-
Archivos Argentinos de Pediatria Aug 2023Network communication digital platforms have revolutionized the way we communicate, get information, and entertain ourselves; they have had a major impact on the new... (Review)
Review
Network communication digital platforms have revolutionized the way we communicate, get information, and entertain ourselves; they have had a major impact on the new generations. The pandemic has increased consumption patterns at all ages and its consequences: a sedentary lifestyle, obesity, sleep, psychological, cognitive, memory/attention, and academic performance disorders, problematic behaviors, and risks of cyberbullying. The activity of the new generations on TikTok -a platform that allows them to create, view, share videos and viral challenges- has affected their behavior. Their posts lead to likes, comments, and followers; this stimulates the dopaminergic reward system, which is the basis of addictive behaviors. Pediatricians should be aware of these behaviors in order to recommend good practices. The objective of this narrative review, based on the bibliography from PubMed Central, SciELO, national and international recommendations, is to provide information and an update to health care providers on TikTok, its characteristics, and the recommendations for safe use.
Topics: Humans; Adolescent; Child; Social Media; Academic Performance; Behavior, Addictive; Communication; Dopamine
PubMed: 36692353
DOI: 10.5546/aap.2022-02674.eng -
Annual Review of Pathology Jan 2024Dystonia is a clinically and genetically highly heterogeneous neurological disorder characterized by abnormal movements and postures caused by involuntary sustained or... (Review)
Review
Dystonia is a clinically and genetically highly heterogeneous neurological disorder characterized by abnormal movements and postures caused by involuntary sustained or intermittent muscle contractions. A number of groundbreaking genetic and molecular insights have recently been gained. While they enable genetic testing and counseling, their translation into new therapies is still limited. However, we are beginning to understand shared pathophysiological pathways and molecular mechanisms. It has become clear that dystonia results from a dysfunctional network involving the basal ganglia, cerebellum, thalamus, and cortex. On the molecular level, more than a handful of, often intertwined, pathways have been linked to pathogenic variants in dystonia genes, including gene transcription during neurodevelopment (e.g., , ), calcium homeostasis (e.g., , ), striatal dopamine signaling (e.g., ), endoplasmic reticulum stress response (e.g., , , ), autophagy (e.g., ), and others. Thus, different forms of dystonia can be molecularly grouped, which may facilitate treatment development in the future.
Topics: Humans; Dystonia; Dystonic Disorders; Dopamine; Molecular Chaperones; DNA-Binding Proteins; Apoptosis Regulatory Proteins; Anoctamins
PubMed: 37738511
DOI: 10.1146/annurev-pathmechdis-051122-110756 -
Nature Sep 2023Striatal dopamine and acetylcholine are essential for the selection and reinforcement of motor actions and decision-making. In vitro studies have revealed an...
Striatal dopamine and acetylcholine are essential for the selection and reinforcement of motor actions and decision-making. In vitro studies have revealed an intrastriatal circuit in which acetylcholine, released by cholinergic interneurons (CINs), drives the release of dopamine, and dopamine, in turn, inhibits the activity of CINs through dopamine D2 receptors (D2Rs). Whether and how this circuit contributes to striatal function in vivo is largely unknown. Here, to define the role of this circuit in a living system, we monitored acetylcholine and dopamine signals in the ventrolateral striatum of mice performing a reward-based decision-making task. We establish that dopamine and acetylcholine exhibit multiphasic and anticorrelated transients that are modulated by decision history and reward outcome. Dopamine dynamics and reward encoding do not require the release of acetylcholine by CINs. However, dopamine inhibits acetylcholine transients in a D2R-dependent manner, and loss of this regulation impairs decision-making. To determine how other striatal inputs shape acetylcholine signals, we assessed the contribution of cortical and thalamic projections, and found that glutamate release from both sources is required for acetylcholine release. Altogether, we uncover a dynamic relationship between dopamine and acetylcholine during decision-making, and reveal multiple modes of CIN regulation. These findings deepen our understanding of the neurochemical basis of decision-making and behaviour.
Topics: Animals; Mice; Acetylcholine; Corpus Striatum; Dopamine; Glutamic Acid; Neostriatum; Decision Making; Reward; Receptors, Dopamine D2; Cholinergic Neurons; Neural Pathways
PubMed: 37557915
DOI: 10.1038/s41586-023-06492-9 -
Neuron Nov 2023A genetically valid animal model could transform our understanding of schizophrenia (SCZ) disease mechanisms. Rare heterozygous loss-of-function (LoF) mutations in...
