The Synaptic and Circuit Functions of Vitamin D in Neurodevelopment Disorders

Neuropsychiatric Disease and Treatment, Journal Year: 2023, Volume and Issue: Volume 19, P. 1515 - 1530

Published: July 1, 2023

Vitamin D deficiency/insufficiency is a public health issue around the world.According to epidemiological studies, low vitamin levels have been associated with an increased risk of some neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit hyperactivity (ADHD).Animal models reveal that has variety impacts on synapses circuits in brain.A lack affects expression synaptic proteins, as well synthesis metabolism various neurotransmitters.Depending where receptors (VDRs) are expressed, may also regulate certain neuronal through endocannabinoid signaling, mTOR pathway oxytocin signaling.While inconsistently, data suggest supplementation be able reduce core symptoms ASD ADHD.This review emphasizes D's role circuit mechanisms disorders ADHD.Future application these will depend both basic research clinical order make transition from bench bedside.

Language: Английский

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Altered neurotransmission in stress-induced depressive disorders: The underlying role of the amygdala in depression

Neuropeptides, Journal Year: 2023, Volume and Issue: 98, P. 102322 - 102322

Published: Jan. 20, 2023

Language: Английский

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Divergent projections of the prelimbic cortex mediate autism- and anxiety-like behaviors

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(6), P. 2343 - 2354

Published: Jan. 23, 2023

The comorbidity of autism spectrum disorder and anxiety is common, but the underlying circuitry poorly understood. Here, Tmem74

Language: Английский

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Advances in understanding meso‐cortico‐limbic‐striatal systems mediating risky reward seeking

Journal of Neurochemistry, Journal Year: 2021, Volume and Issue: 157(5), P. 1547 - 1571

Published: March 11, 2021

The risk of an aversive consequence occurring as the result a reward-seeking action can have profound effect on subsequent behavior. Such events be described punishers, they decrease probability that same will produced again in future and increase exploration less risky alternatives. Punishment involve omission expected rewarding event ("negative" punishment) or addition unpleasant ("positive" punishment). Although many individuals adaptively navigate situations associated with negative positive punishment, those suffering from substance use disorders behavioral addictions tend to able curtail addictive behaviors despite consequences them. Here, we discuss psychological processes underpinning reward seeking punishment consider how assays animals been employed provide insights into neural mechanisms underlying disorders. We then review critical contributions dopamine signaling learning seeking, address roles interconnected ventral striatal, cortical, amygdala regions these processes. conclude by discussing ample opportunities for study clarify gaps literature, particularly related delineating distinct phases decision-making process.

Language: Английский

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Neural Circuits for Social Interactions: From Microcircuits to Input-Output Circuits

Frontiers in Neural Circuits, Journal Year: 2021, Volume and Issue: 15

Published: Oct. 29, 2021

Social behaviors entail responses to social information and requires the perception integration of cues through a complex cognition process that involves attention, memory, motivation, emotion. Neurobiological molecular mechanisms underlying behavior are highly conserved across species, inter- intra-specific variability observed in can be explained large extent by differential activity neural network. However, microcircuits precise networks involved remain mysterious. In this review, we summarize input-output circuits on molecular, cellular, network levels different interactions, such as exploration, hierarchy, preference. This review provides broad view how multiple converge medial prefrontal cortex, hippocampus, amygdala regulate behaviors, well potential novel for better control over pathological development.

