Topic: tyrosine hydroxylase

Parkinson’s disease (PD) results in midbrain dopaminergic neuron degeneration and neuronal accumulation of alpha-synuclein (a-syn). The ‘brain-first vs body-first’ hypothesis of PD proposes that a-syn pathology begins in the brain then spreads to the gut, or conversely begins in the gut then spreads to the brain, via the peripheral nervous system. The gut microbiota has been implicated in PD, and early dysbiosis and a-syn accumulation in the gut have been reported in ‘body-first’ PD. However, it is unclear if these events also occur in ‘brain-first’ PD. Here we investigated whether alterations

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) 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

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

Electroconvulsive therapy (ECT) is a well-established treatment for psychiatric disorders. Recent reports show that ECT improves motor deficits in Parkinson's disease (PD), while the mechanism of action remains unclear. To investigate the effects of ECT in PD, we produced partial dopaminergic depletion by unilateral striatal injection of 6-OHDA. After three weeks, behavioral testing was performed using the open field and corridor test. Animals with a lateralized phenotype were randomized into ECT or sham treatment. After a two-week treatment interval with daily ECT, behavioral testing was repe

The nidopallium caudolaterale (NCL) of the avian brain is a functional analogue of the mammalian prefrontal cortex. It plays a central role in different types of associative learning, including conditioning and extinction learning. The NCL receives a dense innervation of tyrosine hydroxylase (TH) immunopositive fibers, which form characteristic basket formations around their target somata. This distinctive innervation profile enabled the identification of the NCL in pigeons, chickens, zebra finches, crows and blackcaps. In this study, we characterized the catecholaminergic system of the Japane

Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by dopaminergic neuronal damage. We evaluated the neuroprotective effect of γ-amino butyric acid (GABA) in PD and the underlying mechanism focusing on WNT/β-catenin signaling mediated by the MAPK pathway. We treated MPTP-induced SH-SY5Y cells with GABA Low and High concentrations, and we also treated PD model mice with GABA. GABA treatment effectively reduced the expression of biomarkers associated with PD, particularly lewy’s bodies and α-synuclein, and increased the number of tyrosine hydroxylase positive cells. G

Parkinson’s disease (PD) affects more than 6 million people worldwide, and will affect more in coming decades. There are no drugs available for PD that alter progression of disease. Current symptomatic treatments provide limited relief and have side effects. Enhanced GABAergic neurotransmission contributes to Parkinson’s disease (PD) pathogenesis and to some motor and non-motor symptoms. In animal models, GABA levels are increased in substantia nigra pars compacta, leading to reduced expression of tyrosine hydroxylase (TH) in neurons which contributes to the behavioural deficits. The aim was t

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons, leading to a spectrum of motor and non-motor symptoms. While motor deficits serve as the primary criteria for diagnosis, emerging evidence suggests that non-motor symptoms may also significantly contribute to the disease's progression. In this study, our aim was to investigate the potential impact of IGF-1 on the progression of emotional-like behavioral deficits in a rat model of neurotoxicity induced by 6-OHDA infusion into the dorsolateral striatum. We evaluated behavioral chang

Olfaction is a crucial sense for many species, influencing behavioral responses like mating and reproduction. A significant dopaminergic (DA) population is found in the mouse main olfactory bulb (OB), with inhibitory interneurons identified by tyrosine hydroxylase (TH) expression and divided into two major groups (i.e., small and large cells) according to their shape, generation time, and biophysical characteristics. Although it is known that salient stimuli activate midbrain DA neurons, it is unclear if OB DA cells are involved in processing ethologically relevant odorants, especially those a

Tyrosine hydroxylase (TH) expressing neurons in the arcuate nucleus of hypothalamus (ARC), has a central role in regulating appetite and metabolism. It has been shown that activity changes in these neurons are necessary and sufficient to acutely regulate feeding behavior. TH neurons send dense intrahypothalamic axonal projections and make synaptic connections to paraventricular nucleus (PVN), which have been shown to be the key downstream target region. Since the ARCTH→PVN synaptic connection plays a crucial role in feeding, possible changes in the strength of this connection are also likely t

