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Acta Neuropsychiatrica Feb 2021Vitamin D deficiency may be a clinical problem in patients with addictions. The authors systematically searched for studies addressing vitamin D and addiction and...
OBJECTIVE
Vitamin D deficiency may be a clinical problem in patients with addictions. The authors systematically searched for studies addressing vitamin D and addiction and develop a hypothesis which can direct future research of the possible mechanistic role of vitamin D in the process of addiction.
METHODS
Systematic review of the literature found in PubMed and EMBASE followed by narrative review combined with clinical experiences leading to hypotheses for future research.
RESULTS
Only five articles were identified about a role of vitamin D in the pathophysiology of addiction. Their results are in line with a possible influence of vitamin D in dopaminergic transmission. The cerebral vitamin D status depends on the functionality of genetic variants of vitamin D receptor and other involved genes. Routine serum calcidiol levels may not adequately reflect cerebral vitamin D status. Uncertainty exists regarding appropriate calcidiol blood levels and proper dosages for affecting the central nervous system (CNS).
CONCLUSIONS
The putative pathophysiological role of vitamin D in substance abuse has been insufficiently studied which calls to more studies how to measure cerebral vitamin D status in clinical practice. Research is indicated whether vitamin D supplementation should use higher dosages and aim to reach higher calcidiol serum levels. Measuring dopaminergic functioning within the prefrontal cortex as reflected by neuropsychological tests selected as suitable could be a appropriate proxy for the cerebral vitamin D status when studying the pharmacogenomics of this functionality in patients.
Topics: Adult; Alcoholism; Animals; Behavior, Addictive; Calcifediol; Central Nervous System; Dopaminergic Neurons; Female; Humans; Male; Middle Aged; Models, Animal; Pharmacogenetics; Polymorphism, Single Nucleotide; Rats; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency
PubMed: 33183376
DOI: 10.1017/neu.2020.41 -
Basic & Clinical Pharmacology &... Jul 2024Parkinson's disease (PD) is a neurodegenerative disease that affects dopaminergic neurons, thus impairing dopaminergic signalling. Quercetin (QUE) has antioxidant and...
Parkinson's disease (PD) is a neurodegenerative disease that affects dopaminergic neurons, thus impairing dopaminergic signalling. Quercetin (QUE) has antioxidant and neuroprotective properties that are promising for the treatment of PD. This systematic review aimed to investigate the therapeutic effects of QUE against PD in preclinical models. The systematic search was performed in PubMed, Scopus and Web of Science. At the final screening stage, 26 articles were selected according to pre-established criteria. Selected studies used different methods for PD induction, as well as animal models. Most studies used rats (73.08%) and mice (23.08%), with 6-OHDA as the main strategy for PD induction (38.6%), followed by rotenone (30.8%). QUE was tested immersed in oil, nanosystems or in free formulations, in varied routes of administration and doses, ranging from 10 to 400 mg/kg and from 5 to 200 mg/kg in oral and intraperitoneal administrations, respectively. Overall, evidence from published data suggests a potential use of QUE as a treatment for PD, mainly through the inhibition of oxidative stress, neuroinflammatory response and apoptotic pathways.
Topics: Animals; Humans; Mice; Rats; Antioxidants; Apoptosis; Disease Models, Animal; Neuroprotective Agents; Oxidative Stress; Oxidopamine; Parkinson Disease; Parkinsonian Disorders; Quercetin; Rotenone
PubMed: 38682342
DOI: 10.1111/bcpt.14011 -
Neuroscience and Biobehavioral Reviews Aug 2018Pathological aggression, frequently observed in psychiatric patients and criminal subjects, poses a major burden on the health care and criminal justice system,...
Pathological aggression, frequently observed in psychiatric patients and criminal subjects, poses a major burden on the health care and criminal justice system, necessitating better aetiological models to inform targets for prevention and intervention. Emerging evidence suggests that adverse experiences during development can cause long-lasting brain alterations associated with maladaptive behaviors, such as aggression. The present review discusses, mainly based on studies in rodents, whether disruption of the mesocorticolimbic dopamine system through chronic stress-exposure during adolescence predisposes to adult aggression. Our findings suggest that chronic stress in adolescence induces prefrontal cortex (PFC) hyperdopaminergia and ultimately leads to blunted prefrontal dopamine transmission in adulthood. This, in turn, disrupts the ability of the PFC to guide adaptive, long-term focused action selection by regulating mesolimbic dopamine signaling. We propose that, especially during the dynamic and transitional period of adolescence, exposure to chronic stress could lead to excessive adaptive change, which may result in an increased vulnerability to maladaptive aggression in adulthood. We discuss how these findings in rodents may translate to humans.