Language: Английский

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Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder

Open Biology, Journal Year: 2021, Volume and Issue: 11(2)

Published: Feb. 1, 2021

Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to involvement this neuromodulatory in pathophysiology ASD. We investigated whether there disruption eCB ASD pharmacological modulation might offer therapeutic potential. examined three major components system—endogenous cannabinoids, their receptors associated enzymes—in children as well valproic acid (VPA) induced animal model autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, selective inhibitor monoacylglycerol lipase hydrolytic enzyme for 2-AG, examine ASD-like behaviours VPA-induced rats. Results showed that autistic rats exhibited reduced content, degradation enzymes upregulation CBRs. found repetitive stereotypical behaviours, hyperactivity, sociability, social preference cognitive functioning improved after acute chronic JZL184 treatment. efficacy was observed administration dosage regimen 3 mg kg −1 , affected both behaviours. In conclusion, signalling model, boosting 2-AG could ameliorate phenotypes animals. Collectively, results suggested novel approach

Language: Английский

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Systemic enhancement of serotonin signaling reverses social deficits in multiple mouse models for ASD

Neuropsychopharmacology, Journal Year: 2021, Volume and Issue: 46(11), P. 2000 - 2010

Published: July 8, 2021

Language: Английский

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Selective filtering of excitatory inputs to nucleus accumbens by dopamine and serotonin

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(24)

Published: June 8, 2021

Significance Dopamine (DA) and serotonin (5-HT) release in the nucleus accumbens (NAc) influence motivated behaviors, yet mechanisms by which they modulate NAc activity are unclear. Here, we report that DA selectively reduced excitatory postsynaptic currents (EPSCs) from paraventricular thalamus (PVT) inputs, whereas 5-HT EPSCs PVT, ventral hippocampus (vHip), basolateral amygdala (BLA) inputs but not medial prefrontal cortex (mPFC) inputs. Mimicking input-specific effect of via optogenetic inhibition PVT promoted cocaine-conditioned place preference, while mPFC blocked enhancement sociability induced (±)3,4-methylenedioxymethamphetamine (MDMA). Together, these results suggest effects on transmission contribute to distinct modulation behavior is generated 5-HT.

Language: Английский

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Midbrain dopamine neurons arbiter OCD-like behavior

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(46)

Published: Nov. 7, 2022

The neurobiological understanding of obsessive–compulsive disorder (OCD) includes dysregulated frontostriatal circuitry and altered monoamine transmission. Repetitive stereotyped behavior (e.g., grooming), a featured symptom in OCD, has been proposed to be associated with perturbed dopamine (DA) signaling. However, the precise brain circuits participating DA’s control over this behavioral phenotype remain elusive. Here, we identified that DA neurons substantia nigra pars compacta (SNc) orchestrate ventromedial striatum (VMS) microcircuits as well lateral orbitofrontal cortex (lOFC) during self-grooming behavior. SNc–VMS SNc–lOFC dopaminergic projections modulate grooming behaviors striatal microcircuit function differentially. Specifically, activity pathway promotes via D1 receptors, whereas suppresses D2 receptors. SNc neuron thus controls OCD-like both cortical dual gating. These results support pharmacological brain-stimulation treatments for OCD.

Language: Английский

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Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum of Shank3 mutant mice

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: March 16, 2023

Autism is characterized by atypical social communication and stereotyped behaviors. Mutations in the gene encoding synaptic scaffolding protein SHANK3 are detected 1–2% of patients with autism intellectual disability, but mechanisms underpinning symptoms remain largely unknown. Here, we behavior Shank3 Δ11/Δ11 mice from 3 to 12 months age. We observed decreased locomotor activity, increased self-grooming modification socio-sexual interaction compared wild-type littermates. then used RNAseq on four brain regions same animals identify differentially expressed genes (DEGs). DEGs were identified mainly striatum associated transmission (e.g., Grm2, Dlgap1 ), G-protein-signaling pathways Gnal , Prkcg1 Camk2g as well excitation/inhibition balance Gad2 ). Downregulated upregulated enriched clusters medium-sized spiny neurons expressing dopamine 1 (D1-MSN) 2 receptor (D2-MSN), respectively. Several ( Cnr1 Drd4 ) reported striosome markers. By studying distribution glutamate decarboxylase GAD65, encoded showed that compartment was enlarged displayed much higher expression GAD65 mice. Altogether, these results indicate altered -deficient strongly suggest, for first time, excessive related an imbalance striatal matrix compartments.

Language: Английский

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