In vivo imaging of brain androgen receptors in rats: a [18F]FDHT PET study

AbstractIntroductionSteroid hormones like androgens play an important role in the development and maintenance of several brain functions. Androgens can act through androgen receptors (AR) in the brain. This study aims to demonstrate the feasibility of positron emission tomography (PET) with 16β-[18F]fluoro-5α-dihydrotestosterone ([18F]FDHT) to image AR expression in the brain.MethodsMale Wistar rats were either orchiectomized to inhibit endogenous androgen production or underwent sham-surgery. Fifteen days after surgery, rats were subjected to a 90-min dynamic [18F]FDHT PET scan with arterial blood sampling. In a subset of orchiectomized rats, 1mg/kg dihydrotestosterone was co-injected with the tracer in order to saturate the AR. Plasma samples were analyzed for the presence of radioactive metabolites by radio-TLC. Pharmacokinetic modeling was performed to quantify brain kinetics of the tracer. After the PET scan, the animals were terminated for ex-vivo biodistribution.ResultsPET imaging and ex vivo biodistribution studies showed low [18F]FDHT uptake in all brain regions, except pituitary. [18F]FDHT uptake in the surrounding cranial bones was high and increased over time. [18F]FDHT was rapidly metabolized in rats. Metabolism was significantly faster in orchiectomized rats than in sham-orchiectomized rats. Quantitative analysis of PET data indicated substantial spill-over of activity from cranial bones into peripheral brain regions, which prevented further analysis of peripheral brain regions. Logan graphical analysis and kinetic modeling using 1- and 2-tissue compartment models showed reversible and homogenously distributed tracer uptake in central brain regions. [18F]FDHT uptake in the brain could not be blocked by endogenous androgens or administration of dihydrotestosterone.ConclusionThe results of this study indicate that imaging of AR availability in rat brain with [18F]FDHT PET is not feasible. The low AR expression in the brain, the rapid metabolism of [18F]FDHT in rats and the poor brain penetration of the tracer likely contributed to the poor performance of [18F]FDHT PET in this study

Ovariectomy-induced depressive-like behavior and brain glucose metabolism changes in female rats are not affected by chronic mild stress

The increased incidence of depression in women going through peri-menopause suggests that fluctuations in estrogen levels may increase the risk of developing depression. Nonetheless, this psychiatric disorder is likely to be multifactorial and consequently an additional trigger may be needed to induce depression in this population. Stress could be such a trigger. We therefore investigated the effect of ovarian estrogen depletion and chronic mild stress (CMS) on depressive-like behavior and brain metabolism in female rats. Approximately 2 and 9 weeks after estrogen depletion by ovariectomy, behavioral changes were assessed in the open-field test and the forced swim test, and brain metabolism was measured with [18F]FDG PET imaging. A subset of animals was subjected to a 6-weeks CMS protocol starting 17 days after ovariectomy. Short-term estrogen depletion had a significant effect on brain metabolism in subcortical areas, but not on behavior. Differences in depressive-like behavior were only found after prolonged estrogen depletion, leading to an increased immobility time in the forced swim test. Prolonged estrogen depletion also resulted in an increase in glucose metabolism in frontal cortical areas and hippocampus, whereas a decrease glucose metabolism was found in temporal cortical areas, hypothalamus and brainstem. Neither short-term nor prolonged estrogen depletion caused anxiety-like behavior. Changes in body weight, behavior and brain glucose metabolism were not significantly affected by CMS. In conclusion, ovarian estrogen depletion resulted in changes in brain metabolism and depressive-like behavior, but these changes were not enhanced by CMS

Principles and philosophies for speech and language therapists working with people with primary progressive aphasia: An international expert consensus

Purpose: Primary progressive aphasia (PPA) is a language-led dementia associated with Alzheimer’s pathology and fronto-temporal lobar degeneration. Multiple tailored speech and language interventions have been developed for people with PPA. Speech and language therapists/speech-language pathologists (SLT/Ps) report lacking confidence in identifying the most pertinent interventions options relevant to their clients living with PPA during their illness trajectory. Materials and methods: The aim of this study was to establish a consensus amongst 15 clinical-academic SLT/Ps on best practice in selection and delivery of speech and language therapy interventions for people with PPA. An online nominal group technique (NGT) and consequent focus group session were held. NGT rankings were aggregated and focus groups video recorded, transcribed, and reflexive thematic analysis undertaken. Results: The results of the NGT identified 17 items. Two main themes and seven further subthemes were identified in the focus groups. The main themes comprised (1) philosophy of person-centredness and (2) complexity. The seven subthemes were knowing people deeply, preventing disasters, practical issues, professional development, connectedness, barriers and limitations, and peer support and mentoring towards a shared understanding. Conclusions: This study describes the philosophy of expert practice and outlines a set of best practice principles when working with people with PPA.Implications for rehabilitation Primary progressive aphasia (PPA) describes a group of language led dementias which deteriorate inexorably over time. Providing speech and language therapy for people with PPA is complex and must be person centred and bespoke. This study describes the philosophy of expert practice and outlines a set of best practice principles for speech and language therapists/pathologists working with people with people with PPA

Interlayer hydrogen-bonded covalent organic frameworks as high-performance supercapacitors

Covalent organic frameworks (COFs) have emerged as promising electrode materials in supercapacitors (SCs). However, their insoluble powder like nature, poor capacitive performance in pristine form, integrated with inferior electrochemical stability is a primary concern for their long-term use in electrochemical-devices. Keeping this in perspective, herein, we report a redox active and hydrogen bonded COF with ultrahigh stability in conc. H2SO4 (18 M), conc. HCl (12 M) and NaOH (9 M). The as-synthesized COF fabricated as thin sheets were efficiently employed as a free-standing supercapacitor electrode material using 3 M aq. H2SO4 as an electrolyte. Moreover, the pristine COF sheet showcased outstanding areal capacitance 1600 mFcm-2 (gravimetric 169 Fg-1) and excellent cyclic stability (> 1,00,000) without compromising its capacitive performance or coulombic efficiency. Moreover, as a proof-of-concept, a solidstate supercapacitor device was also assembled and subsequently tested

Speech and language therapy approaches to managing primary progressive aphasia

The term primary progressive aphasia (PPA) describes a group of neurodegenerative disorders with predominant speech and language dysfunction as their main feature. There are three main variants – the semantic variant, the nonfluent or agrammatic variant and the logopenic variant – each with specific linguistic deficits and different neuroanatomical involvement. There are currently no curative treatments or symptomatic pharmacological therapies. However, speech and language therapists have developed several impairment-based interventions and compensatory strategies for use in the clinic. Unfortunately, multiple barriers still need to be overcome to improve access to care for people with PPA, including increasing awareness among referring clinicians, improving training of speech and language therapists and developing evidence-based guidelines for therapeutic interventions. This review highlights this inequity and the reasons why neurologists should refer people with PPA to speech and language therapists

Assessment of drinking water quality in Bangalore south central zone, Karnataka, India

Waterof good drinking quality is of basic importance to human physiology, and man's continued existence depends very much on its availability. The concentrations of most of the investigated parameters in the drinking water samples from Bangalore south central zone were within the permissible limits of drinking water quality standards and guidelines. The samples S1, S4, S10, S12 and S15 have electrical conductivity above the limit