Topics: Aggression; Aging; Animals; Brain; Dopaminergic Neurons; Rodentia; Stress, Psychological
PubMed: 27826069
DOI: 10.1016/j.neubiorev.2016.10.009 -
BMC Medical Genetics Mar 2006Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory.
METHODS
We analyzed three NAT2 genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects and 124 PD patients for these genetic variations. Further, we have undertaken a systematic review of NAT2 studies on PD and we incorporated our results in a meta-analysis consisting of 10 studies, 1,206 PD patients and 1,619 control subjects.
RESULTS
Overall, we did not find significant differences in polymorphic acetylation genotypes in PD and control subjects. In the meta-analysis of slow acetylators from 10 studies and representing 604/1206 PD vs. 732/1619 control subjects, a marginally significant odds ratio (OR) of 1.32 (95% CI 1.12-1.54, p < 0.05) was obtained. Re-analysis of the data to exclude the only two studies showing positive association of slow acetylators to PD, resulted in a non-significant OR (1.07, 95% CI 0.9-1.28). Furthermore, meta-analysis of studies for c.590G>A, where both allele and genotype frequencies in PD vs. control subjects were analyzed, did not give significant summary odds ratios as well.
CONCLUSION
We found little evidence for differences in polymorphic acetylation genotypes in PD and control subjects. Results of the meta-analyses did not also provide conclusive evidence for an overall association of NAT2 slow acetylator genotypes to PD.
Topics: Arylamine N-Acetyltransferase; Case-Control Studies; Gene Frequency; Genetic Predisposition to Disease; Humans; Parkinson Disease; Polymorphism, Single Nucleotide
PubMed: 16571112
DOI: 10.1186/1471-2350-7-30 -
International Journal of Molecular... Aug 2021Neonicotinoids are a class of insecticides that exert their effect through a specific action on neuronal nicotinic acetylcholine receptors (nAChRs). The success of these...
Neonicotinoids are a class of insecticides that exert their effect through a specific action on neuronal nicotinic acetylcholine receptors (nAChRs). The success of these insecticides is due to this mechanism of action, since they act as potent agonists of insect nAChRs, presenting low affinity for vertebrate nAChRs, which reduces potential toxic risk and increases safety for non-target species. However, although neonicotinoids are considered safe, their presence in the environment could increase the risk of exposure and toxicity. On the other hand, although neonicotinoids have low affinity for mammalian nAChRs, the large quantity, variety, and ubiquity of these receptors, combined with its diversity of functions, raises the question of what effects these insecticides can produce in non-target species. In the present systematic review, we investigate the available evidence on the biochemical and behavioral effects of neonicotinoids on the mammalian nervous system. In general, exposure to neonicotinoids at an early age alters the correct neuronal development, with decreases in neurogenesis and alterations in migration, and induces neuroinflammation. In adulthood, neonicotinoids induce neurobehavioral toxicity, these effects being associated with their modulating action on nAChRs, with consequent neurochemical alterations. These alterations include decreased expression of nAChRs, modifications in acetylcholinesterase activity, and significant changes in the function of the nigrostriatal dopaminergic system. All these effects can lead to the activation of a series of intracellular signaling pathways that generate oxidative stress, neuroinflammation and, finally, neuronal death. Neonicotinoid-induced changes in nAChR function could be responsible for most of the effects observed in the different studies.
Topics: Animals; Humans; Insecticides; Mammals; Neonicotinoids; Neurons; Receptors, Nicotinic
PubMed: 34445117
DOI: 10.3390/ijms22168413 -
Frontiers in Aging Neuroscience 2021Parkinson's disease (PD) is one of the most common neurodegenerative maladies with unforeseen complex pathologies. While this neurodegenerative disorder's neuropathology...
Failure of Glial Cell-Line Derived Neurotrophic Factor (GDNF) in Clinical Trials Orchestrated By Reduced NR4A2 (NURR1) Transcription Factor in Parkinson's Disease. A Systematic Review.
