Dopaminergic neurons

…disease (PD), the brain loses dopaminergic neurons in the substantia nigra compacta (SNc). Highly involved in the basal ganglia-cortex-thalamus-cerebellum (BG-Ctx-T-Cb) network, the main role of dopamine (DA) is in learning, decision-making and motor control, as manifested in the PD symptoms such as rigidity, slowness of movements, tremor and poor behavioural flexibility. Following DA loss, the un

Dopamine plays a crucial role in the neural mechanisms underlying behavior, yet quantifying its impact through genetic modifications presents significant challenges, particularly due to the high-dimensional nature of the resulting data. In this study, we address these challenges by proposing a novel methodological framework using the Random Forest algorithm, tailored for robust multivariate analysis without the typical assumptions required in conventional statistical testing. Our experimental approach involved detailed video recordings of Drosophila melanogaster larvae, focusing on the effects

…loss of Substantia Nigra pars compacta dopaminergic neurons. One cause of the disease is associated with the spreading of α-synuclein aggregates. Recent findings indicate that extracellular α-synuclein oligomers represent the most neurotoxic species and reduce the firing discharge of midbrain neurons, impair network synchronization, up-regulate Cav2.2 Ca channels and neurotransmitter release in cortical neurons. Here we combined conventional electrophysiology (current-clamp) and diamond multi

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra, and it has been reported that α-synuclein accumulates in the gut and then affects the brain along the gut-brain axis. In this study, we used Enterococcus faecium (EF), which was probiotics, that confer health benefits on the host when administered in adequate amounts. C57BL/6 mice, a model of PD induced by MPTP, were treated with EF (1ⅹ1012 CFU/mL). The study showed that motor dysfunction in MPTP-induced PD model mice improved. Additionally, EF was found to decrease the accumulation o

Parkinson’s disease (PD) represents one of the most frequent neurodegenerative disorders for which genetic diagnosis is still challenging. We have recently reported the identification of rare new gene variants in PD patients that support polygenic contribution to the disease. Here we report the identification of novel PD genes and a novel protocol for predictive analysis of PD risk.The study includes the whole exome data of 22 PD families, 804 unrelated PD and 282 healthy subjects.Family-based approach identified rare and disrupting variants, in 44 candidate genes, co-inherited by affected rel

…is mainly characterised by the loss of dopaminergic neurons in the substantia nigra as well as the presence of aggregates called Lewy bodies which consist mostly of alpha-synuclein. Astrocytes and microglia are increasingly being regarded as key players in PD-associated neurodegeneration, and these become ‘activated’ during neuroinflammation. Autophagy and its dysfunction have been implicated in some genetic forms of PD, with alpha-synuclein accumulation and aggregation linked to autophagy suppression. Using alpha-synuclein triplica

Parkinson’s disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) pars compacta, leading to motor and cognitive impairments. The lack of a cure for this disease highlights the urgency in finding drugs that can modify its course. This emphasizes the importance of creating preclinical models that mimic major aspects of the disease. Rotenone, a natural pesticide that inhibits the mitochondrial complex I, has been shown to induce inflammation and selectively destroys nigrostriatal dopaminergic cells and thus presents itself as a

Parkinson’s Disease (PD) is a neurodegenerative disorder associated with the loss of dopaminergic neurons in the nigrostriatal circuit, and the development of motor and non-motor symptoms. Currently, no disease-modifying pharmacological treatments are available, and dopamine-based therapies help to mitigate symptoms but also cause side-effects. In this context, indirect evidence has suggested that activation of metabotropic Glutamate Receptor 3 (mGluR3) exerts neuroprotective effects in animal models of PD. However, the lack of selective agonists/ligands for this receptor has hindered more in-

…In the fruit fly brain, dopaminergic neurons in the mushroom body, a central structure for learning and memory, have been suggested to compute such

…neurodegenerative conditions affecting dopaminergic neurons, such as Parkinson's disease (PD). To investigate the impact of cocaine on cell viability and morphology, dopaminergic neurons from the substantia nigra (SN4741) were cultured. Analysis involved assessing cell death (LDH levels) and cell morphology (GIEMSA staining) after a 24-hour treatment period. Additionally, the effects on reactive oxygen species (ROS) generation (

…changes in the cell number of dopaminergic neurons, but in ageing PACAP KO mice we detected higher number of resting microglia. Our aim was to examine the ventral tegmental area (VTA), which has important function in the regulation of social behavior.We examined the VTA of WT [n=5-5-5] and PACAP KO mice [n=5-4-5] aged 1.5,4, and 8 months. We used triple labelling, dopaminergic neurons were staine

…This damage is associated with losing neurons, including nigral dopaminergic and cholinergic neurons in the Pedunculopontine Nucleus (PPN). Unlike dopaminergic neurons, PPN cholinergic neurons tend to maintain wild-type mtDNA levels by increasing mtDNA copy number (mtCN) in response to mtDNA deletions.Our study isolated single cholinergic neurons from post-mortem PPN tissue of PD patients and controls, examining mtDNA deletions' loc

