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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

How early-life events "set the stage" for adult disease has emerged as a research focus. Historically, the epidemiology of disease risk factors has centered on adult life, with little scrutiny of early-life events. Here we review the concept that events in early life may contribute to late-life neurodegenerative disease development, with a focus on Parkinson disease (PD) and Alzheimer disease (AD). Suspect events in early life include infections, stress, poor nutrition, and environmental factors such as chemical and pesticide exposure. Adiposity appears to contribute to both PD and AD; and because early-life events contribute to the development of obesity, linkages may exist between early determinants of obesity and the subsequent development of these neurologic diseases. Many now suggest a life-course approach for determining the relative contributions of genetic and environmental factors in any chronic disease. This requires determining when during the life course that a given exposure has its greatest effect and how exposures may accumulate over the life span. The data for PD and AD suggest that a number of insults occurring early in life may lead or contribute to these diseases. More definitive knowledge of the key risk factors involved will be needed to implement intervention and preventative strategies early in life to dampen or prevent any adverse late-life outcomes.
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PMID:Do early-life insults contribute to the late-life development of Parkinson and Alzheimer diseases? 1880 66

Implantation of deep brain stimulation (DBS) electrodes via stereotactic neurosurgery has become a standard procedure for the treatment of Parkinson's disease. More recently, the range of neuropsychiatric conditions and the possible target structures suitable for DBS have greatly increased. The former include obsessive compulsive disease, depression, obesity, tremor, dystonia, Tourette's syndrome and cluster-headache. In this article we argue that several of the target structures for DBS (nucleus accumbens, posterior inferior hypothalamus, nucleus subthalamicus, nuclei in the thalamus, globus pallidus internus, nucleus pedunculopontinus) are located at strategic positions within brain circuits related to motivational behaviors, learning, and motor regulation. Recording from DBS electrodes either during the operation or post-operatively from externalized leads while the patient is performing cognitive tasks tapping the functions of the respective circuits provides a new window on the brain mechanisms underlying these functions. This is exemplified by a study of a patient suffering from obsessive-compulsive disease from whom we recorded in a flanker task designed to assess action monitoring processes while he received a DBS electrode in the right nucleus accumbens. Clear error-related modulations were obtained from the target structure, demonstrating a role of the nucleus accumbens in action monitoring. Based on recent conceptualizations of several different functional loops and on neuroimaging results we suggest further lines of research using this new window on brain functions.
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PMID:Contribution of subcortical structures to cognition assessed with invasive electrophysiology in humans. 1898 9

Due, in large part, to the significant advances in PC hardware that have been made over the last 3 years, PC-based virtual environments are approaching reality. Virtual Reality Environments for Psychoneurophysiological Assessment and Rehabilitation (VREPAR) are two European Community funded projects (Telematics for health-HC 1053/HC 1055, http:// www.psicologia.net) that are trying to develop a PC-based virtual reality system (PC-VRS) for the medical market that can be marketed at a price that is accessible to its possible endusers (hospitals, universities, and research centres) and that would have the modular, connectability, and interoperability characteristics that the existing systems lack. In particular, the projects are developing three hardware/software modules for the application of the PCVRS in psycho-neuro-physiological assessment and rehabilitation. The chosen development areas are eating disorders (bulimia, anorexia, and obesity), movement disorders (Parkinson's disease and torsion dystonia) and stroke disorders (unilateral neglect and hemiparesis). This article describes the rationale of the modules and the preliminary results obtained.
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PMID:VREPAR projects: the use of virtual environments in psycho-neuro-physiological assessment and rehabilitation. 1917 65

