Transcranial magnetic stimulation and aging: Effects on spatial learning and memory after sleep deprivation in Octodon degus.

The benefits of neuromodulatory procedures as a possible therapeutic application for cognitive rehabilitation have increased with the progress made in non-invasive modes of brain stimulation in aged-related disorders. Transcranial magnetic stimulation (TMS) is a non-invasive method used to examine multiple facets of the human brain and to ameliorate the impairment in cognition caused by Alzheimer's disease (AD). The present study was designed to evaluate how a chronic TMS treatment could improve learning and memory functions after sleep deprivation (SD) in old Octodon degus. SD was executed by gently handling to keep the animals awake throughout the night. Thirty young and twenty-four old O. degus females were divided in six groups (control, acute and chronic TMS treatment). Behavioral tests included; Radial Arm Maze (RAM), Barnes Maze (BM) and Novel Object Recognition (NOR). Although learning and memory functions improved in young animals with only one session of TMS treatment, a significant improvement in cognitive performance was seen in old animals after 4 and 7days of TMS, depending on the task that was performed. No side effects were observed following, which showed therapeutic potential for improving age-related cognitive performance.

Evidence of oligodendrogliosis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism.

AIMS: Mice and nonhuman primates administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) represent elective experimental models of Parkinsonism, in which degeneration of the nigrostriatal dopaminergic pathway is associated with prominent neuroinflammation, characterized by activated microglia and astrocytes in both substantia nigra (SN) and striatum. To date, it is unknown whether oligodendrocytes play a role in these events. METHODS: We performed a detailed qualitative and quantitative analysis of oligodendrocyte-associated changes induced by acute and chronic MPTP treatment, in the SN and striatum of mice and macaques respectively. Oligodendrocytes were immunolabelled by cell-specific markers and analysed by confocal microscopy. RESULTS: In both experimental models, MPTP treatment induces an increase in oligodendrocyte cell number and average size, as well as in the total area occupied by this cell type per tissue section, accompanied by evident morphological changes. This multifaceted array of changes, herein referred to as oligodendrogliosis, significantly correlates with the reduction in the level of dopaminergic innervation to the striatum. CONCLUSIONS: This event, associated with early damage of the dopaminergic neurone axons and of the complex striatal circuits of which they are part, may result in an important, although neglected, aspect in the onset and progression of Parkinsonism.

[Colorectal cancer in Spain: Temporary disability and preventive occupational strategies]. / El cáncer colorrectal en España. Costes por incapacidad temporal y opciones preventivas desde las empresas.

BACKGROUND: Colorectal cancer is one of the most frequent cancers in both sexes and the most frequent in the developed countries, if men and women are considered together as a group. It has an important associated morbidity and mortality in all countries and constitutes a public health problem with a high direct and indirect economic cost. The number of workdays lost due to temporary disability (TD) is one of the quantifiable references of these indirect costs. AIMS: To determine the indirect cost associated with TD due to colorectal cancer in Spain during the year 2011, a cost that aids in the prevention cost/benefit estimation. METHODS: The number of TD processes, the number of workdays lost due to TD, and the mean duration of those processes, based on the CIE 9-MC codes related to this pathology, as well as the calculated cost, using the Spanish minimum wage as a reference, during the period of January to December 2011, were all reviewed. RESULTS: Colorectal cancer in Spain during 2011 represented 1,046 TD processes, 202,784 workdays lost, and a mean process duration of 194 days/year. The resulting cost of the pathology due to TD was 4,335,521.92 euros. CONCLUSIONS: These results are beneficial for evaluating the usefulness of implementing public health support strategies for a greater reduction in colorectal cancer prevalence and mortality, and an improvement in quality of life of the affected individuals and their families, together with an economic savings resulting from a reduction in TD as a consequence of this disease.

7-Nitroindazole reduces L-DOPA-induced dyskinesias in non-human Parkinsonian primate.

Nitric oxide (NO) plays a pivotal role in integrating dopamine transmission in the basal ganglia and has been implicated in the pathogenesis of Parkinson disease (PD). The objective of this study was to ascertain whether the NO synthase inhibitor, 7-nitroindazole (7-NI), is able to reduce L-DOPA-induced dyskinesias (LIDs) in a non-human primate model of PD chronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Six Parkinsonian macaques were treated daily with L-DOPA for 3-4 months until they developed LIDs. Three animals were then co-treated with a single dose of 7-NI administered 45 min before each L-DOPA treatment. Dyskinetic MPTP-treated monkeys showed a significant decrease in LIDs compared with their scores without 7-NI treatment (p < 0.05). The anti-Parkinsonian effect of L-DOPA was similar in all three monkeys with and without 7-NI co-treatment. This improvement was significant with respect to the intensity and duration of LIDs while the beneficial effect of L-DOPA treatment was maintained and could represent a promising therapy to improve the quality of life of PD patients.