…by early dysfunction and death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Harnessing this mutation to create an early-onset Parkinson’s disease (PD) mouse model would provide a unique opportunity to clarify the mechanisms involved in the neurodegenerative process and lay the groundwork for the development of neuroprotective strategies. By using CRISPR/Cas9 technology, we created

…probabilistic decision making, and how dopaminergic system might serve to implement this measure. Here we suggest a new approach to find this preference measure and show how it can be computed within a population of dopami

…that can readily differentiate into dopaminergic neurons. Additionally, we aim to analyze in greater detail intracellular changes and differences in extracellular signaling induced by a-Syn in a dosage-dependent manner.We created novel neuronal cell models of PD in ReNVM cells background, stably overexpressing GFP-tagged a-Syn either wild type (WT) or its A53T mutant via lentivirus transduction. Cell

Accumulating evidence shows that dopaminergic neurons of the ventral tegmental area (VTA) are crucial for rewarding and aversive responses. The activity of these neurons is intricately regulated by various neuropeptides, one of which is the endogenous opioid dynorphin. It is thought that the main source of dynorphin in the VTA arises from nucleus accumbens (NAc) D1-MSNs, and that dynorphin acts primarily on kappa opioid receptors (KORs), serving as negative feedback mechanism to modulate dopamine release. Thus, dynorphin signals may regulate dopamine dynamics and, in this way, contribute for r

Dopaminergic neurons (DNs) from the Ventral Tegmental Area (VTA) are associated with addiction and are the first neurons to respond to a single dose of cocaine, leading to long-term potentiation. Gene expression and synaptic activity are reported to recover within the first 24 hours post cocaine exposure, but a memory of the first insult is thought to prevail, as a second exposure leads to more expansive activation. To gain mechanistic insights into the chromatin structure alterations seen by 24h and understand the cascade of events that disturbs networks of regulatory sequences and genes, we

…characterized by the degeneration of dopaminergic neurons in the SNpc, resulting in both motor and non-motor symptoms. Current treatments are limited, and PD's molecular basis involves alpha-synuclein aggregation, ubiquitination dysregulation, and oxidative stress. Nicotine, found in tobacco, has been associated with reduced PD risk in epidemiological studies and shown neuroprotective effects in animal models. However, its impact on oxidative stress remains unclear. A study in

…characterized by the degeneration of dopaminergic neurons of the Substantia Nigra and the accumulation of protein aggregates, called Lewy bodies, where the most abundant protein is alpha-synuclein (a-SYN). In addition to the neurodegeneration and the accumulation of proteins, PD is characterized by chronic low-grade inflammation and mitochondrial alterations that lead to oxidative stress. Currently, the only treatment for PD patients is dopamine replacement therapy (levodopa), which has serious side effects and does

…by the progressive loss of dopaminergic neurons, predominantly within the substantia nigra pars compacta (SNc) region. Dysregulation of FoxO1 has been implicated in various neurodegenerative diseases, including Alzheimer's disease and PD, yet the precise underlying mechanisms remain largely elusive. In this study, we investigated the impact of α-synuclein pre-formed fibrils (PFF) treatment on BV-2 microglial cells to elucidate alterations in molecular properties and neuronal degeneration. Surprisingly, our find

…Substantia Nigra pars compacta (SNpc) dopaminergic neurons, eventually causing cell death. Interestingly, defective activity or mutations in GBA1, the gene encoding the lysosomal enzyme Glucocerebrosidase (GCase), are the strongest risk factor to develop PD. Based on this evidence, reverting the cytological and molecular abnormalities caused by GCase mutations or enhancing the activity of the wild type enzyme may represent a feasible therapeut

…protein is involved in the loss of dopaminergic neurons in PD. In this project, we aim to illuminate the influence of hypoxia on the progression and initiation of PD in a murine model with focus on inflammation. Activity and differentiation of immune cells i

The degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is a hallmark of Parkinson’s disease (PD). Nevertheless, little is known about the molecular signals that are altered in the prodromal phase in the adult striatum. To address this, we have used spatial transcriptomics and single-nucleus RNA sequencing to characterize the molecular events in mouse models of prodromal PD. We have used two different PD models: a) a progressive dopamine degeneration model of mitochondrial dysfunction (MitoPark mice), and b) a mild toxin model based on a low-dose unilateral 6-hydr

…with the expression of IL-13Rα1 in dopaminergic neurons, suggest their potential involvement in neurodegenerative processes. However, the role of IL-13Rα1 in the pathological state of PD remains unclear. We investigated IL-13Rα1 expression patterns in postmortem brain tissues from PD patients and age-matched controls using western blo