Substantia nigra

Parkinson's disease has been characterized by the significant role that alpha-synuclein and immune activation play in driving disease progression. Moreover, the immunogenicity of alpha-synuclein-derived epitopes in driving both innate and adaptive immunity has been discovered in prodromal Parkinson's disease. Despite these findings, the mechanistic role of the immune system in contributing to disease ontogenesis remains unknown. Recent evidence has identified alpha-synuclein as a candidate biomarker, with seed amplification assays yielding high sensitivity for sporadic cases of the disease. Pe

…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

…microglia-neuron interactions in the Substantia Nigra (SN) when compared with control individuals, indicating a polarization of microglia in this pathological scenario. Besides, MPTP-treated parkinsonian mice also revealed a significant number of polarized microglia to

…subpopulations, projecting to the substantia nigra and hippocam

…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 (

PACAP is a neuroprotective peptide in Parkinson’s disease models. Earlier we compared the substantia nigra of PACAP knockout (KO) and wild type mice (WT) of different ages and did not find significant 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

Parkinson's disease (PD), as the most prevalent neurodegenerative motor disorder, presents a complex spectrum of symptoms encompassing both motor impairments (bradykinesia, resting tremor, freezing of gait) and non-motor manifestations (depression, anosmia, anxiety). Robust animal models that faithfully replicate this multifaceted pathology are indispensable for comprehensive PD research. This study aims to investigate if depressive-like behaviour, prominent in up to 40% of PD patients (Laux, 2022), emerges in the bilateral human mutated alpha-synuclein (A53T) rat model of PD.40 adult Sprague-

Dopamine (DA) dysregulation has been linked to schizophrenia (SCZ) psychopathology for decades, but there is still an unmet need to identify underlying neural mechanisms. In particular, dopaminergic hyperactivity found in SCZ patients primarily in the associated/dorsomedial striatum (DMS), but not ventral striatum raises the necessity to address the role of the nigrostriatal pathways in SCZ. In order to study DA dysregulation relevant to human disease, we made use of the Df(16)A+/- mouse model of the 22q11.2 Deletion Syndrome, the most common chromosomal microdeletion and the highest genetic r

Dopamine (DA) neurons in the substantia nigra are vital for the control of movement. This fundamental function is encoded by the output signal of DA neurons which switches from spontaneous firing to bursts of action potentials. The latter produces an increase of DA release in targeted areas which is associated to locomotion initiation. The impairment of this process, such as DA neurons degeneration, leads to the motor symptoms of Parkinson’s disease. The activation of the N-methyl-D-aspartate receptors (NMDARs), by the simultaneous binding of glutamate and a co-agonist, is indispensable for th

…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

Dysregulation of serotonin (5-HT) transmission has been implicated as a factor in the development of depression. This study determined the effects of Tat on serotonin transporter (SERT), dynamic 5-HT release, and the effect of induction of Tat expression on mobility in the tail-suspension test (TST) in inducible Tat transgenic (iTat-tg) mice. Optimization of recombinant Tat1-86 (rTat1-86) concentration revealed a Ki of 7.2 nM for it inhibiting 5-HT uptake into mouse synaptosomes. SRI-32743 displayed a partial antagonism with 13 nM affinity and 69.5% Emax for inhibiting 5-HT uptake in CHO cells

…Elevated IL-13 levels within the substantia nigra (SN) during chronic stress, coupled 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

…anisotropy metric across three Substantia Nigra (SN) subregions. The results indicated notable differences in depressed mood percentages

…in dopaminergic neurons in the rat substantia nigra in vivo, and in SH-SY5Y cells in vitro. To investigate the nuclear HDAC5 complex induced by aSyn, we used a co-immunoprecipitation proteomics approach t

