Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opiate addiction is a central nervous system disorder of unknown mechanism. Neuronal basis of positive reinforcement, which is essential to the action of opioids, relies on activation of dopaminergic neurons resulting in an increased dopamine release in the mesolimbic brain structures. Certain aspects of opioid dependence and withdrawal syndrome are also related to the activity of noradrenergic and serotonergic systems, as well as to both excitatory and inhibitory amino acid and peptidergic systems. The latter pathways have been recently proven to be involved both in the development of dependence and in counteracting the states related to relapse. An important role in neurochemical mechanisms of opioid reward, dependence and vulnerability to addiction has been ascribed to endogenous opioid peptides, particularly those acting via the mu- and kappa-opioid receptors. Opiate abuse leads to adaptive reactions in the nervous system which occur at the cellular and molecular levels. Recent research indicates that intracellular mechanisms of signal transmission-from the receptor, through G proteins, cyclic AMP, MAP kinases to transcription factors--also play an important role in opioid tolerance and dependence. The latter link in this chain of reactions may modify synthesis of target genes and in this manner, it may be responsible for opiate-induced long-lasting neural plasticity.
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PMID:Opioid abuse and brain gene expression. 1546 44

The neuropeptides orexin A and B (hypocretin-1 and -2) are involved in numerous central regulation processes such as energy homeostasis, sleeping behaviour and addiction. The expression of orexins and orexin receptors in a variety of tissues outside the brain and the presence of orexin A in the circulation indicate the existence of an additional peripheral orexin system. Furthermore, it is well established that orexins exert an influence on the regulation of the hypothalamus-pituitary-adrenal axis, acting both on its central and peripheral branch. In rat and human adrenal cortices the expression of both orexin receptors has been verified with a predominance of OX(2)R. The local expression of orexin receptors was observed to be gender specific and to be modified by plasma glucose and insulin concentrations, nutritional status as well as gonadal steroids. Various studies consistently demonstrated orexin A to enhance glucocorticoid secretion of rat and human adrenal cortices, while orexin B was found to be either less potent or ineffective. On the contrary, the influence of orexins on adrenocortical aldosterone production and cell proliferation is still more controversial. Recent findings indicate that orexins stimulate adrenocortical steroidogenesis by augmenting transcription of selective steroidogenic enzymes and proteins such as steroidogenic acute regulatory protein. Both, G(q) and G(s), signalling pathways with a downstream activation of MAP kinases appear to be involved in this regulation.
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PMID:Interactions of orexins/hypocretins with adrenocortical functions. 1971 97

Exercise is known to be rewarding and have positive effects on mental and physical health. Excessive exercise, however, can be the result of an underlying behavioral/physiological addiction. Both humans who exercise regularly and rodent models of exercise addiction sometimes display behavioral withdrawal symptoms, including depression and anxiety, when exercise is denied. However, few studies have examined the physiological state that occurs during this withdrawal period. Alterations in blood pressure (BP) are common physiological indicators of withdrawal in a variety of addictions. In this study, we examined exercise withdrawal in four replicate lines of mice selectively bred for high voluntary wheel running (HR lines). Mice from the HR lines run almost 3-fold greater distances on wheels than those from non-selected control lines, and have altered brain activity as well as increased behavioral despair when wheel access is removed. We tested the hypothesis that male HR mice have an altered cardiovascular response (heart rate, systolic, diastolic, and mean arterial pressure [MAP]) during exercise withdrawal. Measurements using an occlusion tail-cuff system were taken during 8 days of baseline, 6 days of wheel access, and 2 days of withdrawal (wheel access blocked). During withdrawal, HR mice had significantly lower systolic BP, diastolic BP, and MAP than controls, potentially indicating a differential dependence on voluntary wheel running in HR mice. This is the first characterization of a cardiovascular withdrawal response in an animal model of high voluntary exercise.
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PMID:Mice from lines selectively bred for high voluntary wheel running exhibit lower blood pressure during withdrawal from wheel access. 2345 32

New neurons are generated in the hippocampus each day and their survival is greatly enhanced through effortful learning (Shors, 2014). The numbers of cells produced can be increased by physical exercise (van Praag, Kempermann, & Gage, 1999). These findings inspired us to develop a clinical intervention for humans known as Mental and Physical Training, or MAP Training. Each session consists of 30min of mental training with focused attention meditation (20min sitting and 10min walking). Meditation is an effortful training practice that involves learning about the transient nature of thoughts and thought patterns, and acquiring skills to recognize them without necessarily attaching meaning and/or emotions to them. The mental training component is followed by physical training with 30min of aerobic exercise performed at moderate intensity. During this component, participants learn choreographed dance routines while engaging in aerobic exercise. In a pilot "proof-of-concept" study, we provided supervised MAP Training (2 sessions per week for 8weeks) to a group of young mothers in the local community who were recently homeless, most of them having previously suffered from physical and sexual abuse, addiction, and depression. Preliminary data suggest that MAP Training improves dependent measures of aerobic fitness (as assessed by maximal rate of oxygen consumed) while decreasing symptoms of depression and anxiety. Similar changes were not observed in a group of recently homeless women who did not participate in MAP Training. It is not currently possible to determine whether new neurons in the human brain increase in number as a result of MAP Training. Rather these preliminary results of MAP Training illustrate how neuroscientific research can be translated into novel clinical interventions that benefit human health and wellness.
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PMID:Mental and Physical (MAP) Training: a neurogenesis-inspired intervention that enhances health in humans. 2521 4

Methamphetamine (MA)-related psychiatric symptoms (MAP) are serious comorbidities of MA use and result in many social problems such as violence and suicide. We investigated the sociodemographic and genetic risk factors for persistent MAP of MA users (MUs) and constructed an early MAP prediction model. Derivation and replication samples had 1734 and 905 MUs, respectively. Symptom Checklist 90, Childhood Trauma Questionnaire, Attention-Deficit Hyperactivity Disorder (ADHD) Rating Scale-IV, and Social Support Rating Scale were used to assess the past-year prevalence of general MAP and life events retrospectively. Genome-wide association study (GWAS) was used to analyze MAP-related genetic factors. The prediction model was constructed by integrating the risk life events and clinical and genetic features using logistic regression. Of the 2639 MUs, 1293 (48.83%) had past-year MAP. The severity of MA addiction (SMA), childhood trauma, childhood ADHD symptoms, and social support were reliable risk factors for persistent MAP. By integrating these risk factors and the polygenic risk score from GWAS from derivation samples, the area under the curve (AUC) of the predictive model for MAP was 0.754 (95% CI 0.717~0.771). The risk factors and prediction model were also verified in replication samples. In addition, SMA, ADHD, and social support were mediators for the effect of the risk genetic factor on persistent MAP. Our study identified several risk factors for persistent MAP and will be helpful for developing scalable tools for the prevention of persistent and general MAP.
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PMID:Risk factors and an early prediction model for persistent methamphetamine-related psychiatric symptoms. 3119 8