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Aim: The apathetic syndrome is a common clinical feature in patients with Alzheimer diseases (AD), from preclinical phases to late stages of dementia, and it is strongly related to major disease outcomes. Unfortunately, no specific pharmacological treatments for apathy have been accomplished so far. Translational evidences have previously shown that a link between apathy and hallmarks of AD-related pathophysiology, that is, β-amyloid (Aβ) plaques and neurofibrillary tangles, exists. However, only few studies investigated the association between core biomarkers of AD and apathy scores, finding conflicting results.Methods: Thirty-seven patients were identified as having AD dementia according to National Institute on Aging-Alzheimer Association 2011 criteria. All participants underwent an extensive diagnostic workup including cerebrospinal fluid (CSF) assessment to measure the concentrations of Aβ42, t-tau, and pTau181. To follow, they were stratified as: apathy absence, apathy mild, and apathy severe according to the Neuro Psychiatric Inventory-apathy item scores. We investigated for potential associations between apathy scores and CSF biomarkers concentrations as well as for differences in terms of clinical and CSF biomarkers data across the 3 apathy groups.Results: The CSF Aβ42 concentrations were negatively correlated with apathy scores. In addition, patients with severe apathy had significantly lower Aβ42 levels compared to nonapathetic ones.Conclusion: Based on our results, we encourage further studies to untangle the potential association between the complex pathophysiological dynamics of AD and apathy which may represent an innovative reliable clinical outcome measure to use in clinical trials, investigating treatments with either a symptomatic or a disease-modifying effect. [ABSTRACT FROM AUTHOR]

Abstract: Palm oil is a carotenoid‐rich natural compound, whose microencapsulation by complex coacervation may protect it against adverse conditions, allowing applications in food formulations for nutritional enrichment and natural pigmentation. Besides, since the coacervates are insoluble in acid pH of stomach, this undigested lipid is delivered slowly in the intestinal tract, which can help treatment of metabolic disturbs. Accordingly, this study intended to optimize palm oil microencapsulation by complex coacervation using gelatin and gum Arabic as wall materials. For this purpose, the effects of wall material concentration (WM) (2.5, 5.0, and 7.5% w/v), gelatin:gum Arabic ratio (G:GA) (1:2; 1:1; 2:1), and core:wall material ratio (C:WM) (75, 100, and 125%) on the encapsulation efficiency, particle morphology, and size distribution of microcapsules were investigated. Microencapsulation assays followed a factorial central design and, after coacervation, the microcapsules were freeze‐dried. The highest values of encapsulation efficiency were obtained using G:GA = 1:1 or 2:1 with C:WM = 100%, whereas the WM concentration could vary from 2.5 to 7.5%. High concentrations of WM (7.5%) and G:GA = 2:1 hampered the formation of spherical or oval microcapsules. Microcapsules showed average diameter (D[4.3]) between 97 and 690 µm, with increasing concentration of WM and higher C:WM ratio contributing to formation of larger microcapsules. The G:GA ratio showed the highest influence on the particle size, with the 1:2 ratio resulting in smaller microcapsules. Practical applications: Palm oil is a significant source of antioxidants and other phytonutrients, and its microencapsulation may protect these bioactive compounds, enabling its use to nutritional enrichment of dry food formulations, at the same time as functioning as a natural pigment given the intense reddish‐orange color of the oil. In addition, the microcapsules may slow down palm oil release in the gastrointestinal tract, since the coacervates are insoluble in acid pH of stomach, allowing this nutrient to achieve the ileum before being digested and help treatment of metabolic disturbs. Accordingly, microencapsulation of palm oil can be of great interest for food and pharmaceutical industries to develop controlled‐delivery systems to encapsulate and slow down digestion of lipids, inducing modulation of satiety response. [ABSTRACT FROM AUTHOR]

Background Serotonergic system is believed to play a role in levodopa‐induced‐dyskinesias pathogenesis, and serotonin transporter has been evaluated as potential target. Aim of the study To retrospectively investigate the potential effect of selective serotonin reuptake inhibitors (SSRIs) during dopaminergic treatment, in the development of dyskinesias in patients with Parkinson's disease (PD). Methods One hundred and thirty‐five consecutive patients with PD, with 10‐year follow‐up since diagnosis. Age at PD onset, duration of levodopa treatment, maximum daily dose, and SSRIs exposure were collected. Risk, latency, and severity of dyskinesias were evaluated comparing patients with and without SSRIs exposure. Results Forty‐nine patients received SSRIs for a variable period, 86 were never treated; no significant difference between the groups was observed (P = 0.897) in the prevalence of dyskinesias. Considering latency between PD diagnosis and dyskinesias onset, patients exposed to SSRIs developed dyskinesias later (6.48 ± 1.99 vs 5.70 ± 1.89 years, P = 0.020). The median dyskinesia severity score was 0 in the exposed group vs 1 in non‐exposed patients (P = 0.025). Multivariate analysis demonstrated SSRIs exposure as the only independent predictor, protecting from severe dyskinesia. Conclusions Use of SSRIs in patients with PD did not protect from dyskinesias; however, exposure may delay the onset and reduce the severity, confirming modulation of the serotonergic system as possible antidyskinetic strategy. [ABSTRACT FROM AUTHOR]

