dopaminergic neurons

Parkinson's disease (PD) is a complex neurodegenerative disorder without a cure. The onset of PD symptoms corresponds to 50% loss of midbrain dopaminergic (mDA) neurons, limiting early-stage understanding of PD. To shed light on early PD development, we study time series scRNA-seq datasets of mDA neurons obtained from patient-derived induced pluripotent stem cell differentiation. We develop a new data integration method based on Non-negative Matrix Tri-Factorization that integrates these datasets with molecular interaction networks, producing condition-specific "gene embeddings"...

Parkinson's disease (PD) poses a significant challenge in neurodegenerative disorders, characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). The intricate mechanisms orchestrating DA neurodegeneration in PD are not fully understood, necessitating the exploration of innovative therapeutic approaches. Recent studies have implicated ferroptosis as a major contributor to the loss of DA neurons, revealing a complex interplay between iron accumulation and neurodegeneration...

AIMS: Continued alcohol consumption despite negative consequences is a core symptom of alcohol use disorder. This is modeled in mice by pairing negative stimuli with alcohol, such as adulterating alcohol solution with quinine. Mice consuming alcohol under these conditions are considered to be engaging in aversion-resistant intake. Previously, we have observed sex differences in this behavior, with females more readily expressing aversion-resistant consumption. We also identified three brain regions that exhibited sex differences in neuronal activation during quinine-alcohol drinking: ventromedial prefrontal cortex (vmPFC), posterior insular cortex (PIC), and ventral tegmental area (VTA)...

INTRODUCTION: Studies have shown that dexmedetomidine (DEX, an a2-adrenoceptors agonist) provides a neuroprotective effect and influences blood glucose levels. Here, we evaluated the effect of prolonged treatment with low doses of DEX on the survival rate of dopaminergic (DAergic) neurons in the substantia nigra and also serum glucose levels in 6-hydroxydopamine (6-OHDA) - induced Parkinson's disease (PD) in the rat. MATERIAL AND METHODS: The neurotoxin of 6-OHDA was injected into the medial forebrain bundle by stereotaxic surgery...

BACKGROUND: In recent years, dental pulp stromal cells (DPSCs) have emerged as a promising therapeutic approach for Parkinson's disease (PD), owing to their inherent neurogenic potential and the lack of neuroprotective treatments for this condition. However, uncertainties persist regarding the efficacy of these cells in an undifferentiated state versus a neuronally-induced state. This study aims to delineate the distinct therapeutic potential of uninduced and neuronally-induced DPSCs in a rodent model of PD induced by 6-Hydroxydopamine (6-OHDA)...

The objective of the present narrative review was to synthesize existing clinical and epidemiological findings linking manganese (Mn) exposure biomarkers to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), and to discuss key pathophysiological mechanisms of neurodevelopmental disorders that may be affected by this metal. Existing epidemiological data demonstrated both direct and inverse association between Mn body burden and ASD, or lack of any relationship. In contrast, the majority of studies revealed significantly higher Mn levels in subjects with ADHD, as well as direct relationship between Mn body burden with hyperactivity and inattention scores in children, although several studies reported contradictory results...

BACKGROUND: Clinical trials have provided evidence that transplants of dopaminergic precursors, which may be replaced by new in vitro stem cell sources, can integrate into the host tissue, and alleviate motor symptoms in Parkinson´s disease (PD). In some patients, deterioration of graft function occurred several months after observing a graft-derived functional improvement. Rejection of peripheral organs was initially related to HLA-specific antibodies. However, the role of non-HLA antibodies is now considered also relevant for rejection...

Synthetic opioids such as fentanyl contribute to the vast majority of opioid-related overdose deaths, but fentanyl use remains broadly understudied. Like other substances with misuse potential, opioids cause lasting molecular adaptations to brain reward circuits, including neurons in the ventral tegmental area (VTA). The VTA contains numerous cell types that play diverse roles in opioid use and relapse; however, it is unknown how fentanyl experience alters the transcriptional landscape in specific subtypes...

BACKGROUND: Degeneration of the nigrostriatal dopaminergic pathway has been seen as a significant cause of movement disability in Parkinson's disease (PD) patients. However, the exact reason for these degenerative changes has remained obscure. In recent years, incretins have been neuroprotective in various pathologies. In the current study, we have investigated the neuroprotective potential of alogliptin (Alo), a dipeptidyl peptidase-IV (DPP-IV) inhibitor, in a lipopolysaccharide (LPS) induced experimental model of PD...

Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression...

Parkinson's disease (PD), as a neurologically implemented disease with complex etiological factors, has a complex and variable pathogenesis. Accompanying further research, neuroinflammation has been found to be one of the possible factors in its pathogenesis. Microglia, as intrinsic immune cells in the brain, play an important role in maintaining microenvironmental homeostasis in the brain. However, over-activation of neurotoxic microglia in PD promotes neuroinflammation, which further increases dopaminergic (DA) neuronal damage and exacerbates the disease process...

Adenosine A2A receptor (A2A R) antagonists are the leading nondopaminergic therapy to manage Parkinson's disease (PD) since they afford both motor benefits and neuroprotection. PD begins with a synaptic dysfunction and damage in the striatum evolving to an overt neuronal damage of dopaminergic neurons in the substantia nigra. We tested if A2A R antagonists are equally effective in controlling these two degenerative processes. We used a slow intracerebroventricular infusion of the toxin MPP+ in male rats for 15 days, which caused an initial loss of synaptic markers in the striatum within 10 days, followed by a neuronal loss in the substantia nigra within 30 days...

There are currently no disease-modifying therapies for Parkinson's disease (PD), a progressive neurodegenerative disorder associated with dopaminergic neuronal loss. There is increasing evidence that endogenous dopamine (DA) can be a pathological factor in neurodegeneration in PD. Tyrosine hydroxylase (TH) is the key rate-limiting enzyme for DA generation. Drugs that inhibit TH, such as alpha-methyltyrosine (α-MT), have recently been shown to protect against neurodegeneration in various PD models. DA receptor agonists can activate post-synaptic DA receptors to alleviate DA-deficiency-induced PD symptoms...

Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may induce neural tube defects in infants born to women taking the drug during pregnancy. Subsequent reports did not definitively confirm these findings. Recent studies in animal models have highlighted the association between DTG exposure in utero and congenital anomalies, and an increased risk of neurologic abnormalities in children exposed during in utero life has been reported...

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Dopamine (DA) neurons in the substantia nigra pars compacta, which have axonal projections to the dorsal striatum (dSTR), degenerate in PD. In contrast, DA neurons in the ventral tegmental area, with axonal projections to the ventral striatum, including the nucleus accumbens (NAcc) shell, are largely spared. This study aims to uncover the relative contributions of glycolysis and oxidative phosphorylation (OxPhos) to DA release in the striatum...

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Motilin (MLN) is a peptide hormone originally isolated from the mucosa of the porcine intestine. Its orthologs have been identified in various vertebrates. Although MLN regulates gastrointestinal motility in tetrapods from amphibians to mammals, recent studies indicate that MLN is not involved in the regulation of isolated intestinal motility in zebrafish, at least in vitro. To determine the unknown function of MLN in teleosts, we examined the expression of MLN and the MLN receptor (MLNR) at the cellular level in Japanese medaka (Oryzias latipes)...

Aggregative α-synuclein and incurring oxidative stress are pivotal cascading events, leading to dopaminergic (DAergic) neuronal loss and contributing to clinical manifestations of Parkinson's disease (PD). Our previous study demonstrated that 2-butoxytetrahydrofuran (2-BTHF), isolated from Holothuria scabra ( H. scabra ), could inhibit amyloid-β aggregation and its ensuing toxicity, which leads to Alzheimer's disease. In the present study, we found that 2-BTHF also attenuated the aggregative and oxidative activities of α-synuclein and lessened its toxicity in a transgenic Caenorhabditis elegans ( C...

The brown rat (Rattus norvegicus) is known to show three types of behavioral responses to novel objects. Whereas some rats are indifferent to novel objects, neophobic and neophilic rats show avoidance and approach behavior, respectively. Here, we compared the dopaminergic, serotonergic, and noradrenergic systems immunohistochemically among these rats. Trapped wild rats and laboratory rats were first individually exposed to the novel objects in their home cage. Wild rats were divided into neophobic and indifferent rats depending on their behavioral responses...

Neurotoxins have been extensively investigated, particularly in the field of neuroscience. They induce toxic damage, oxidative stress, and inflammation on neurons, triggering neuronal dysfunction and neurodegenerative diseases. Here we demonstrate the neuroprotective effect of a silicon (Si)-based hydrogen-producing agent (Si-based agent) in a juvenile neurotoxic mouse model induced by 6-hydroxydopamine (6-OHDA). The Si-based agent produces hydrogen in bowels and functions as an antioxidant and anti-inflammatory agent...