[Visceral adiposity index (VAI) and dysfunctional adiposity index (DAI). Relationship with obesity parameters]. / Relación de los índices de adiposidad visceral (VAI) y disfuncional (DAI) con parámetros de obesidad.

INTRODUCTION: Obesity is a global pandemic with a growing impact on morbidity and mortality. We assessed the associative strength of the Visceral Adiposity Index (VAI) and Dysfunctional Adiposity Index (DAI) in obesity and associated risk using different methods. MATERIAL AND METHODS: Cross-sectional study in 418 343 workers from different autonomous communities in Spain, estimating prevalence of obesity with: waist circumference, waist/height index, BMI, CUN-BAE, ECORE-BF, RFM, PALAFOLLS, IMG, METS-VF calculated according to their specific formulas. Descriptive analysis of categorical variables and associative strength of VAI and DAI for obesity was performed with ROC curves considering high risk when the AUC value.0.8 and moderate with AUC.0.7 and.0.8. SPSS 27.0 was used, considering statistical significance p.0.05. RESULTS: The prevalence of obesity varied according to the method used, being high with Palafolls (72.92% in women and 86.98% in men) and low with METS-VF (1.31% in women and 8.54% in men). The mean values of VAI and DAI are always higher in men. The AUC of the ROC curve for VAI was high with METS-VF: in women 0.836 (95%CI 0.829-0.843), in men 0.848 (95%CI 0.845-0.850) and with waist circumference in men: 0.819 (95%CI 0.816-0.822). DAI was high for METS-FV in women: 0.809 (95%CI 0.801-0.817). CONCLUSIONS: The prevalence of obesity and related risk differs according to the assessment method used. VAI shows high strength of association with obesity and fat mass for METS-VF in both sexes and with waist circumference in men; DAI for METS-VF in women.

[Prevalence of diabesity in the Spanish working population: influence of sociodemographic variables and tobacco consumption].

BACKGROUND: Obesity predisposes to type 2 diabetes so often that the combination is called diabesity. The aim of this study was to determine the prevalence of diabesity in the working population and to analyze the variables associated with it. METHOD: Cross-sectional study between January 2019 and June 2020 by 418,343 workers from 18 to 67 year-old, from different professions and Spanish geographic areas. The prevalence of diabesity was determined with six different for-mulae for obesity: BMI (body mass index), CUN BAE (Clínica Universidad de Navarra Body Adiposity Estimator), ECORE-BF (Equation Córdoba for Estimation of Body Fat), Formula Palafolls, FMI (fat mass index) of Deuremberg and RFM (relative fat mass). The association between diabetes and age, sex, social class and tobacco was analyzed. RESULTS: The global prevalence of diabetes ranged from 2.6% for BMI to 5.8% for the Palafolls formula. The variable most related to diabesity was age over 50 years (OR?=?5.9; 95%CI: 5.7-6.2 for BMI, and OR?=?8.1; 95%CI: 7.9-8.4 for FMI of Deuremberg). Male sex and social class III related with diabesity estimated by all formulas, while being a smoker was only related with the Palafolls formula. CONCLUSION: Diabesity prevalence varies depending on the formula used, with much lower prevalence among women and increased with age independent of the formula used. Its prevalence is higher in the lower social classes.

Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation, Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice.

Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson's disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Graphical Abstract MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.

Identification of differentially expressed genes profiles in a combined mouse model of Parkinsonism and colitis.

Different cellular mechanisms have been described as being potentially involved in the progression of neurodegeneration in Parkinson's disease, although their role is still unclear. The present study aimed to identify in detail, through differentially expressed genes analysis by bioinformatics approaches, the molecular mechanisms triggered after a systemic insult in parkinsonian mice. To address this objective, we combined a dextran sodium sulfate (DSS)-induced ulcerative colitis experimental mice model with an acute 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP) intoxication. The animals were divided into four experimental groups based on the different treatments: (i) control, (ii) DSS, (iii) MPTP and (iv) MPTP + DSS. The data obtained by microarray and functional enrichment analysis point out the implication of different molecular mechanisms depending on the experimental condition. We see, in the striatum of animals intoxicated only with DSS, dysfunction processes related to the blood. On the other hand, oxidative stress processes are more prominent at the MPTP intoxicated mice. Finally, differentially expressed genes within the MPTP + DSS show functional enrichment in inflammation and programmed cell death. Interestingly, we identify a significant synergistic negative effect of both toxins since the expression of differentially expressed genes (DEGs) related to balanced cellular homeostasis was not enough to prevent processes associated with cell death. This work provides detailed insights into the involvement of systemic inflammation, triggered after an insult in the colon, in the progression of the degeneration in Parkinsonism. In this way, we will be able to identify promising therapeutic targets that prevent the contribution of inflammatory processes in the progression of Parkinson's disease.