Human brain organoids are 3D self-assembling constructs obtained from human pluripotent stem cells, differentiating, and recapitulating the structural and functional complexity of the human brain. Quantitatively describing the cellular spatial arrangement within these constructs and their morphology is important to assess their structural resemblance to the human brain, and thus effectively demonstrating their ability to recapitulate the brain salient microstructural features. Thanks to pluripotent stem cell technology, brain organoids obtained from cells of healthy and diseased patients will

Neuronal circuits located in the midbrain play a critical role in controlling defensive behavior. However, it is still elusive how different neuron types contribute to distinct behavioral outcomes during the presence of threat. In this study, we investigated neurons expressing vasoactive intestinal polypeptide (VIP) in the ventral periaqueductal gray (PAG) and dorsal raphe nucleus in mice. These VIP-expressing neurons also expressed tyrosine hydroxylase (TH), a marker for dopaminergic cells. Using viral tracing conducted in Vip-Cre mice, we observed that these VIP-expressing neurons innervated

Dysfunctional dopaminergic neurotransmission is implicated in several pathologies, including movement disorders such as parkinsonism and psychiatric diseases, suggesting overlapping pathological mechanisms. The dopamine transporter (DAT) is a key regulator of dopamine signalling and rare disease-associated DAT variants can cause psychiatric diseases and early-onset parkinsonism. However, the pathobiological processes that link DAT dysfunction to both parkinsonism and psychiatric symptoms are unknown. To investigate this, we developed a novel mouse disease model that expresses two mutations in

Parkinson's disease (PD) is a neurodegenerative disorder 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),

Dopaminergic neuron functions rely on active synaptic vesicle dynamics and proteostasis. Deficientendocytosis due to lack of endophilins-A, key endocytic adaptors, alters the expression of genesassociated with ataxia, Parkinson's disease and protein homeostasis. Fbxo32, a E3-ubiquitin ligaserequired for muscle atrophy but also expressed in the brain, was shown to be up-regulated inendophilin mutants. Hence, we aimed to investigate the dopaminergic system alterations in theendophilins-A murine model, and explore the effects of Fbxo32 genetic modifications on dopaminedegeneration in this mammali

Endoplasmic reticulum-mitochondrial contact sites (ERMCS) play an important role in lipid metabolism, calcium signaling, and autophagy. Disruption of the ERMCS has been reported to be linked to several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). However, the etiological role of ERMCS in these diseases remains unclear. We have previously established tyrosine hydroxylase reporter (TH-GFP) iPSC lines from a PD patient with a PRKN mutation for correlative light-electron microscopy (CLEM) analysis and live cell i

Sensory systems deploy diverse strategies for discriminating similar stimuli. For instance, spatially isotropic lateral inhibition between neurons showing overlapping receptive fields allows contrast enhancement of primary stimulus representations in the visual system. In the olfactory bulb (OB), odorant identity is primarily represented as a spatially discontinuous map of activated glomeruli. Prior observations on mixture inhibition across glomeruli led us to hypothesize that so-called superficial short-axon-cells -a sub-population of GABAergic/dopaminergic juxtaglomerular cells- underlie a t

Compelling evidence supports that exploiting both patient-derived and animal models is pivotal to reach a better understanding of Parkinson’s disease (PD) (DOI:10.1002/mds.28387). However, working with in vivo models can be challenging as most of them only partially reproduce the pathology at advanced age.We recently developed a novel zebrafish transgenic (tg) line expressing human full-length alpha-synuclein (aSyn) with an N-terminal mCherry tag named Tg(elavl3:mCherry-hsa.SNCA) which exhibit a series of PD-like features already in the larval stage. At 5 days-post-fertilization (dpf), Tg(elav