Past, Present, and Future of the Pathophysiological Model of the Basal Ganglia

The current model of basal ganglia (BG) was introduced two decades ago and has settled most of our current understanding of BG function and dysfunction. Extensive research efforts have been carried out in recent years leading to further refinement and understanding of the normal and diseased BG. Several questions, however, are yet to be resolved. This short review provides a synopsis of the evolution of thought regarding the pathophysiological model of the BG and summarizes the main recent findings and additions to this field of research. We have also tried to identify major challenges that need to be addressed and resolved in the near future. Detailed accounts and state-of-the-art developments concerning research on the BG are provided in the articles that make up this Special Issue

Clinical Features, Pathophysiology, and Treatment of Levodopa-Induced Dyskinesias in Parkinson’s Disease

Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal movement control. In patients with Parkinson's disease, the chronic levodopa treatment induces dyskinetic movements known as levodopa-induced dyskinesias (LID). This paper analyzed the pathophysiology, clinical manifestations, pharmacological treatments, and surgical procedures to treat hyperkinetic disorders. Surgery is currently the only treatment available for Parkinson's disease that may improve both parkinsonian motor syndrome and LID. However, this paper shows the different mechanisms involved are not well understood

Editorial foreword: Angiogenesis: Cells, tissues and organs

On the occasion of his 90th birthday, this Special Issue is dedicated to Professor Robert Auerbach. Born 1929 in Berlin, Germany, he and his family escaped Nazi Germany in 1939 and emigrated to the United States, where he became a zoologist and ultimately Professor and Director of the Developmental Biology Training Program at the Department of Zoology, Madison, University of Wisconsin, USA. In Auerbach's laboratory, students and scientists of many different nations, including politically persecuted ones, harmoniously worked together on different aspects of angiogenesis. One of the hallmarks of Auerbach's career as a scientist was and is his generosity towards others, sharing his equipment and ideas freely, his integrity and his collegiality. His significant contributions to angiogenesis and tumour research include the finding that angiogenesis in tumours can occur even after their irradiation (Auerbach, Arensman, Kubai, & Folkman, 1975) and an explanation of organ selectivity in the spread of metastasizing cancer cells (Auerbach, 1988). Through his outstanding papers on in vitro methods in angiogenesis research, he also supported animal welfare (Alby & Auerbach, 1984; Auerbach, Lewis, Shinners, Kubai, & Akhtar, 2003; Gumkowski, Kaminska, Kaminski, Morrissey, & Auerbach, 1987; Obeso, Weber, & Auerbach, 1990)

A Mg isotopic perspective on the mobility of magnesium during serpentinization and carbonation of the Oman Ophiolite

Author Posting. © American Geophysical Union, 2021. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 126(2), (2021): e2020JB020237, https://doi.org/10.1029/2020JB020237.Alteration of mantle peridotite in the Samail ophiolite forms secondary minerals, mainly serpentine and Mg‐rich carbonates. Magnesium accounts for ∼25 – 30% of peridotite mass and its mobility can be used to trace this alteration. We report the first set of Mg isotope measurements from peridotites and their alteration products in Oman. Partially serpentinized peridotites have Mg isotope ratios that are indistinguishable from estimates for the average mantle and bulk silicate earth (δ26Mg = −0.25 ± 0.04‰). However, more extensively altered peridotite samples show large shifts in Mg isotopic composition. The range of δ26Mg values for our suite of alteration products from the mantle section is ∼4.5‰ (from −3.39‰ to 1.19‰), or >60% of the total range of terrestrial variability in δ26Mg values. Serpentine veins are typically enriched in 26Mg (max δ26Mg value = 0.96‰) whereas Mg‐carbonate veins are associated with low 26Mg/24Mg ratios (magnesite δ26Mg = −3.3‰, dolomite δ26Mg = −1.91‰). Our preferred explanation for the range in δ26Mg values involves coprecipitation of serpentine and carbonates at water‐to‐rock ratios >103. The coincidence of alteration products characterized by δ26Mg values that are both lower and higher than bulk silicate Earth and the finite 14C ages of the carbonates suggest that both serpentinization and carbonation are ongoing in Oman. Rates of calcite precipitation in travertines inferred from Δ26Mgcal‐fl suggest that travertine formation in Oman sequesters a total of 106–107 kg CO2/yr, consistent with previous estimates.This work was supported through the Sloan Foundation–Deep Carbon Observatory (Grant 2014‐3‐01, Kelemen PI), the U.S.‐National Science Foundation (NSF‐EAR‐1516300, Kelemen lead PI).2021-06-0

