Dystonia: sparse synapses for D2 receptors in striatum of a DYT1 knock-out mouse model

Dystonia pathophysiology has been partly linked to downregulation and dysfunction of dopamine D2 receptors in striatum. We aimed to investigate the possible morpho-structural correlates of D2 receptor downregulation in the striatum of a DYT1 Tor1a mouse model. Adult control Tor1a+/+ and mutant Tor1a+/− mice were used. The brains were perfused and free-floating sections of basal ganglia were incubated with polyclonal anti-D2 antibody, followed by secondary immune-fluorescent antibody. Confocal microscopy was used to detect immune-fluorescent signals. The same primary antibody was used to evaluate D2 receptor expression by western blot. The D2 receptor immune-fluorescence appeared circumscribed in small disks (~0.3–0.5 μm diameter), likely representing D2 synapse aggregates, densely distributed in the striatum of Tor1a+/+ mice. In the Tor1a+/− mice the D2 aggregates were significantly smaller (μm2 2.4 ± SE 0.16, compared to μm2 6.73 ± SE 3.41 in Tor1a+/+) and sparse, with ~30% less number per microscopic field, value correspondent to the amount of reduced D2 expression in western blotting analysis. In DYT1 mutant mice the sparse and small D2 synapses in the striatum may be insufficient to “gate” the amount of presynaptic dopamine release diffusing in peri-synaptic space, and this consequently may result in a timing and spatially larger nonselective sphere of influence of dopamine action

Linking migraine to gut dysbiosis and chronic non-communicable diseases

In the world, migraine is one of the most common causes of disability in adults. To date, there is no a single cause for this disorder, but rather a set of physio-pathogenic triggers in combination with a genetic predisposition. Among the factors related to migraine onset, a crucial role seems to be played by gut dysbiosis. In fact, it has been demonstrated how the intestine is able to modulate the central nervous system activities, through the gut-brain axis, and how gut dysbiosis can influence neurological pathologies, including migraine attacks. In this context, in addition to conventional pharmacological treatments for migraine, attention has been paid to an adjuvant therapeutic strategy based on different nutritional approaches and lifestyle changes able to positively modulate the gut microbiota composition. In fact, the restoration of the balance between the different gut bacterial species, the reconstruction of the gut barrier integrity, and the control of the release of gut-derived inflammatory neuropeptides, obtained through specific nutritional patterns and lifestyle changes, represent a possible beneficial additive therapy for many migraine subtypes. Herein, this review explores the bi-directional correlation between migraine and the main chronic non-communicable diseases, such as diabetes mellitus, arterial hypertension, obesity, cancer, and chronic kidney diseases, whose link is represented by gut dysbiosis

Corrigendum to “Pollen-based paleoenvironmental and paleoclimatic change at Lake Ohrid (south-eastern Europe) during the past 500 ka” published in Biogeosciences, 13, 1423–1437, 2016

In this corrigendum we report an updated pollen record from the Lake Ohrid DEEP site spanning the past 500 ka whereby we have reprocessed and re-analyzed 104 samples affected by chemical procedure problems that occurred in one palynological laboratory. Firstly, these samples were affected by the use of wrong containers, causing in- adequate settling of particles at the set centrifuging speed. Secondly, HCl and HF treatments were combined without the prescribed intermediate centrifuging and decanting steps. The inaccuracy in the protocol resulted in the loss of smaller pollen grains and in the overrepresentation of bisaccate ones in most of the re-analyzed samples. We therefore provide an updated set of figures with the new data and have revised the description of the results, discussion and conclusions re- ported in Sadori et al. (2016) where necessary. We stress that the majority of the original results and conclusions remain valid, while the records’ reliability and resolution have improved as 12 samples that had been omitted in the original study because of low count sums are now included in the revised dataset (Sadori et al., 2018)

Effect of segmental muscle vibration on upper extremity functional ability poststroke: A randomized controlled trial.