Virtual Reality Environments for Psychoneurophysiological Assessment and Rehabilitation (VREPAR) are two European Community funded projects (Telematics for health-HC 1053/HC 1055-http://www.psicologia.net) whose aim is (a) to develop a PC based virtual reality system (PC-VRS) for the medical market that can be marketed at a price that is accessible to its possible endusers (hospitals, universities, and research centres) and that would have the modular, connectability and interoperability characteristics that the existing systems lack; and (b) to develop three hardware/software modules for the application of the PC-VRS in psychoneurophysiological assessment and rehabilitation. The chosen development areas are eating disorders (bulimia, anorexia, and obesity), movement disorders (Parkinson's disease and torsion dystonia), and stroke disorders (unilateral neglect and hemiparesis). In particular, the VREPAR 2 project is now testing the eating disorders module on a clinical sample.
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PMID:VREPAR 2: VR in eating disorders. 1917 66

The various components of the endocannabinoid system were discovered in the last twenty years. The cannabinoid system has attracted pharmacologists interest for its potential as therapeutic targets for several diseases ranging from obesity to Parkinson's disease and from multiple sclerosis to pain. Research initially focused on cannabinoid receptor 1 (CB1), but, due to psychotropic side effects related to its activation, the attempts to develop an agonist drug for this receptor has been so far unsuccessful. Recently the possibility to target CB2 has emerged as an alternative for the treatment of pain. The main advantage of targeting CB2 resides in the possibility to elicit the analgesic effect without the psychotropic side effects. Evidence of the analgesic effect of CB2 selective agonists has been obtained in various models of both inflammatory and neuropathic chronic pain. To explain the mechanism at the basis of this analgesic effect different hypotheses have been proposed: effect on inflammatory cells, reduction of basal NGF tone, induction of beta-endorphin release from keratinocytes, direct action on nociceptors. Evidence in support of this last hypothesis comes from down regulation of capsaicin-induced CGRP release in spinal cord slices and Dorsal Root Ganglia (DRG) neurons in culture after treatment with CB2 selective agonists. CB2 agonists are probably acting through several mechanisms and thus CB2 represents an interesting and promising target in the chronic pain field. Further clarification of the mechanisms at the basis of CB2 analgesic effect would surely be an intriguing and stimulating area of research for the years to come.
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PMID:[The cannabinoid system and pain: towards new drugs?]. 1935 15

Various stresses, which impair ER (endoplasmic reticulum) function, lead to an accumulation of unfolded or misfolded proteins. ER stress triggers many rescuer responses, including a UPR (unfolded protein response). Increasing evidence has suggested that ER stress is involved in neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and cerebral ischaemic insults), cancer, obesity and diabetes. In the present review, we consider the importance of ER stress under pathological conditions in mammals. Furthermore, we discuss the therapeutic potential for treatment targeting ER stress.
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PMID:Endoplasmic reticulum stress in disease: mechanisms and therapeutic opportunities. 1978 Jul 18

Ghrelin targets the hypothalamus to regulate food intake and adiposity. Endogenous ghrelin receptors [growth hormone secretagogue receptor (GHSR)] are also present in extrahypothalamic sites where they promote circuit activity associated with learning and memory, and reward seeking behavior. Here, we show that the substantia nigra pars compacta (SNpc), a brain region where dopamine (DA) cell degeneration leads to Parkinson's disease (PD), expresses GHSR. Ghrelin binds to SNpc cells, electrically activates SNpc DA neurons, increases tyrosine hydroxylase mRNA and increases DA concentration in the dorsal striatum. Exogenous ghrelin administration decreased SNpc DA cell loss and restricted striatal dopamine loss after 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine (MPTP) treatment. Genetic ablation of ghrelin or the ghrelin receptor (GHSR) increased SNpc DA cell loss and lowered striatal dopamine levels after MPTP treatment, an effect that was reversed by selective reactivation of GHSR in catecholaminergic neurons. Ghrelin-induced neuroprotection was dependent on the mitochondrial redox state via uncoupling protein 2 (UCP2)-dependent alterations in mitochondrial respiration, reactive oxygen species production, and biogenesis. Together, our data reveal that peripheral ghrelin plays an important role in the maintenance and protection of normal nigrostriatal dopamine function by activating UCP2-dependent mitochondrial mechanisms. These studies support ghrelin as a novel therapeutic strategy to combat neurodegeneration, loss of appetite and body weight associated with PD. Finally, we discuss the potential implications of these studies on the link between obesity and neurodegeneration.
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PMID:Ghrelin promotes and protects nigrostriatal dopamine function via a UCP2-dependent mitochondrial mechanism. 1990 54