[Migraine medical control and related variables. Results of the European Work and Migraine survey]. / Control médico en migraña y variables relacionadas. Resultados de la encuesta europea Trabajo y Migraña.

OBJECTIVE: This purpose of this work is to determine the care preferences and the required use of medical care by migraine patients in the different countries of Europe, and the observed differences depending on their social and demographic conditions. MATERIAL AND METHODS: Cross-sectional observational study by anonymous web survey of 3,342 patients from Spain, Italy, France, Portugal, Ireland, United Kingdom, Germany, and a mixed group of countries not included in the initial design. VARIABLES: age, gender, country, type of location, level of studies and rural or urban area. The demand for care is collected by neurologist, primary care doctors/family/general practitioners, by occupational health doctors, nurses, by other doctors/other specialists, non-medical control/self-control. RESULTS: The patients more seen by a neurologist were about 21-60years old and with a high cultural level. Primary care/family doctor care is higher in urban areas. Occupational medicine, nursing, and other specialties predominate in large cities. Self-control is greater in patients aged 21-40years and in women. Spain and Germany are the countries with the greatest demand for care in Neurology and Primary Care. CONCLUSIONS: The medical demand for migraine care in Europe shows irregular results according to countries, with it being a priority in neurology and with less participation of Primary Care physicians, work doctors, nurses, or other specialties. Differences are observed by age, gender, and cultural level both in the demand for care and in the choice of specialist. It is important to take into account the percentage of patients who have no medical control.

Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates.

Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.

Parkinson's disease: a short story of 200 years.

After Alzheimer's disease, Parkinson's disease (PD) is the second most prevalent and incidental neurodegenerative disorder, affecting more than 2% of the population older than 65 years old. Since it was first described 200 years ago by Dr James Parkinson, great steps have been made in the understanding of the pathology. However, the cause(s) that initiates and perpetuates the neurodegenerative process is (are) still not clear. Thus, early diagnosis is not available, nor are there efficient therapies that can stop neurodegeneration. PD clinical features are defined by motor (like bradykinesia, resting tremor, gait impairment) and non-motor symptoms (like constipation, apathy, fathigue, olfactory dysfunction, depression and cognitive decline) that get more severe as the disease advances. Neuropathological hallmarks comprise selective loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc) and Lewy bodies (LB) in different nuclei of the nervous system. Numerous studies have shown that these pathological features are aggravated by the confluence of other contributing factors, such as a genetic component, exposure to environmental toxins, mitochondrial dysfunction, increase of oxidative stress, calcium imbalance and chronic neuroinflammation, among others. Here, we provide a summary of the actual state of PD's pathology, the most studied molecular mechanisms, classic and novel therapeutic strategies and diagnosis methods, especially highlighting recent advances in these 200 years.

Cavernomas in children with brain tumors: a late complication of radiotherapy.

BACKGROUND: Delayed complications of radiation therapy comprise cerebral atrophy, radionecrosis and induction of tumors. Recent reports indicate the possibility of the "de-novo" formation of intracranial cavernomas in patients submitted to radiation therapy to the brain. OBJECTIVES: To report three children, two with medulloblastomas and one with a pineal germinoma, treated with radiotherapy that developed intracerebral cavernous hemangiomas some years after treatment. With this work, we aim to draw attention to this occurrence in the neurosurgical community. RESULTS: The patients were two girls and one boy with ages comprised between 2.5 and 7 years (mean 5.2 years). The average interval from irradiation to the appearance of cavernoma was of 5.3 years (range 5-6 years). The lesions were found during the routine neuroimaging studies performed for the follow-up of their primary neoplasms. No patient showed signs or symptoms related to the cavernomas. However, the three children will need both clinical and neuroimaging surveillance to monitor the evolution of these incidentally discovered lesions. CONCLUSIONS: Intracranial cavernomas can occur years after cerebral radiation therapy. In spite of previous reports that show a high incidence of bleeding lesions, cavernomas may be found incidentally during the neuroimaging surveillance studies that are performed to children with brain tumors previously treated with radiotherapy. In these cases, a conservative attitude seems to be advisable, reserving surgery only for those lesions that grow or bleed.

