscience, Trinity College Dublin, Dublin, IrelandRett syndrome is a rare neuropsychiatric disorder with a wide symptomatology including impaired communication and movement, cardio-respiratory abno...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
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