Vibration biomechanical stimulation as the physiological basis of vibration physical exercises (whole body vibration) causes reflecting muscle contractions like tonic vibration reflex. This type of intervention leads to high intensive stimulation of proprioceptors as called muscle spindles which result in alteration in parameters of activity and developments of human physiological functions. This type of training has broad positive influence on organism. Acceleration physical exercises improve muscle performance, flexibility, nervous function, significantly increase bone mineral density, physiological secretion of anabolic hormones, growth and anti-aging factors; normalize/decrease cortisol as anti-stress effect and are beneficial for balance and mobility as well. It is showed acceleration training caused by vibration stimulus is beneficial for people suffering from osteoporosis and obesity, for rehabilitation of nervous and motor function in patients with Parkinson's disease, multiple sclerosis and stroke.
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PMID:[Vibrational physical exercises as the rehabilitation in gerontology]. 1994

The nociceptin opioid (NOP) receptor is the most recently discovered member of the family of the opioid receptors; its endogenous agonist is the peptide nociceptin. Due to the subsequent elucidation of its physiological role in both central and peripheral nervous system and in some non-neural tissues, there is a rapidly growing interest in the pharmacological application of substances active on this receptor. Despite the current clinical use of a morphinane-based NOP/MOP mixed ligand (buprenorphine) as an analgesic and in the treatment of drug addictions, so far just a few clinical trials have been made with selective NOP ligands. However, the perspective of their utilization is rapidly growing. Agonists can find applications in the treatment of neuropathic pain, anxiety, cough, drug addition, urinary incontinence, anorexia, congestive heart failure, hypertension; and antagonists for pain, depression, Parkinson's disease, obesity, and as memory enhancers. Besides peptide ligands, which are still subjected to many pharmacological investigations, many different chemical classes of NOP ligands have been discovered: piperidines, nortropanes, spiropiperidines, 4-amino-quinolines and quinazolines, and others. The new advances in establishing structure-activity relationships, also with the help of modeling studies, can permit the development of more active and selective molecules.
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PMID:Development of nociceptin receptor (NOP) agonists and antagonists. 2009 19

Clinical and experimental observations show individual differences in the development of addiction. Increasing evidence supports the hypothesis that dopamine receptor availability in the nucleus accumbens (NAc) predisposes drug reinforcement. Here, modeling striatal-midbrain dopaminergic circuit, we propose a reinforcement learning model for addiction based on the actor-critic model of striatum. Modeling dopamine receptors in the NAc as modulators of learning rate for appetitive--but not aversive--stimuli in the critic--but not the actor--we define vulnerability to addiction as a relatively lower learning rate for the appetitive stimuli, compared to aversive stimuli, in the critic. We hypothesize that an imbalance in this learning parameter used by appetitive and aversive learning systems can result in addiction. We elucidate that the interaction between the degree of individual vulnerability and the duration of exposure to drug has two progressive consequences: deterioration of the imbalance and establishment of an abnormal habitual response in the actor. Using computational language, the proposed model describes how development of compulsive behavior can be a function of both degree of drug exposure and individual vulnerability. Moreover, the model describes how involvement of the dorsal striatum in addiction can be augmented progressively. The model also interprets other forms of addiction, such as obesity and pathological gambling, in a common mechanism with drug addiction. Finally, the model provides an answer for the question of why behavioral addictions are triggered in Parkinson's disease patients by D2 dopamine agonist treatments.
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PMID:Individual differences in nucleus accumbens dopamine receptors predict development of addiction-like behavior: a computational approach. 2056 76


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