Alteration of the PAC1 Receptor Expression in the Basal Ganglia of MPTP-Induced Parkinsonian Macaque Monkeys.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-known neuropeptide with strong neurotrophic and neuroprotective effects. PACAP exerts its protective actions via three G protein-coupled receptors: the specific Pac1 receptor (Pac1R) and the Vpac1/Vpac2 receptors, the neuroprotective effects being mainly mediated by the Pac1R. The protective role of PACAP in models of Parkinson's disease and other neurodegenerative diseases is now well-established in both in vitro and in vivo studies. PACAP and its receptors occur in the mammalian brain, including regions associated with Parkinson's disease. PACAP receptor upregulation or downregulation has been reported in several injury models or human diseases, but no data are available on alterations of receptor expression in Parkinson's disease. The model closest to the human disease is the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced macaque model. Therefore, our present aim was to evaluate changes in Pac1R expression in basal ganglia related to Parkinson's disease in a macaque model. Monkeys were rendered parkinsonian with MPTP, and striatum, pallidum, and cortex were evaluated for Pac1R immunostaining. We found that Pac1R immunosignal was markedly reduced in the caudate nucleus, putamen, and internal and external parts of the globus pallidus, while the immunoreactivity remained unchanged in the cortex of MPTP-treated parkinsonian monkey brains. This decrease was attenuated in some brain areas in monkeys treated with L-DOPA. The strong, specific decrease of the PACAP receptor immunosignal in the basal ganglia of parkinsonian macaque monkey brains suggests that the PACAP/Pac1R system may play an important role in the development/progression of the disease.

Electrical stimulation or MK-801 in the inferior colliculus improve motor deficits in MPTP-treated mice.

The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. Additionally, the IC has been implicated in processing sensorimotor responses. Glutamatergic and GABAergic manipulations in the IC can improve motor deficits as demonstrated by the animal model of haloperidol-induced catalepsy. However, how the IC influences motor function remains unclear. We investigated the effects of either intracollicular deep brain stimulation (DBS) or microinjection of the glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After DBS or microinjections, the mice were submitted to rotarod and open field tests, respectively. DBS in the IC was effective to increase the time spent on the rotarod in MPTP-treated mice. After unilateral microinjection of MK-801, but not NMDA, MPTP-treated mice increased the distance travelled in the open field (p < 0.05). In conclusion, intracollicular DBS or MK-801 microinjection can improve motor performance in parkinsonian mice suggesting the IC as a new and non-conventional therapeutic target in motor impairment.

[Blood pressure and sleep apnoea hypopnoea syndrome in workers. STOP-Bang test versus Epworth test]. / Presión arterial y síndrome de apnea-hipopnea del sueño en trabajadores. Test STOP-Bang frente a la escala de Epworth.

INTRODUCTION: OSAHS is associated with an increased risk of cardiovascular disease and stroke. Arterial hypertension is a key risk factor to consider due to its impact on health. METHOD: Cross-sectional study carried out on Spanish public service workers. The nocturnal apnoea risk using the Epworth and STOP-Bang questionnaires and their influence on the mean values of blood pressure are assessed. RESULTS: The detection of OSAHS using the Epworth test and, particularly with the STOP-Bang shows a significant relationship with the mean values of blood pressure, with differences between both questionnaires. CONCLUSION: The Epworth and STOP-Bang questionnaires are useful for the initial detection of OSAHS and a higher prevalence of high blood pressure. Both can be used in screening procedures in occupational health.

[Pain and workplace. Sociodemographic variables influence in therapeutic response and labor productivity]. / Dolor y trabajo. Influencia de variables sociodemográficas en la respuesta terapéutica y la productividad laboral.