Effects of Gestational Intermittent Hypoxia on Placental Morphology and Fetal Development in a Murine Model of Sleep Apnea

Obstructive sleep apnea (OSA) during pregnancy is characterized by episodes of intermittent hypoxia (IH) during sleep, resulting in adverse health outcomes for mother and offspring. Despite a prevalence of 8-20% in pregnant women, this disorder is often underdiagnosed.We have developed a murine model of gestational OSA to study IH effects on pregnant mothers, placentas, fetuses, and offspring. One group of pregnant rats was exposed to IH during the last 2 weeks of gestation (GIH). One day before the delivery date, a cesarean section was performed. Other group of pregnant rats was allowed to give birth at term to study offspring's evolution.Preliminary results showed no significant weight differences in mothers and fetuses. However, the weight of GIH male offspring was significantly lower than the controls at 14 days (p < 0.01). The morphological study of the placentas showed an increase in fetal capillary branching, expansion of maternal blood spaces, and number of cells of the external trophectoderm in the tissues from GIH-exposed mothers. Additionally, the placentas from the experimental males were enlarged (p < 0.05). Further studies are needed to follow the long-term evolution of these changes to relate the histological findings of the placentas with functional development of the offspring in adulthood.Ayudas para la realización de proyectos de investigación UVa 2021 (PROYEMER 57-E.O.

Computer-Based Visualization System for the Study of Deep Brain Structures Involved in Parkinson’s Disease

[EN]Parkinson’s Disease is characterized by alterations in deep brain structures and pathways involved in movement control. However, the understanding of neuroanatomy and spatial relationships of deep brain structures remains a chal lenge for medical students. Recent developments in informa tion technology may help provide new instructional material that addresses this problem. This paper aims to develop an interactive and digital tool to enhance the study of the anatom ical and functional neurological basis involved in Parkinson’s Disease. This tool allows the organization and exploration of complex neuroanatomical contents related with Parkinson’s Disease in an attractive and interactive way. Educational im plications of this tool are analyzed

Gradual distance dispersal shapes the genetic structure in an alpine grasshopper

The location of the high mountains of southern Europe has been crucial in the phylogeography of most European species, but how extrinsic (topography of sky islands) and intrinsic features (dispersal dynamics) have interacted to shape the genetic structure in alpine restricted species is still poorly known. Here we investigated the mechanisms explaining the colonisation of Cantabrian sky islands in an endemic flightless grasshopper. We scrutinised the maternal genetic variability and haplotype structure, and we evaluated the fitting of two migration models to understand the extant genetic structure in these populations: Long-distance dispersal (LDD) and gradual distance dispersal (GDD). We found that GDD fits the real data better than the LDD model, with an onset of the expansion matching postglacial expansions after the retreat of the ice sheets. Our findings suggest a scenario with small carrying capacity, migration rates, and population growth rates, being compatible with a slow dispersal process. The gradual expansion process along the Cantabrian sky islands found here seems to be conditioned by the suitability of habitats and the presence of alpine corridors. Our findings shed light on our understanding about how organisms which have adapted to live in alpine habitats with limited dispersal abilities have faced new and suitable environmental conditions.British Ecological Society | Ref. 4278Ministerio de Economía y Competitividad | Ref. CGL2014-53899-PAgencia Estatal de Investigación | Ref. CGL2017-85191-PAgencia Estatal de Investigación | Ref. RYC-2015-18241Gobierno del Principado de Asturias | Ref. IDI/2018/000151Ministerio de Economía y Competitividad | Ref. CGL2011-2817