Parkinson's disease (PD) is one of the most common neurodegenerative maladies with unforeseen complex pathologies. While this neurodegenerative disorder's neuropathology is reasonably well known, its etiology remains a mystery, making it challenging to aim therapy. Glial cell-line derived neurotrophic factor (GDNF) remains an auspicious therapeutic molecule for treating PD. Neurotrophic factor derived from glial cell lines is effective in rodents and nonhuman primates, but clinical findings have been equivocal. Laborious exertions have been made over the past few decades to improve and assess GDNF in treating PD (clinical studies). Definitive clinical trials have, however, failed to demonstrate a survival advantage. Consequently, there seemed to be a doubt as to whether GDNF has merit in the potential treatment of PD. The purpose of this cutting edge review is to speculate as to why the clinical trials have failed to meet the primary endpoint. We introduce a hypothesis, "Failure of GDNF in clinical trials succumbed by nuclear receptor-related factor 1 (Nurr1) shortfall." We demonstrate how Nurr1 binds to GDNF to induce dopaminergic neuron synthesis. Due to its undisputable neuro-protection aptitude, we display Nurr1 (also called Nr4a2) as a promising therapeutic target for PD.
PubMed: 33716718
DOI: 10.3389/fnagi.2021.645583 -
Expert Opinion on Pharmacotherapy Dec 2020Parkinson's disease (PD) is a progressive, chronic neurodegenerative disorder. The main neuropathological cause of the disease is the death of dopaminergic neurons in...
INTRODUCTION
Parkinson's disease (PD) is a progressive, chronic neurodegenerative disorder. The main neuropathological cause of the disease is the death of dopaminergic neurons in the substantia nigra. Unfortunately, there is no curative treatment yet. The gold-standard of the treatment is levodopa (LD). During the course of the disease, motor complications develop, which postulates the addition of entacapone (ENT) to the dopaminergic medication. Previous studies have suggested that patients have a better quality of life when entacapone is added in a combination with LD.
AREAS COVERED
A systematic literature search was performed. Articles were identified through PubMed (MEDLINE), Web of Science, Ovid, and ClinicalTrials.gov databases. The following search terms were used: 'Levodopa' AND 'Carbidopa' OR 'Benserazide' AND 'Entacapone'. The search period was between 2000 and 2020. Twenty randomized and 10 non-randomized clinical trials (12,893 subjects) were included in the qualitative analysis. The systematic review was written in line with the PRISMA guideline.
EXPERT OPINION
ENT administered in combination with LD resulted in a better quality of life compared to separate tablets. Therefore, in PD patients where impaired motor performance develops and the application of entacapone is necessary, it is suggested to be administered in a single tablet form.
Topics: Antiparkinson Agents; Catechols; Drug Combinations; Humans; Levodopa; Motor Activity; Nitriles; Parkinson Disease; Quality of Life; Randomized Controlled Trials as Topic; Tablets
PubMed: 32808807
DOI: 10.1080/14656566.2020.1806237 -
Journal of Clinical Neuroscience :... Jul 2019Functional magnetic resonance imaging (fMRI) is a non-invasive imaging modality that enables the assessment of neural connectivity and oxygen utility of the brain using... (Meta-Analysis)
Meta-Analysis
Functional magnetic resonance imaging (fMRI) is a non-invasive imaging modality that enables the assessment of neural connectivity and oxygen utility of the brain using blood oxygen level dependent (BOLD) imaging sequence. Electroencephalography (EEG), on the other hands, looks at cortical electrical impulses of the brain thus detecting brainwave patterns during rest and thought processing. The combination of these two modalities is called fMRI with simultaneous EEG (fMRI-EEG), which has emerged as a new tool for experimental neuroscience assessments and has been applied clinically in many settings, most commonly in epilepsy cases. Recent advances in imaging has led to fMRI-EEG being utilized in behavioural studies which can help in giving an objective assessment of ambiguous cases and help in the assessment of response to treatment by providing a non-invasive biomarker of the disease processes. We aim to review the role and interpretation of fMRI-EEG in studies pertaining to psychiatric disorders and behavioral abnormalities.
Topics: Adult; Brain; Brain Mapping; Brain Waves; Dopaminergic Neurons; Electroencephalography; Epilepsy; Humans; Magnetic Resonance Imaging; Male; Oxygen; Rest
PubMed: 30955950
DOI: 10.1016/j.jocn.2019.03.054