…to the ventral tegmental area/substantia nigra

Tumbling is a fancy breed phenotype in domestic pigeons maintained by selective breeding, and it may take different in different sub-breeds. Roughly, it can be defined as the backward somersaults where the pigeon rotates around its neck-to-tail axis during flight. During development following flight onset, they spontaneously start manifesting tumbling, and over time, the tumbling phenotype gets consolidated in such a way that functional losses can emerge such as loss of flight. With its spontaneous early developmental appearance, and pronounced nature with aging, we proposed a corollary betwee

…of dopaminergic neurons in the substantia nigra. The gut microbiota is now recognized as a potential participant in the pathogenesis of PD. This study aims to investigate the effects of Lactobacillus sakei (Ls) on the gut-brain axis and explore the underlying molecular mechanism using a PD model. Probiotics were orally administered for four weeks after MPTP injection. The study observed that Ls significantly improved movement, includi

…thus undergoing neuron loss like the substantia nigra (SN) which is a defining feature of PD that is thought to underlie observed motor symptoms. Interestingly, the LH has strong anatomical projections to the SN, but the behavioural functions associated with this projection have not been determined. We have recently shown that the LH is involved in habitual instrumental responding and spontaneous locomotor activity in

The striatum constitutes the main input structure of the basal ganglia and is mainly composed of GABAergic medium spiny neurons (MSNs) giving rise to the direct and indirect pathways. An additional compartmentalization of the striatum, consisting in the striosomes and the matrix was described decades ago. The respective network organization and functions of these compartments are much less understood along with the differences in their MSNs intrinsic properties. Our aim is to assess the intrinsic properties of the striosomal and matrix neurons and to characterize their functional connectivity.

…the ventral tegmental area (VTA) and substantia nigra (SN) are also involved in regulating defensive behaviors. More recently, the zona incerta (ZI), an overlooked midbrain downstream and functionally mysterious inhibitory nucleus, has been reported to play a role in modulating defensive behaviors. Despite that the ventral midbrain sends projection to the ZI, the neurochemical phenotypes of cells involved in the connection remain poorly understood.Thus we employed retrograde and anterograde tracing app

…loss of dopaminergic neurons in the substantia nigra. Neuronal cells, once impaired, do not undergo spontaneous regeneration; consequently, the disease persists beyond the onset of symptoms. There is a growing recognition of the need for treatments that could protect neurons and potentially modify the disease course because current PD treatments primarily address symptoms without halting the disease progression. Autophagy, a cellular process clearing damaged organelles and proteins, has emerged as a poten

…characterized by a progressive loss of substantia nigra dopaminergic neurons, leading to dopaminergic deafferentation of the striatum and invalidating motor symptoms. Several studies suggest that doxycycline (DOX), an old antibiotic from the tetracycline family, could be a neuroprotective drug candidate for PD (Bortolanza et al, J Neural Transm, 2018). Its antibiotic activity may, however, preclude chronic use in patients. Therefore, we have developed a non-antibiotic derivative of DOX referred to as DDOX (12a-deoxy-dedimethylamino-DOX),

…loss of dopaminergic neurons in the Substantia Nigra and Lewy body formation, resulting in a progressive neurodegenerative disorder with movement defects. The impairment of dopaminergic innervation in PD hinders the two main projection systems from the dorsal striatum (Putamen, Pu, and Caudate Nucleus, CN) from effectively responding to cortical and thalamic signals.A potential role of Oligodendrocytes (OLs) in PD was pointed out by recent works describing GWAS PD variants associated with OLs (Bryois et al, Nat Genet, 2020), PD genes e

Parkinson's disease (PD) is a complex pathology presenting with motor symptoms coupled with a variety of non-motor symptoms originating in the central nervous system or the periphery, resulting in a complex multisystem disease. The development of therapeutic approaches to slow or stop disease progression remains the greatest unmet therapeutic need for PD. The immune system plays a pivotal role in the central and peripheral pathology of PD, reacting to misfolded α‐synuclein with neuroinflammation and dysregulation of peripheral immune responses. Here, we tested the neuroprotective properties of