A genetically valid animal model could transform our understanding of schizophrenia (SCZ) disease mechanisms. Rare heterozygous loss-of-function (LoF) mutations in GRIN2A, encoding a subunit of the NMDA receptor, greatly increase the risk of SCZ. By transcriptomic, proteomic, and behavioral analyses, we report that heterozygous Grin2a mutant mice show (1) large-scale gene expression changes across multiple brain regions and in neuronal (excitatory and inhibitory) and non-neuronal cells (astrocytes and oligodendrocytes), (2) evidence of hypoactivity in the prefrontal cortex (PFC) and hyperactivity in the hippocampus and striatum, (3) an elevated dopamine signaling in the striatum and hypersensitivity to amphetamine-induced hyperlocomotion (AIH), (4) altered cholesterol biosynthesis in astrocytes, (5) a reduction in glutamatergic receptor signaling proteins in the synapse, and (6) an aberrant locomotor pattern opposite of that induced by antipsychotic drugs. These findings reveal potential pathophysiologic mechanisms, provide support for both the "hypo-glutamate" and "hyper-dopamine" hypotheses of SCZ, and underscore the utility of Grin2a-deficient mice as a genetic model of SCZ.
Topics: Animals; Mice; Brain; Dopamine; Neuroglia; Neurons; Prefrontal Cortex; Proteomics; Disease Models, Animal; Receptors, N-Methyl-D-Aspartate
PubMed: 37657442
DOI: 10.1016/j.neuron.2023.08.004 -
Nature Communications Sep 2023Prosaposin (PSAP) modulates glycosphingolipid metabolism and variants have been linked to Parkinson's disease (PD). Here, we find altered PSAP levels in the plasma, CSF...
Prosaposin (PSAP) modulates glycosphingolipid metabolism and variants have been linked to Parkinson's disease (PD). Here, we find altered PSAP levels in the plasma, CSF and post-mortem brain of PD patients. Altered plasma and CSF PSAP levels correlate with PD-related motor impairments. Dopaminergic PSAP-deficient (cPSAP) mice display hypolocomotion and depression/anxiety-like symptoms with mildly impaired dopaminergic neurotransmission, while serotonergic PSAP-deficient (cPSAP) mice behave normally. Spatial lipidomics revealed an accumulation of highly unsaturated and shortened lipids and reduction of sphingolipids throughout the brains of cPSAP mice. The overexpression of α-synuclein via AAV lead to more severe dopaminergic degeneration and higher p-Ser129 α-synuclein levels in cPSAP mice compared to WT mice. Overexpression of PSAP via AAV and encapsulated cell biodelivery protected against 6-OHDA and α-synuclein toxicity in wild-type rodents. Thus, these findings suggest PSAP may maintain dopaminergic lipid homeostasis, which is dysregulated in PD, and counteract experimental parkinsonism.
Topics: Animals; Mice; alpha-Synuclein; Dopamine; Dopaminergic Neurons; Parkinson Disease; Saposins; Sphingolipids
PubMed: 37726325
DOI: 10.1038/s41467-023-41539-5 -
Australian Journal of General Practice Sep 2023Restless legs syndrome (RLS) is a common sensorimotor disorder causing significant distress and is commonly seen in the primary care setting.
BACKGROUND
Restless legs syndrome (RLS) is a common sensorimotor disorder causing significant distress and is commonly seen in the primary care setting.
OBJECTIVE
This article outlines the epidemiology, pathophysiology, diagnosis and management of RLS, with a focus on the primary care setting.
DISCUSSION
RLS is a clinical diagnosis, although mimics exist. Brain iron deficiency, dopaminergic dysfunction and genetics underpin the poorly understood pathophysiology of this common condition. After repleting iron stores, reviewing any exacerbating medications and attending to non-pharmacological management options, there are pharmacological options that prove to be effective, although with class-specific effects that need to be considered.
Topics: Humans; Restless Legs Syndrome; Dopamine; Iron Deficiencies
PubMed: 37666782
DOI: 10.31128/AJGP-02-23-6722 -
EBioMedicine Jul 2023Glucagon-like peptide1 receptor (GLP-1R) agonists have been found to reduce alcohol drinking in rodents and overweight patients with alcohol use disorder (AUD). However,...
BACKGROUND
Glucagon-like peptide1 receptor (GLP-1R) agonists have been found to reduce alcohol drinking in rodents and overweight patients with alcohol use disorder (AUD). However, the probability of low semaglutide doses, an agonist with higher potency and affinity for GLP-1R, to attenuate alcohol-related responses in rodents and the underlying neuronal mechanisms is unknown.
METHODS
In the intermittent access model, we examined the ability of semaglutide to decrease alcohol intake and block relapse-like drinking, as well as imaging the binding of fluorescently marked semaglutide to nucleus accumbens (NAc) in both male and female rats. The suppressive effect of semaglutide on alcohol-induced locomotor stimulation and in vivo dopamine release in NAc was tested in male mice. We evaluated effect of semaglutide on the in vivo release of dopamine metabolites (DOPAC and HVA) and gene expression of enzymes metabolising dopamine (MAOA and COMT) in male mice.
FINDINGS
In male and female rats, acute and repeated semaglutide administration reduced alcohol intake and prevented relapse-like drinking. Moreover, fluorescently labelled semaglutide was detected in NAc of alcohol-drinking male and female rats. Further, semaglutide attenuated the ability of alcohol to cause hyperlocomotion and to elevate dopamine in NAc in male mice. As further shown in male mice, semaglutide enhanced DOPAC and HVA in NAc when alcohol was onboard and increased the gene expression of COMT and MAOA.
