scholarly journals GPR39 Localization in Aging Human Brain and Correlation of Expression and Polymorphism with Vascular Cognitive Impairment

2021 ◽  
Author(s):  
Catherine Davis ◽  
Theirno Bah ◽  
Wenri Zhang ◽  
Jonathan Nelson ◽  
Kirsti Golgotiu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Neurological Disorders ◽  
Dorsolateral Prefrontal Cortex ◽  
Immunohistochemical Analysis ◽  
Vascular Cognitive Impairment ◽  
Postmortem Brain ◽  
White Matter Hyperintensity ◽  
Dorsolateral Prefrontal ◽  
And Control ◽  
G Protein Coupled

INTRODUCTION: The pathogenesis of vascular cognitive impairment (VCI) is not fully understood. GPR39, an orphan G-protein coupled receptor, is implicated in neurological disorders but its role in VCI is unknown. METHODS: We performed GPR39 immunohistochemical analysis in postmortem brain samples from mild cognitive impairment (MCI) and control subjects. DNA was analyzed for GPR39 SNPs, and correlated with white matter hyperintensity (WMH) burden on premortem MRI. RESULTS: GPR39 is expressed in aged human dorsolateral prefrontal cortex, localized to microglia and peri-capillary cells resembling pericytes. GPR39-capillary colocalization, and density of GPR39-expressing microglia was increased in aged brains compared to young. SNP distribution was equivalent between groups; however, homozygous SNP carriers were present only in the MCI group, and had higher WMH volume than WT or heterozygous SNP carriers. DISCUSSION: GPR39 may play a role in aging-related VCI, and may serve as a therapeutic target and biomarker for the risk of developing VCI.

scholarly journals Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e040466
Author(s):  
Aravind Ganesh ◽  
Philip Barber ◽  
Sandra E Black ◽  
Dale Corbett ◽  
Thalia S Field ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Vascular Cognitive Impairment ◽  
White Matter Injury ◽  
White Matter Hyperintensity ◽  
Limb Ischaemia ◽  
Ischaemic Brain

IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60–85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13–24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and disseminationResearch Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration numberNCT04109963.

Stimulation of the dorsolateral-prefrontal cortex improves working memory and planning

2021 ◽  
Vol 25 (1) ◽  
pp. 1-17
Author(s):  
Puladi Farzaneh ◽  
Bagheri Masood ◽  
Ghasem Askarizadeh ◽  
Afsaneh Moradi
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Response Time ◽  
Dorsolateral Prefrontal Cortex ◽  
Control Group ◽  
Response Accuracy ◽  
Significant Difference ◽  
Dorsolateral Prefrontal ◽  
The Right ◽  
And Control

The present study aimed to investigate whether working memory (WM) and planning performances can be enhanced using transcranial direct current stimulation (tDCS). A total of 30 healthy individuals were randomly assigned to two groups: active (A)-tDCS and control (S)-tDCS. Anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC) (F3) and cathodal stimulation over the right orbitofrontal cortex (OFC) (FP2) were further implemented at 2 mA in the A-tDCS group, while there was no intervention in the control group. The tools used were software versions of the three-level n-back task and Tower of London (TOL) task, and for each task we measured participants’ response accuracy and response time. The results showed a significant difference between the groups in both cognitive functions, suggesting that tDCS can improve response accuracy in memory and problem-solving ability, but it is less effective in terms of improving response time on planning. Overall, findings suggest that tDCS can enhance WM and planning performances.

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