Abstract Background: Upper extremity functional impairments are common consequences of stroke. Therefore, continuous investigation of effective interventions for upper extremity functions after stroke is a necessity. Segmental muscle vibration (SMV) is one of the interventions that incorporate sensory stimulation to improve motor cortical excitability. The aim of this study was to investigate the influence of 5-minute SMV application along with supervised physical therapy (SPT) on improving activities of daily living and motor recovery on the hemiparetic upper extremity in patients with stroke. Methods: A sample of 37 patients poststroke (29 males) was randomly allocated to either SPT control group (n=18) or SPT and SMV (SPT-SMV) experimental group (n=19). All patients received 3 sessions per week of SPT for 8 weeks. The SPT-SMV experimental group received SMV at the end of each SPT session. Outcome measures used were Barthel index (BI), modified Ashworth scale, manual muscle testing, and goniometry for range of motion (ROM) assessment. Results: Thirty-four patients completed the study. Patients in both groups improved significantly after treatment in BI, elbow ROM, and elbow muscles strength. However, muscle tone in elbow joint of the hemiplegic upper extremity improved significantly after SMV only in the experimental group (SPT-SMV). Conclusion: The SPT intervention can improve functional outcomes of upper extremity in people after stroke. However, using SMV may have superior effect on improving muscle tone after stroke. Abbreviations: ADL = activities of daily living, BI = Barthel index, MAS = modified Ashworth scale, MMT = manual muscle testing, ROM = range of motion, SMV = segmental muscle vibration, SPT = supervised physical therapy, SPT-SMV = supervised physical therapy and segmental muscle vibration

Dopamine D_2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive 4 nicotinic receptors via a cholinergic-dependent mechanism

Recent studies suggest that high-affinity neuronal nicotinic acetylcholine receptors (nAChRs) containing α4 and β2 subunits (α4β2*) functionally interact with G-protein-coupled dopamine (DA) D_2 receptors in basal ganglia. We hypothesized that if a functional interaction between these receptors exists, then mice expressing an M2 point mutation (Leu9'Ala) rendering 4 nAChRs hypersensitive to ACh may exhibit altered sensitivity to a D_2-receptor agonist. When challenged with the D_(2)R agonist, quinpirole (0.5–10 mg/kg), Leu9'Ala mice, but not wild-type (WT) littermates, developed severe, reversible motor impairment characterized by rigidity, catalepsy, akinesia, and tremor. While striatal DA tissue content, baseline release, and quinpirole-induced DA depletion did not differ between Leu9'Ala and WT mice, quinpirole dramatically increased activity of cholinergic striatal interneurons only in mutant animals, as measured by increased c-Fos expression in choline acetyltransferase (ChAT)-positive interneurons. Highlighting the importance of the cholinergic system in this mouse model, inhibiting the effects of ACh by blocking muscarinic receptors, or by selectively activating hypersensitive nAChRs with nicotine, rescued motor symptoms. This novel mouse model mimics the imbalance between striatal DA/ACh function associated with severe motor impairment in disorders such as Parkinson’s disease, and the data suggest that a D_(2)R–α4*-nAChR functional interaction regulates cholinergic interneuron activity.—Zhao-Shea, R., Cohen, B. N., Just, H., McClure-Begley, T., Whiteaker, P., Grady, S. R., Salminen, O., Gardner, P. D., Lester, H. A., Tapper, A. R. Dopamine D2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive α4 nicotinic receptors via a cholinergic-dependent mechanism

Pregnancy, fertile life factors, and associated clinical course in PRKN early-onset Parkinson’s disease

introduction: as the most common cause of autosomal recessive early onset parkinson’s disease (EOPD), parkin type parkinson’s disease (PRKN-PD) may affect female patients in childbearing age. accordingly, issues related to fertility must be adequately addressed. here, we landscaped fertile life factors and pregnancy course of a PRKN-PD cohort, including both novel cases directly observed at our center and published ones. methods: six patients with confirmed PRKN-PD were examined by a structured interview on reproductive factors and associated modifications of PD disturbances, including one case followed up throughout pregnancy which was described in greater detail. six studies reporting fertile life factors of nine PRKN-PD patients were reviewed collecting homogeneous data on fertile life and pregnancy course. results: PRKN-PD female patients experienced motor fluctuations with the menstrual cycle, pregnancy, and puerperium, which suggests a role for sex hormones in PD clinical burden. In some cases, abortion and miscarriages occurred during the organogenesis phase in patients receiving oral antiparkinsonian therapy; however, levodopa/benserazide monotherapy resulted to be the safest choice in pregnancy. conclusion: collectively these data disclose the importance of pre-conception counseling in childbearing age PRKN-PD patients and EOPD in general