The voiding efficiency in rat models with dopaminergic brain lesions induced through unilateral and bilateral intrastriatal injections

Bladder dysfunction is a common phenomenon in Parkinson’s disease (PD) patients. A research attempt was made to analyze the voiding efficiency (VE) and bladder functions in rats with PD induced by unilateral or bilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. PD rats were divided into unilateral- and bilateral-injected groups and subjected to rotation and beam walking tests. Further, the experimental rats underwent cystometric measurements for analyses of bladder dysfunction and VE. Immunohistochemical analysis was performed to analyze the dopaminergic neuron depletion on the target area. Outcomes of the rotation and beam walking tests revealed the extent of parkinsonism in the experimental rats. Urodynamic observations denoted that rats with unilateral PD exhibited a significantly decreased VE (from 68.3±3.5% to 32.7±5.8%), while rats with bilateral PD displayed a much-reduced and substantially lower level of VE of 18.3±5.1% compared to the control value and to that of rats with unilateral PD. Rats with bilateral PD showed more-extensive behavioral deficits and urodynamic changes than did rats with unilateral PD. These significant changes in motor, behavioral, bladder function and VE were due to an extensive degeneration of dopaminergic neurons in the substantia nigra region on both sides of the brain. The obtained results were substantiated with appropriate immunohistochemical results.

Download Full-text

Apomorphine-induced operant deficits: a neuroleptic-sensitive but drug- and dose-dependent animal model of behavior

Psychiatry and Psychobiology ◽

10.1017/s0767399x00000894 ◽

1987 ◽

Vol 2 (4) ◽

pp. 266-273

Author(s):

P. Carnoy ◽

S. Ravard ◽

D. Hervé ◽

J.-P. Tassin ◽

P. Soubrié

Keyword(s):

Cognitive Processes ◽

Dopaminergic Neurons ◽

Operant Behavior ◽

Fixed Ratio ◽

Food Delivery ◽

Behavioral Deficits ◽

Dopaminergic Transmission ◽

Dopaminergic Systems ◽

6 Hydroxydopamine ◽

Dose Dependent

SummaryIn order to further assess the alterations which might underly behavioral deficits associated with a reduced dopaminergic transmission, the effects of apomorphine at doses thought to stimulate dopaminergic autoreceptors were studied on rat operant behavior.Low doses of apomorphine caused a reward deficit when animais were shifted from continuons reinforcement to fixed ratio schedules of food delivery (fig. 1). This effect could be accounted for by a decreased ability of secondary reinforcers to sustain responding and/or by a disruption of cognitive processes (Table 1). The apomorphine-induced reward deficit in the fixed ratio 4 schedule was reversed by “disinhibitory” neuroleptics including amisulpride, pimozide, pipotiazine and sulpiride, at low to moderate doses. Conversely, “conventional” neuroleptics such as chlorpromazine, fluphenazine, haloperidol, metoclopramide and thioridazine were found inactive in reversing the deficit caused by apomorphine (fig. 2). Results obtained after lesion of dopaminergic neurons by 6-hydroxydopamine suggested that the behavioral deficit induced by apomorphine was related not so much to a reduction in dopaminergic activity in given restricted areas such as the VTA (fig. 3), the nucleus accumbens (fig. 4) or the prefrontal cortex (fig. 5), as to a functional imbalance between mesolimbic and mesocortical dopaminergic systems.

Download Full-text

Prefeeding release of paraventricular neuropeptide Y is mediated by ascending noradrenergic neurons in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.4.e596 ◽

1996 ◽

Vol 270 (4) ◽

pp. E596-E600 ◽

Cited By ~ 1

Author(s):

T. Yoshihara ◽

S. Honma ◽

K. Honma

Keyword(s):

