Targeting NAAA counters dopamine neuron loss and symptom progression in mouse models of parkinsonism.

The lysosomal cysteine hydrolase N-acylethanolamine acid amidase (NAAA) deactivates palmitoylethanolamide (PEA), a lipid-derived PPAR-α agonist that is critically involved in the control of pain and inflammation. In this study, we asked whether NAAA-regulated PEA signaling might contribute to dopamine neuron degeneration and parkinsonism induced by the mitochondrial neurotoxins, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In vitro experiments showed that 6-OHDA and MPTP enhanced NAAA expression and lowered PEA content in human SH-SY5Y cells. A similar effect was observed in mouse midbrain dopamine neurons following intra-striatal 6-OHDA injection. Importantly, deletion of the Naaa gene or pharmacological inhibition of NAAA activity substantially attenuated both dopamine neuron death and parkinsonian symptoms in mice treated with 6-OHDA or MPTP. Moreover, NAAA expression was elevated in postmortem brain cortex and premortem blood-derived exosomes from persons with Parkinson's disease compared to age-matched controls. The results identify NAAA-regulated PEA signaling as a molecular control point for dopaminergic neuron survival and a potential target for neuroprotective intervention.

Management and Treatment of Patients With Major Depressive Disorder and Chronic Diseases: A Multidisciplinary Approach.

In patients with physical chronic diseases, the prevalence of major depressive disorder (MDD) is approximately 2- to 3-fold higher than in the general population, and it can reach up to 20-40%. The comorbidity of MDD with chronic medical diseases is associated with poorer quality of life, increased medical symptom burden, poor adherence to self-care regimens, increased risk of functional impairment, morbidity, and mortality, and also higher medical costs. Despite this evidence, in routine practice, psychological issues and concerns are frequently inadequately managed. This consensus document proposes that a proper diagnosis, a multidisciplinary approach, and a personalized treatment plan would allow patients with MDD and chronic comorbidities to be more compliant, to improve the outcomes, to reduce possible relapses in the long term, and to prevent or better manage complications and adverse events. This proposal might be useful for any health professionals who deal with patients with chronic diseases, as it can help to pay more attention to the emotional impact of these conditions, in particular in terms of depressive symptoms.

Alpha-synuclein in salivary gland as biomarker for Parkinson's disease.

Estimates of the accuracy of clinical diagnosis of Parkinson's disease (PD) range between 46% and 90%, the accuracy of diagnosis dependent on prolonged clinical observation and clinical response to levodopa. For this reason, we need reliable diagnostic biomarkers. The cardinal hallmark of PD is alpha-synuclein aggregation in the brain. Demonstrating pathological alpha-synuclein in live patients would be useful for identifying and monitoring PD patients. By autopsy studies and in vivo studies, the presence of alpha-synuclein has been demonstrated even outside the central nervous system and the gastro-enteric tract appears to be the most promising candidate tissue for biopsy-taking and the esophagus and salivary glands appear to be the area with the highest concentration of alpha-synuclein. The purpose of our study is to conduct a review to determine the utility of salivary gland biopsy for the histological diagnosis of PD. A computerized medline study was carried out through the use of pubmed: using the MeSH terms: 'salivary gland biopsy for PD', 'PD and dysphagia', 'alpha-synuclein and salivary gland'. We found 9 articles about minor salivary glands and submandibular gland biopsy for diagnosis of PD. According to the results of this review, the submandibular gland biopsy is the test with the increased sensitivity and specificity compared to the biopsy of the minor salivary glands (sensitivity: 0.85 and 0.37 respectability and specificity: 0.96 and 0.94 respectively). New studies are necessary on a wider population to confirm these results.

Relationship of cortical atrophy to fatigue in patients with multiple sclerosis.

BACKGROUND: Fatigue is a common and disabling symptom of multiple sclerosis (MS). Previous studies reported that damage of the corticostriatothalamocortical circuit is critical in its occurrence. OBJECTIVE: To investigate the relationship between fatigue in MS and regional cortical and subcortical gray matter atrophy. DESIGN: Case-control study. SETTING: National Institutes of Health. PARTICIPANTS: Twenty-four patients with MS and 24 matched healthy volunteers who underwent 3.0-T magnetic resonance imaging and evaluations of fatigue (Modified Fatigue Impact Scale) and depression (Center for Epidemiologic Studies Depression Scale). MAIN OUTCOME MEASURES: Relationship between thalamic and basal ganglia volume, cortical thickness of frontal and parietal lobes, and, in patients, T2 lesion volume and normal-appearing white matter volume and the extent of fatigue. RESULTS: Patients were more fatigued than healthy volunteers (P = .04), while controlling for the effect of depression. Modified Fatigue Impact Scale score correlated with cortical thickness of the parietal lobe (r = -0.50, P = .01), explaining 25% of its variance. The posterior parietal cortex was the only parietal area significantly associated with the Modified Fatigue Impact Scale scores. CONCLUSIONS: Cortical atrophy of the parietal lobe had the strongest relationship with fatigue. Given the implications of the posterior parietal cortex in motor planning and integration of information from different sources, our preliminary results suggest that dysfunctions in higher-order aspects of motor control may have a role in determining fatigue in MS.

Hemiparkinsonism due to frontal meningioma.

We describe a case with right hemiparkinsonism due to a frontal meningioma with surrounding edema compressing the basal ganglia. The initial diagnosis of idiopathic Parkinson's disease (PD) was made in another institution on the basis of the positive family history, the clinical symptoms and the asymmetric reduction of striatal tracer binding in a single photon emission computed tomography study for the dopamine transporter. The symptoms of parkinsonism resolved completely shortly after surgery for removal of the tumor. This case points to the significance of structural neuroimaging in the evaluation of parkinsonism even in cases that fulfill all the necessary clinical criteria for idiopathic PD.