INTRODUCTION: Pain is a major cause of medical consultation. The complexity of managing it is due to its long duration and intensity, and it sometimes requires a combination of multiple drugs. The objective of this study is to assess the use of drugs for pain in workers, the clinical response obtained, its influence on estimating work productivity, its relationship to sociodemographic variables, and the type of drug used. MATERIAL AND METHODS: A cross-sectional study on 1,080 workers, aged 18-65 years, during periodic surveys to monitor their health in companies in the service sector in Spain. Treatments used, clinical efficacy, influence on work productivity and sociodemographic variables (age, gender) are evaluated. The Brief Pain Inventory questionnaire, validated for Spain, was used to assess pain, and the SPSS(®) 20.0 package for the statistical analysis. RESULTS: NSAIDs and simple analgesics have higher percentages of improvement in pain (P=.032 and P<.0001, respectively). Men respond better to NSAIDs, and women to simple analgesics. Improved productivity is higher in men than in women (P=.042). No significant differences were observed for age, pain improvement or productivity, except in those over 55 years. CONCLUSIONS: The analgesic prescription pain conditions must consider the age and gender of the patient, as well as the type of drug. The choice of drug should be based on the aetiology and aspects unrelated to the clinical variables, such as sociodemographic, work or psychosocial.

[Occupational disability in epilepsy. The assessment criteria]. / La incapacidad laboral en epilepsia. Criterios de valoración.

Epilepsy is a chronic disease cursing with recurrent and paroxysmal crises due to anomalies in the electrical activity of brain, and is controllable in most of the patients by using antiepileptic drugs, in single or combination therapy. Probably one of the most complex aspects of epilepsy is the assessment of disability for work of the affected person. For this purpose, multiple factors need to be taken into account for homogeneous decision-making, and according to criteria of approval and within the principle of equity inherent in the granting of Social Security disability benefits. This requires the cooperation of all professionals involved in the different specialties, with reports using common criteria and taking into account the disease itself, as well as the effects of the prescribed treatments, the effects of which can contribute to the limitations in the performance of certain professions of risk.

An outstanding catalyst for the oxygen-mediated oxidation of arylcarbinols, arylmethylene and arylacetylene compounds.

A convenient and sustainable protocol for the aerobic oxidation of benzyl alcohols to carbonyl compounds, based on the use of 1,2,4-triazole-type ligands and nickel(II) bromide, is described. This combination leads to the formation of an exceedingly active, enzyme-like system that allows for other oxidative processes, such as benzylic C-H oxidation and oxygen-mediated cleavage of C-C triple bond, a pioneering procedure for transformation of alkynes into carboxylic acids.

Cognitive Impairment After Sleep Deprivation Rescued by Transcranial Magnetic Stimulation Application in Octodon degus.

Sleep is indispensable for maintaining regular daily life activities and is of fundamental physiological importance for cognitive performance. Sleep deprivation (SD) may affect learning capacity and the ability to form new memories, particularly with regard to hippocampus-dependent tasks. Transcranial magnetic stimulation (TMS) is a non-invasive procedure of electromagnetic induction that generates electric currents, activating nearby nerve cells in the stimulated cortical area. Several studies have looked into the potential therapeutic use of TMS. The present study was designed to evaluate how TMS could improve learning and memory functions following SD in Octodon degus. Thirty juvenile (18 months old) females were divided into three groups (control, acute, and chronic TMS treatment-with and without SD). TMS-treated groups were placed in plastic cylindrical cages designed to keep them immobile, while receiving head magnetic stimulation. SD was achieved by gently handling the animals to keep them awake during the night. Behavioral tests included radial arm maze (RAM), Barnes maze (BM), and novel object recognition. When TMS treatment was applied over several days, there was significant improvement of cognitive performance after SD, with no side effects. A single TMS session reduced the number of errors for the RAM test and improved latency and reduced errors for the BM test, which both evaluate spatial memory. Moreover, chronic TMS treatment brings about a significant improvement in both spatial and working memories.

Alterations of GABAergic neurons in the basal ganglia of patients with progressive supranuclear palsy: an in situ hybridization study of GAD67 messenger RNA.

We analyzed postmortem GABAergic neurons in the basal ganglia of three patients with progressive supranuclear palsy (PSP) and four matched controls by means of glutamic acid decarboxylase (M(r) 67,000 [GAD67]) mRNA in situ hybridization. In PSP, we found a 50 to 60% decrease in the number of neurons expressing GAD67 mRNA in the caudate nucleus, ventral striatum, and the external and internal pallidum. The expression of GAD67 mRNA per neuron was reduced in the caudate nucleus and putamen (-43%), the ventral striatum (-55%), and the external and internal pallidum (-59% and -68%). Our data indicate that striatal and pallidal GABAergic neurotransmission is markedly reduced in PSP and we suggest that this alteration may account for the motor and cognitive symptoms observed in PSP. Furthermore, the destruction of the basal ganglia output systems may explain the lack of responsiveness to L-dopa therapy of PSP patients.