Food Intake ◽

Neuropeptide Y ◽

Paraventricular Nucleus ◽

The Other ◽

Neuronal System ◽

Noradrenergic Neurons ◽

Norepinephrine Level ◽

Control Value ◽

6 Hydroxydopamine ◽

The Brain

The neuronal system responsible for the release of neuropeptide Y (NPY) in the paraventricular nucleus (PVN) was examined in rats under food deprivation and restricted daily feeding (RF). The ascending noradrenergic bundle (NAB) of neurons from the brain stem were destructed by microinjection of 6-hydroxydopamine (6-OHDA), and the extracellular NPY level in the PVN was measured by push-pull perfusion. 6-OHDA significantly reduced the extracellular norepinephrine level in the PVN to 15% of the control value when injected into the PVN and to 40% when injected into the midbrain ventral NAB. 6-OHDA administration into the NAB affected neither the deprivation-induced increase nor the feeding-induced decrease in the extracellular NPY. The amount of food intake after refeeding was not changed by the 6-OHDA treatment. On the other hand, 6-OHDA injection into the PVN or NAB not only decreased the extracellular NPY level, the amount of food intake was not change by the 6-OHDA treatment. It is concluded that the NAB is involved in the prefeeding NPY release in rats under RF but not in the deprivation-induced NPY release.

Download Full-text

502: Cerebral Control of Bladder Function: The Brain-Bladder Connection

The Journal of Urology ◽

10.1016/s0022-5347(18)37764-4 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 134-134 ◽

Cited By ~ 1

Author(s):

Derek J. Griffiths ◽

Stuart Derbyshire ◽

Elizabeth Logue ◽

V. Andrew Stenger ◽

Neil M. Resnick

Keyword(s):

Bladder Function ◽

Cerebral Control ◽

The Brain

Download Full-text

Comparison of Cytocidal Activities of L-DOPA and Dopamine in S. cerevisiae and C. glabrata

Current Bioactive Compounds ◽

10.2174/1573407214666180108144216 ◽

2020 ◽

Vol 16 (1) ◽

pp. 90-93

Author(s):

Carmen E. Iriarte ◽

Ian G. Macreadie

Keyword(s):

Saccharomyces Cerevisiae ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Candida Glabrata ◽

High Sensitivity ◽

Time Dependent ◽

Colony Forming Units ◽

Dependent Cell ◽

The Brain

Background: Parkinson's Disease results from a loss of dopaminergic neurons, and reduced levels of the neurotransmitter dopamine. Parkinson's Disease treatments involve increasing dopamine levels through administration of L-DOPA, which can cross the blood brain barrier and be converted to dopamine in the brain. The toxicity of dopamine has previously studied but there has been little study of L-DOPA toxicity. Methods: We have compared the toxicity of dopamine and L-DOPA in the yeasts, Saccharomyces cerevisiae and Candida glabrata by cell viability assays, measuring colony forming units. Results: L-DOPA and dopamine caused time-dependent cell killing in Candida glabrata while only dopamine caused such effects in Saccharomyces cerevisiae. The toxicity of L-DOPA is much lower than dopamine. Conclusion: Candida glabrata exhibits high sensitivity to L-DOPA and may have advantages for studying the cytotoxicity of L-DOPA.

Download Full-text

Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms22031059 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1059

Author(s):

Bodo C. Melnik

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Dopaminergic Neurons ◽

Vagal Nerve ◽

Β Cells ◽

Pancreatic Β Cells ◽

The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

Download Full-text

Importance of Nanoparticles for the Delivery of Antiparkinsonian Drugs

Pharmaceutics ◽

10.3390/pharmaceutics13040508 ◽

2021 ◽

Vol 13 (4) ◽

pp. 508

Author(s):

Sara Silva ◽

António J. Almeida ◽

Nuno Vale

Keyword(s):

Side Effects ◽

Dopaminergic Neurons ◽

Lewy Bodies ◽

Pharmacokinetic Profile ◽

The Elderly ◽

Motor Symptoms ◽

Administration Routes ◽

Pharmaceutical Therapy ◽

Drug Pharmacokinetic ◽

The Brain

Parkinson’s disease (PD) affects around ten million people worldwide and is considered the second most prevalent neurodegenerative disease after Alzheimer’s disease. In addition, there is a higher risk incidence in the elderly population. The main PD hallmarks include the loss of dopaminergic neurons and the development of Lewy bodies. Unfortunately, motor symptoms only start to appear when around 50–70% of dopaminergic neurons have already been lost. This particularly poses a huge challenge for early diagnosis and therapeutic effectiveness. Actually, pharmaceutical therapy is able to relief motor symptoms, but as the disease progresses motor complications and severe side-effects start to appear. In this review, we explore the research conducted so far in order to repurpose drugs for PD with the use of nanodelivery systems, alternative administration routes, and nanotheranostics. Overall, studies have demonstrated great potential for these nanosystems to target the brain, improve drug pharmacokinetic profile, and decrease side-effects.

Download Full-text