Introduction: In idiopathic Parkinson’s disease (PD), two different clinical phenotypes are usually distinguished: a tremor dominant variant (TD) and an akinetic-rigid type (ART). TD patients are characterized by a slower disease progression and a minor cognitive impairment. Striatal density of DAT, as quantified by FP-CIT SPECT, has been reported to correlate with rigidity and akinesia but not with tremor. Objective: To evaluate FP-CIT uptake in TD and ART phenotypes. Methods: We retrospectively evaluated from our database the pre-synaptic nigro-striatal function of 24 patients with TD-PD and 38 patients with ART-PD who underwent a FP-CIT SPECT within 1 year from disease onset. Results: Disease duration, age at the time of SPECT scan and disease severity as measured with Unified Parkinson’s Disease Rating scale part III (UPDRS III) were not statistically different between the two groups. Putamen contralateral to the most clinically affected side showed a lower FP-CIT uptake in ART patients compared to TD patients. No statistically significant differences emerged when considering bilateral caudate and ipsilateral putaminal uptake, as well as asymmetry indices and caudate/putamen ratios. FP-CIT contralateral putaminal uptake correlated with the severity of rigidity and hypokinesia but not with tremor. Conclusions: These data suggest that other neurotransmitter systems apart from the nigro-striatal dopaminergic system are involved in the generation of Parkinsonian tremor, and they are consistent with previous evidence of a lack of correlation between tremor severity and FP-CIT uptake. Putaminal relative sparing in TD patients could partially explain the slower disease progression reported in this PD phenotype. [ABSTRACT FROM AUTHOR]

Exposure of immature rat cerebellar granule cell cultures to the type 4 metabotropic glutamate (mGlu4) receptor enhancer N-phenyl-7(hydroxyimino)cyclopropa[b]chromen-la-carboxamide (PHCCC) reduced [³H]thymidine incorporation. Its action was sensitive to the growth conditions and was attenuated by two mGlu4 receptor antagonists. An antiproliferative action of PHCCC was also seen in cultures from wild-type, but not mGlu4, knock-out mice. At least in rat cultures, PHCCC was not neurotoxic and enhanced neuritogenesis. Although PHCCC reduced the increase in cAMP formation and phospho-AKT levels induced by forskolin, none of these transduction pathways significantly contributed to the reduction of [³H]thymidine incorporation. Interestingly, PHCCC reduced the expression of Gli-1, a transcription factor that mediates the mitogenic action of Sonic hedgehog. Finally, we treated newborn rats with PHCCC either intracerebrally (infusion of 5 nmol/2 µl in the cerebellar region once every other day) or systemically (5 mg/kg, i.p., once daily) from postnatal days 3-9. Local infusion of PHCCC induced substantial changes in the morphology of the developing cerebellum. In contrast, systemic injection of PHCCC induced only morphological abnormalities of the cerebellar lobule V, which became visible 11 d after the end of the treatment. These data suggest that mGlu4 receptors are involved in the regulation of cerebellar development. [ABSTRACT FROM AUTHOR]

GFAPβ mRNA is an alternative transcript of the glial fibrillary acidic protein (GFAP) gene, whose transcriptional start site is located 169 nucleotides upstream to the classical GFAPα mRNA. By an RT-PCR method with primers on separate exons, we were able to confirm the presence of GFAP transcripts with a longer 5′ untraslated region in all the examined areas of rat brain and in primary cultures of astroglial cells. Northern blot analysis, using an oligoprobe specific for the 5′ region of GFAPβ, revealed a single hybridization band of 2.9 kb in all the brain regions examined and in primary cultures of astroglial cells. The availability of the quantitative Northern blot assay allowed further studies on the regulation of GFAPβ expression in vivo. Since it is well-known that neuronal brain injury is one of the most powerful inducers of GFAP, we examined the expression of GFAPα and β after a neurotoxic lesion in the rat hippocampus. Results obtained show a parallel increase in both GFAP transcripts with an identical time-course, suggesting that regulatory regions of the gene influence in similar way the rate of transcription at the two different start sites (α and β) or that a similar post-transcriptional mechanism is involved in regulating both mRNA isoforms. [ABSTRACT FROM AUTHOR]

In the present study we analyzed the age-dependent changes of mRNA levels for cytochrome c oxidase and F0F1-ATP synthase subunits in rat cerebral cortex and cerebellum. To establish whether the regulation of expression is transcriptional or post-transcriptional, the results were compared to those related to protein subunits levels, of the same enzymatic complexes, previously observed. The different patterns of age-related changes of mRNA subunits, in particular the lower increments, compared with those related to protein subunits, indicate that post-transcriptional mechanisms of regulation might be involved in the coordinated expression of the various subunits of each complex. Northern blotting analyses of RNA from the cerebellum of rats at the various ages, showed also differences in age-dependent patterns of transcription between cerebral cortex and cerebellum. Moreover, the major age-dependent changes of mitochondrial-encoded subunits, compared with the nuclear-encoded ones, previously observed at proteins level, occur also during transcription. [ABSTRACT FROM AUTHOR]

