Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knock-out mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.

Hiperidrose compensatória após simpatectomia toracoscópica: características, incidência e influência na satisfação do paciente

Hyperhidrosis is an idiopathic condition characterized by excessive sweating. Symptoms generally begin in childhood or early adolescence, and rarely improve with age. The excessive localized sweating generally occurs either spontaneously, or in association with stressful or emotionally charged situations. This prospective study aimed to investigate predictive factors for compensatory hyperhidrosis after thoracoscopic sympathicotomy. From 2000 to 2002, 80 patients (53 female and 27 male) underwent hyperhidrosis surgery. The patients, ranging from 12 to 56 years old, were studied and followed-up for 42.51 ±5.98 months. A satisfaction grading using a visual analogue scale -VAS (0 = not at all satisfied, and 10 = fully satisfied) was used. The surgical procedure was performed bilaterally on the second ganglion (T2) for facial hyperhidrosis, on the third and fourth ganglia (T3 and T4) for axillary hyperhidrosis, and on the third ganglion (T3) for palmar hyperhidrosis. The results showed that, 68 patients (85%) presented with compensatory sweating (CS), which was classified as mild (33.8%), moderate (33.8%) and severe (32.4%). Considering the final surgical results, 70 patients (87.5%) were satisfied with the outcome of the operation, while 10 patients (12.5%) were dissatisfied. Degrees of satisfaction varied according to sex, age, BMI and extent of denervation. Moreover, the compensatory hyperhidrosis was more severe in abdomen and back than in legs. In conclusion, although CS is a frequent adverse effect of sympathicotomy, the degree of patient satisfaction was high. Some factors were related to the occurrence and severity of CS and the most adequate patients to be submitted to this operation are young adult women whose BMI is less than 24.9

Efeitos da simpaticotomia endoscópica sobre as artérias caróticas e vertebrais na terapêutica cirúrgica da hiperidrose primária

Analyze, in patients with primary hyperhidrosis (PH) who was undergone to videothoracoscopic sympathicotomy, the degree of vascular denervation after surgical transection of the thoracic sympathetic chain by measuring ultrasonografic parameters in carotid and vertebral arteries. Methods: Twenty-four patients with PH underwent forty-eight endoscopic thoracic sympathicotomy and were evaluated by duplex eco-doppler measuring systolic peak velocity (SPV), diastolic peak velocity (DPV), pulsatility index (PI) and resistivity index (RI) in bilateral common, internal and external carotids, besides bilateral vertebral arteries. The exams were performed before operations and a month later. Wilcoxon test was used to analyse the differences between the variables before and after the sympatholisis. Results: T3 sympathicotomy segment was the most frequent transection done (95,83%), as only ablation (25%) or in association with T4 (62,50%) or with T2 (8,33%). It was observed increase in RI and PI of the common carotid artery ( p<0,05). The DPV of internal carotid artery decreased in both sides (p<0,05). The SPV and the DPV of the right and left vertebral arteries also increased (p<0,05). Asymmetric findings were observed so that, arteries of the right side were the most frequently affected. Conclusions: Hemodynamic changes in vertebral and carotid arteries were observed after sympathicotomy for PH. SPV was the most often altered parameter, mostly in the right side arteries, meaning significant asymmetric changes in carotid and vertebral vessels. Therefore, the research findings deserve further investigations to observe if they have clinical inferences

Força muscular respiratória, qualidade de vida e modulação autonômica da frequência cardíaca na distrofia miotônica

Background: The myotonic dystrophy (MD) is a multisystem neuromuscular disease that can affect the respiratory muscles and heart function, and cause impairment in quality of life. Objectives: Investigate the changes in respiratory muscle strength, health-related quality of life (HRQoL) and autonomic modulation heart rate (HR) in patients with MD. Methods: Twenty-three patients performed assessment of pulmonary function, sniff nasal inspiratory pressure (SNIP), the maximal inspiratory (MIP) and expiratory (MEP) pressure, and of HRQoL (SF-36 questionnaire). Of these patients, 17 underwent assessment of heart rate variability (HRV) at rest, in the supine and seated positions. Results: The values of respiratory muscle strength were 64, 70 and 80% of predicted for MEP, MIP, and SNIP, respectively. Significant differences were found in the SF-36 domains of physical functioning (58.7 ± 31,4 vs. 84.5 ± 23, p<0.01) and physical problems (43.4 ± 35.2 vs. 81.2 ± 34, p<0.001) when patients were compared with the reference values. Single linear regression analysis demonstrated that MIP explains 29% of the variance in physical functioning, 18% of physical problems and 20% of vitality. The HRV showed that from supine position to seated, HF decreased (0.43 x 0.30), and LF (0.57 x 0.70) and the LF/HF ratio (1.28 x 2.22) increased (p< 0.05). Compared to healthy persons, LF was lower in both male patients (2.68 x 2.99) and women (2.31 x 2.79) (p< 0.05). LF / HF ratio and LF were higher in men (5.52 x 1.5 and 0.8 x 0.6, p <0.05) and AF in women (0.43 x 0.21) (p< 0.05). There was positive correlation between the time of diagnosis and LF / HF ratio (r = 0.7, p <0.01). Conclusions: The expiratory muscle strength was reduced. The HRQoL was more impaired on the physical aspects and partly influenced by changes in inspiratory muscle strength. The HRV showed that may be sympathetic dysfunction in autonomic modulation of HR, although with normal adjustment of autonomic modulation during the change of posture. The parasympathetic modulation is higher in female patients and sympathetic tends to increase in patients with longer diagnosis

Estudo dos efeitos comportamentais do neuropeptídeos em camundongos submetidos a modelos animais de Parkinson

Neuropeptide S (NPS) is the endogenous ligand of a G-protein coupled receptor. Preclinical studies have shown that NPSR receptor activation can promote arousal, anxiolytic-like behavioral, decrease in food intake, besides hyperlocomotion, which is a robust but not well understood phenomenon. Previous findings suggest that dopamine transmission plays a crucial role in NPS hyperactivity. Considering the close relationship between dopamine and Parkinson Disease (PD), and also that NPSR receptors are expressed on dopaminergic nuclei in the brain, the current study attempted to investigate the effects of NPS in motor deficits induced by intracerebroventricular (icv) administration of 6-OHDA and systemic administration of haloperidol. Motor deficits induced by 6-OHDA and haloperidol were evaluated on Swiss mice in the rota-rod and catalepsy test. Time on the rotating rod and time spent immobile in the elevated bar were measured respectively in each test. L-Dopa, a classic antiparkinsonian drug, and NPS were administrated in mice submitted to one of the animal models of PD related above. 6-OHDA injection evoked severe motor impairments in rota-rod test, while the cataleptic behavior of 6-OHDA injected mice was largely variable. The administration of L-Dopa (25 mg/kg) and NPS (0,1 and 1 nmol) reversed motor impairments induced by 6-OHDA in the rota-rod. Haloperidolinduced motor deficits on rota-rod and catalepsy tests which were reversed by L-Dopa (100 e 400 mg/kg), but not by NPS (0,1 and 1 nmol) administration. The association of L-Dopa 10 mg/kg and NPS 1 nmol was also unable to counteract haloperidol-induced motor deficits. To summarize, 6-OHDA-, but not haloperidol-, induced motor deficits were reversed by the central administration of NPS. These data suggest that NPS possibly facilitates dopamine release in basal ganglia, what would explain the overcome of motor performance promoted by NPS administration in animals pretreated with 6-OHDA, but not haloperidol. Finally, the presented findings point, for the first time, to the potential of NPSR agonist as an innovative treatment for PD.