INTERPRETATION
Altogether, this indicates that semaglutide reduces alcohol drinking behaviours, possibly via a reduction in alcohol-induced reward and NAc dependent mechanisms. As semaglutide also decreased body weight of alcohol-drinking rats of both sexes, upcoming clinical studies should test the plausibility that semaglutide reduces alcohol intake and body weight in overweight AUD patients.
FUNDING
Swedish Research Council (2019-01676), LUA/ALF (723941) from the Sahlgrenska University Hospital and the Swedish brain foundation.
Topics: Female; Rats; Mice; Male; Animals; Exenatide; Dopamine; 3,4-Dihydroxyphenylacetic Acid; Overweight; Ethanol; Alcoholism; Alcohol Drinking; Recurrence
PubMed: 37295046
DOI: 10.1016/j.ebiom.2023.104642 -
Brain Research Bulletin Jul 2023Impairments in systematic and regional glucose metabolism exist in patients with Parkinson's disease (PD) at every stage of the disease course, and such impairments are... (Review)
Review
Impairments in systematic and regional glucose metabolism exist in patients with Parkinson's disease (PD) at every stage of the disease course, and such impairments are associated with the incidence, progression, and special phenotypes of PD, which affect each physiological process of glucose metabolism including glucose uptake, glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and pentose phosphate shunt pathway. These impairments may be attributed to various mechanisms, such as insulin resistance, oxidative stress, abnormal glycated modification, blood-brain-barrier dysfunction, and hyperglycemia-induced damages. These mechanisms could subsequently cause excessive methylglyoxal and reactive oxygen species production, neuroinflammation, abnormal aggregation of protein, mitochondrial dysfunction, and decreased dopamine, and finally result in energy supply insufficiency, neurotransmitter dysregulation, aggregation and phosphorylation of α-synuclein, and dopaminergic neuron loss. This review discusses the glucose metabolism impairment in PD and its pathophysiological mechanisms, and briefly summarized the currently-available therapies targeting glucose metabolism impairment in PD, including glucagon-likepeptide-1 (GLP-1) receptor agonists and dual GLP-1/gastric inhibitory peptide receptor agonists, metformin, and thiazoledinediones.
Topics: Humans; Parkinson Disease; Hyperglycemia; Glycolysis; Dopamine; Glucose; Glucagon-Like Peptide 1; Dopaminergic Neurons
PubMed: 37210012
DOI: 10.1016/j.brainresbull.2023.110672 -
Annual Review of Vision Science Sep 2023Although diabetic retinopathy (DR) is clinically diagnosed as a vascular disease, many studies find retinal neuronal and visual dysfunction before the onset of vascular... (Review)
Review
Although diabetic retinopathy (DR) is clinically diagnosed as a vascular disease, many studies find retinal neuronal and visual dysfunction before the onset of vascular DR. This suggests that DR should be viewed as a neurovascular disease. Prior to the onset of DR, human patients have compromised electroretinograms that indicate a disruption of normal function, particularly in the inner retina. They also exhibit reduced contrast sensitivity. These early changes, especially those due to dysfunction in the inner retina, are also seen in rodent models of diabetes in the early stages of the disease. Rodent models of diabetes exhibit several neuronal mechanisms, such as reduced evoked GABA release, increased excitatory glutamate signaling, and reduced dopamine signaling, that suggest specific neuronal deficits. This suggests that understanding neuronal deficits may lead to early diabetes treatments to ameliorate neuronal dysfunction.
Topics: Humans; Diabetic Retinopathy; Retina; Vision Disorders; Dopamine; Retinal Neurons; Diabetes Mellitus
PubMed: 37164027
DOI: 10.1146/annurev-vision-111022-123810 -
Cell Reports Oct 2023Dopamine synapses play a crucial role in volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and...
Dopamine synapses play a crucial role in volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and neurological disorders. Despite this significance, the true biological nature of dopamine synapses remains poorly understood. Here, we show that dopamine transmission is strongly correlated with GABA co-transmission across the brain and dopamine synapses are structured and function like GABAergic synapses with marked regional heterogeneity. In addition, GABAergic-like dopamine synapses are clustered on the dendrites, and GABA transmission at dopamine synapses has distinct physiological properties. Interestingly, the knockdown of neuroligin-2, a key postsynaptic protein at GABAergic synapses, unexpectedly does not weaken GABA co-transmission but instead facilitates it at dopamine synapses in the striatal neurons. More importantly, the attenuation of GABA co-transmission precedes deficits in dopaminergic transmission in animal models of Parkinson's disease. Our findings reveal the spatial and functional nature of GABAergic-like dopamine synapses in health and disease.
Topics: Animals; Dopamine; Brain; Synapses; Neurons; gamma-Aminobutyric Acid; Receptors, GABA-A
PubMed: 37819757
DOI: 10.1016/j.celrep.2023.113239