The contents of subunits I, II/III, and IV of cytochrome c oxidase and of subunits α, β and γ of FoF1 ATP synthase in inner mitochondrial membrane proteins purified from cerebral cortex of rat at 2, 6, 12, 18, 24, and 26 months of age were analyzed by western blot. Age-related changes in the content of subunits, either of mitochondrial or nuclear origin, were observed. All the cytochrome c oxidase (COX) subunits examined showed an age-related increase from 2-month-old rats up to 24 months with a decrease at the oldest age (26 months). The same pattern of age-dependent changes was observed for γ ATP synthase, while the α and β subunits increased progressively up to 26 months. [ABSTRACT FROM AUTHOR]

An increase in astrocyte mitogenic factors and in some specific astroglial enzymatic activities after neuronal injury has been observed. Our study is concerned with the effect of the intracerebral administration of ibotenic acid (IBO) into the rat hippocampus. IBO injection causes a selective degeneration of neurons while sparing afferent fibers. We observed a transient increase in glutamine synthetase activity, a well-known astroglial marker, reaching a peak at 9-15 days after injury in lesioned hippocampus. We investigated the presence of astrocyte mitogenic factors at various times after toxin injection. Crude extracts, prepared from lesioned hippocampi 4, 9, and 14 days after IBO injection, were tested for the ability to stimulate [ methyl-H]thymidine incorporation into rat astroglial cell cultures. Crude extracts prepared 9 and 14 days after IBO injection showed a higher mitogenic activity compared to extracts prepared 4 days after lesion. Mitogenic activity of injured brain extracts was suppressed by heat inactivation (100°C for 10 min). [ABSTRACT FROM AUTHOR]

Background Huntington's disease (HD) is pathologically characterised by a selective neurodegeneration of vulnerable populations of neurons, with an early marked neuronal loss and atrophy in the neostriatum. Dopaminergic innervations of neostriatal neurons originate in the substantia nigra pars compacta. Few studies have investigated the neuronal loss and the functional role of the substantia nigra in HD. Neuropathological and neurochemical studies provide conflicting results, with the evidence of neuronal loss varying from minimal loss to 40%. The few imaging studies evidenced a reduction of striatal DAT uptake and vescicular monoamine transporter type-2 (VMAT2). No correlations with clinical data have yet been investigated. Aims We have evaluated in vivo the integrity of nigrostriatal projections in genetically confirmed HD patients and determined whether their clinical and neuropsychiatric features are correlated with the dopamine transporter (DAT) levels. Methods 12 HD patients and 12 controls, age matched, underwent SPECT scans with 123I-FP-CIT, a tracer that selectively binds to DAT, following an adequate drug washout. The association between clinical aspects (age of onset, duration and severity of disease, mean number of triplets, severity of involuntary movements and bradykinesia), neuropsychological assessment (verbal and visuospatial memory, attentive, executive and abstractive capacities), neuropsychiatric features (NeuroPsychiatry Inventory Scale) and striatal DAT uptake (ROI approach analysis) was explored. Results Striatal (p<0.05), caudate (p<0.05) and putaminal (p<0.01) uptake was significantly lower in patients with respect to controls. No correlation between striatal uptake and clinical or neuropsychological features was found. Conclusions Reduced striatal DAT binding suggests nigrostriatal pathology in HD that could be related to substantia nigra degeneration. The absence of any correlation with age of onset, disease duration and severity and the number of triplets suggests that nigrostriatal pathology occurs early in the course of the disease. Also, the lack of any kind of correlation between clinical, neuropsychological and neuropsychiatric features with striatal DAT uptake suggests that motor and both psychiatric and cognitive aspects in HD are not related to nigrostriatal degeneration. [ABSTRACT FROM PUBLISHER]

Oxidative damage is the major responsible for mitochondrial dysfunction during aging and many neurodegenerative diseases with respiratory chain Complex I mostly affected. A down-regulation of the mitochondrial respiratory chain Complex-I subunits ND1 (mitochondrial encoded) in rat total cerebral cortex RNA and 39 kDa (nuclear encoded) in frontal cortex protein extracts was observed at 6, 12 and 28 months of age. However the 39 kDa subunit showed an age-related up-regulation in the parietal cortex and no changes in the cerebellum protein extracts. In frontal and parietal cortex protein extracts a significant reduction of subunit α (nuclear encoded) of F[sub o]F[sub 1]-ATP synthase, with no changes in the cerebellum, were also observed. A similar impairment was found also for mitochondrial adenine nucleotide translocator ANT-1 in total rat cerebral cortex RNA. Any change of subunit synthesis might lead to neuronal dysfunction and increase of ROS. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the research paper "JAK/STAT Signaling Pathway Is Involved In INOS Induction In Primary Astroglial Cell Culture." Glial cells are induced to synthesize huge amount of NO in response to lipopolysaccharide and cytokines. Signaling transduction pathways for the transcription of the inducible form of NOS is still to be ordained. Trosine phosphorylation in primary astroglial cell culture can reach its maximum at 15 minutes and remains constant until 90 minutes.