Universal correlations along the BEC-BCS crossover

We show that the long-distance behavior of the two-body density correlation functions and the Cooper-pair probability density of a balanced mixture of a two-component Fermi gas at $T = 0$, is universal along the BEC-BCS crossover. Our result is demonstrated by numerically solving the mean-field BCS model for different finite short-range atomic interaction potentials. We find an analytic expression for the correlation length in terms of the chemical potential and the energy gap at zero momentum.Comment: 6 pages, 3 figure

Neuron types in the primate striatum: stereological analysis of projection neurons and interneurons in control and parkinsonian monkeys

The striatum is mainly composed of projection neurons. It also contains interneurons, which modulate and control striatal output. The aim of the present study was to assess the percentages of projection neurons and interneuron populations in the striatum of control monkeys and of parkinsonian monkeys. Methods: Unbiased stereology was used to estimate the volume density of every neuron population in the caudate, putamen and ventral striatum of control monkeys and of monkeys treated with MPTP, which results in striatal dopamine depletion. The various neuron population phenotypes were identified by immunohistochemistry. All analyses were performed within the same subjects using similar processing and analysis parameters, thus allowing for reliable data comparisons. Results: In control monkeys, the projection neurons, which express the dopamine-and-cAMP-regulated-phosphoprotein, 32-KDa (DARPP-32), were the most abundant: ~86% of the total neurons counted. The interneurons accounted for the remaining 14%. Among the interneurons, those expressing calretinin were the most abundant (Cr+: ~57%; ~8% of the total striatal neurons counted), followed those expressing Parvalbumin (Pv+: ~18%; 2.6%), dinucleotide phosphate-diaphorase (NADPH+: ~13%; 1.8%), choline acetyltransferase (ChAT+: ~11%; 1.5%) and tyrosine hydroxylase (TH+: ~0.5%; 0.1%). No significant changes in volume densities occurred in any population following dopamine depletion, except for the TH+ interneurons, which increased in parkinsonian non-symptomatic monkeys and even more in symptomatic monkeys. Conclusions: These data are relevant for translational studies targeting specific neuron populations of the striatum. The fact that dopaminergic denervation does not cause neuron loss in any population has potential pathophysiological implication

Early paradoxical increase of dopamine: A neurochemical study of olfactory bulb in asymptomatic and symptomatic MPTP treated monkeys

Parkinson’s disease (PD) is a neurodegenerative disease with both motor and non-motor manifestations. Hyposmia is one of the early non-motor symptoms, which can precede motor symptoms by several years. The relationship between hyposmia and PD remains elusive. Olfactory bulb (OB) pathology shows an increased number of olfactory dopaminergic cells, protein aggregates and dysfunction of neurotransmitter systems. In this study we examined tissue levels of dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) and their metabolites, of noradrenaline (NA) and of the amino acid neurotransmitters aspartate, glutamate, taurine and γ-aminobutyric acid in OBs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated Macaca fascicularis in different stages, includin g monkeys who were always asymptomatic, monkeys who recovered from mild parkinsonian signs, and monkeys with stable moderate or severe parkinsonism. DA was increased compared to controls, while neither NA and 5-HT nor the amino acid neurotransmitters were significantly changed. Furthermore, DA increased before stable motor deficits appear with +51% in asymptomatic and +96% in recovered monkeys. Unchanged DA metabolites suggest a special metabolic profile of the newly formed DA neurons. Significant correlation of homovanillic acid (HVA) with taurine single values within the four MPTP groups and of aspartate with taurine within the asymptomatic and recovered MPTP groups, but not within the controls suggest interactions in the OB between taurine and the DA system and taurine and the excitatory neurotransmitter triggered by MPTP. This first investigation of OB in various stages after MPTP administration suggests that the DA increase seems to be an early phenomenon, not requiring profound nigrostriatal neurodegeneration or PD symptoms.This work was funded by grants from the Ministerio de Economía y Competitividad: SAF2015-67239-P; Instituto de Salud Carlos III (CIBERNED) SAF2016-78207, Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III—Fondos FEDER, a way to build Europe FIS PIE14/00034 to JAO and by the chair UAM-Fundación Tatiana Pérez de Guzmán el Bueno to C