Although type 1 cannabinoid receptors (CB1Rs) are expressed abundantly throughout the brain, the presence of type 2 cannabinoid receptors (CB2Rs) in neurons is still somewhat controversial. Taking advantage of newly designed CB1R and CB2R mRNA riboprobes, we demonstrate by PCR and in situ hybridization that transcripts for both cannabinoid receptors are present within labeled pallidothalamic-projecting neurons of control and MPTP-treated macaques, whereas the expression is markedly reduced in dyskinetic animals. Moreover, an in situ proximity ligation assay was used to qualitatively assess the presence of CB1Rs and CB2Rs, as well as CB1R–CB2R heteromers within basal ganglia output neurons in all animal groups (control, parkinsonian and dyskinetic macaques). A marked reduction in the number of CB1Rs, CB2Rs and CB1R–CB2R heteromers was found in dyskinetic animals, mimicking the observed reduction in CB1R and CB2R mRNA expression levels. The fact that chronic levodopa treatment disrupted CB1R–CB2R heteromeric complexes should be taken into consideration when designing new drugs acting on cannabinoid receptor heteromers.

Continued and intermittent (12 h per day) ozone treatments (2 ppm) to control postharvest decay have been assayed during the storage of 'Superior Seedless', 'Cardinal CL80,' and 'Regina Victoria' table grapes (Vitis vinifera L.) at 5 C for 72 days. The effects of these treatments on the main fruit quality parameters, including resveratrol content, were monitored. Both ozone treatments considerably reduced decay of cold stored grapes compared to those kept in air, continuous ozone treatment being the most effective for controlling postharvest losses. Intermittent ozone treatment induced the highest resveratrol content in stored grapes. On the contrary, ozone-treated grapes got lower scores in the sensory evaluation tests and also showed significantly higher weight losses than the fruits kept in air.

Grape seeds represent a high percentage (20% to 26%) of the grape marc obtained as a byproduct from white winemaking and keep a vast proportion of grape polyphenols. In this study, seeds obtained from 11 monovarietal white grape marcs cultivated in Northwestern Spain have been analyzed in order to characterize their polyphenolic content and antioxidant activity. Seeds of native (Albariño, Caiño, Godello, Loureiro, Torrontés, and Treixadura) and non-native (Chardonnay, Gewurtzträminer, Pinot blanc, Pinot gris, and Riesling) grape varieties have been considered. Low weight phenolics have been extracted by means of pressurized liquid extraction (PLE) and further analyzed by LC-MS/MS. The results showed that PLE extracts, whatever the grape variety of origin, contained large amounts of polyphenols and high antioxidant activity. Differences in the varietal polyphenolic profiles were found, so a selective exploitation of seeds might be possible.

A stereotaxic brain atlas of the basal ganglia and thalamus of Macaca fascicularis presented here is designed with a surgical perspective. In this regard, all coordinates have been referenced to a line linking the anterior and posterior commissures (ac–pc line) and considering the center of the ac at the midline as the origin of the bicommissural space. The atlas comprises of 43 different plates (19 coronal levels, 10 sagittal levels and 14 horizontal levels). In addition to ‘classical’ cyto- and chemoarchitectural techniques such as the Nissl method and the acetylcholinesterase stain, several immunohistochemical stains have been performed in adjacent sections, including the detection of tyrosine hydroxylase, enkephalin, neurofilaments, parvalbumin and calbindin. In comparison to other existing stereotaxic atlases for M. fasicularis, this atlas has two main advantages: firstly, brain cartography is based on a wide variety of cyto- and chemoarchitectural stains carried out on adjacent sections, therefore enabling accurate segmentation. Secondly and most importantly, sagittal and horizontal planes are included. Sagittal planes are very useful for calculating oblique trajectories, whereas, clinical researchers engaged in neuroimaging studies will be more familiar with horizontal sections, as they use horizontal (also called “axial”) brain images in their daily routine of their clinical practices.

Mutations in the GBA1 gene coding for glucocerebrosidase (GCase) are the main genetic risk factor for Parkinson’s disease (PD). Indeed, identifying reduced GCase activity as a common feature underlying the typical neuropathological signatures of PD—even when considering idiopathic forms of PD—has recently paved the way for designing novel strategies focused on enhancing GCase activity to reduce alpha-synuclein burden and preventing dopaminergic cell death. Here we have performed bilateral injections of a viral vector coding for the mutated form of alpha-synuclein (rAAV9-SynA53T) for disease modeling purposes, both in mice as well as in nonhuman primates (NHPs), further inducing a progressive neuronal death in the substantia nigra pars compacta (SNpc). Next, another vector coding for the GBA1 gene (rAAV9-GBA1) was unilaterally delivered in the SNpc of mice and NHPs one month after the initial insult, together with the contralateral delivery of an empty/null rAAV9 for control purposes. Obtained results showed that GCase enhancement reduced alpha-synuclein burden, leading to improved survival of dopaminergic neurons. Data reported here support using GCase gene therapy as a disease-modifying treatment for PD and related synucleinopathies, including idiopathic forms of these disorders.

It is without any doubt that precision medicine therapeutic strategies targeting neurodegenerative disorders are currently witnessing the spectacular rise of newly designed approaches based on the use of viral vectors as Trojan horses for the controlled release of a given genetic payload. Among the different types of viral vectors, adeno-associated viruses (AAVs) rank as the ones most commonly used for the purposes of either disease modeling or for therapeutic strategies. Here, we reviewed the current literature dealing with the use of AAVs within the field of Parkinson’s disease with the aim to provide neuroscientists with the advice and background required when facing a choice on which AAV might be best suited for addressing a given experimental challenge. Accordingly, here we will be summarizing some insights on different AAV serotypes, and which would be the most appropriate AAV delivery route. Next, the use of AAVs for modeling synucleinopathies is highlighted, providing potential readers with a landscape view of ongoing pre-clinical and clinical initiatives pushing forward AAV-based therapeutic approaches for Parkinson’s disease and related synucleinopathies.

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We report a family with branchial myoclonus, spastic paraparesis, and cerebellar ataxia in which six members were affected in two generations and the inheritance appeared to be autosomal dominant. Age at onset ranged from 40 to 50 years. Rhythmic myoclonus involving the palate, pharynx, larynx, and face was followed by truncal ataxia and spastic paraparesis in most patients. CT and MRI revealed mild atrophy of the cerebral and cerebellar cortex and severe atrophy of the medulla and spinal cord. The pons appeared normal and the olives not hypertrophic. CSF studies revealed severe reduction of the serotonin metabolite 5-hydroxyindoleacetic acid. Treatment with 5-hydroxytryptophan and carbidopa at highest tolerated dose mildly improved ataxia but did not modify the myoclonus. Treatment with anticholinergics, benzodiazepines, phenytoin, valproate, carbamazepine, and baclofen was unsuccessful. The clinical symptoms were progressive, leading to death or severe disability 5 to 10 years after the onset of the disease.