Effect of nutritional supports on malnutrition, cognition, function and biomarkers of Alzheimer's disease: a systematic review.

AIM: To summarize the nutritional supplementation on biochemical parameters, cognition, function, Alzheimer's Disease (AD) biomarkers and nutritional status. MATERIALS AND METHODS: PubMed, Web of Science, Korean Journal Database, Russian Science Citation Index, SciELO Citation Index, Cochrane Library and Scopus databases were searched until 16 April 2021. 22.193 records in total were reached according to inclusion and exclusion criteria. Included Studies were evaluated through the Modified Jadad Scale and gathered under four subheadings. RESULTS: Forty-eight studies with a total of 7009 AD patients were included. Souvenaid, ONS (368 ± 69 kcal), Vegenat-med, 500 mg Resveratrol, ONS (200 mL) were effective nutritional supplements on promoting weight gain and protecting malnutrition status but showed conflicting results in Body mass index, Mid-Upper-Arm Circumference and Triceps Skin Fold Thickness. ONS and a lyophilized whole supplementation Vegenat-med intake made an increase in MNA scores. While all nutritional supplements showed controversial results in biochemical parameters but caused a decrease in Hcy levels which caused reductions in brain Aß plaque (increase serum Aß), p-Tau and cognitive improvement. Folic acid and vitamin D decreased serum APP, BACE1, BACE1mRNA. Resveratrol, Hericium erinaceus mycelia, vitamin D and Betaine supplements improved cognitive, functional prognosis and quality of life unlike other nutritional supplements had no effect on cognitive scales. CONCLUSIONS: Better designed trials with holistic measures are needed to investigate the effect of nutritional support on the AD biomarkers, cognitive status, biochemical parameters and functional states. Also, more beneficial results can be obtained by examining the simultaneous effects of nutritional supplements with larger sample groups.

Quetiapine improves sensorimotor gating deficit in a sleep deprivation-induced rat model.

Background: Sleep deprivation (SD) impairs pre-stimulus inhibition, but the effect of quetiapine (QET) remains largely unknown. Objective: This study aimed to investigate the behavioral and cognitive effects of QET in both naïve and sleep-deprived rats. Materials and methods: Seven groups (n = 49) of male Wistar Albino rats were used in this study. SD was performed using the modified multiple platform technique in a water tank for 72 h. Our study consists of two experiments investigating the effect of QET on pre-pulse inhibition (PPI) of the acoustic startle reflex. The first experiment tested the effect of short- and long-term administration of QET on PPI response in non-sleeping (NSD) rats. The second experiment used 72 h REM sleep deprivation as a model for SD-induced impairment of the PPI response. Here, we tested the effect of QET on the % PPI of SD rats by short- and long-term intraperitoneal injection at the last 90 min of sleep SD and immediately subsequently tested for PPI. Results: 72 h SD impaired PPI, reduced startle amplitude, and attenuated the PPI% at + 4 dB, + 8 dB, and + 16 dB prepulse intensities. 10 mg/kg short and long-term QET administration completely improved sensorimotor gating deficit, increased startle amplitude, and restored the impaired PPI% at + 4 dB, + 8 dB, and + 16 dB after 72 h SD in rats. Conclusion: Our results showed short- and long-term administration of QET improved sensorimotor gating deficit in 72 h SD. Further research is required for the etiology of insomnia and the dose-related behavioral effects of QET.

Targeting the blood-brain barrier disruption in hypertension by ALK5/TGF-Β type I receptor inhibitor SB-431542 and dynamin inhibitor dynasore.

INTRODUCTION: In this study, we aimed to target two molecules, transforming growth factor-beta (TGF-ß) and dynamin to explore their roles in blood-brain barrier (BBB) disruption in hypertension. METHODS: For this purpose, angiotensin (ANG) II-induced hypertensive mice were treated with SB-431542, an inhibitor of the ALK5/TGF-ß type I receptor, and dynasore, an inhibitor of dynamin. Albumin-Alexa fluor 594 was used to assess BBB permeability. The alterations in the expression of claudin-5, caveolin (Cav)-1, glucose transporter (Glut)-1, and SMAD4 in the cerebral cortex and the hippocampus were evaluated by quantification of immunofluorescence staining intensity. RESULTS: ANG II infusion increased BBB permeability to albumin-Alexa fluor 594 which was reduced by SB-431542 (P < 0.01), but not by dynasore. In hypertensive animals treated with dynasore, claudin-5 immunofluorescence intensity increased in the cerebral cortex and hippocampus while it decreased in the cerebral cortex of SB-431542 treated hypertensive mice (P < 0.01). Both dynasore and SB-431542 prevented the increased Cav-1 immunofluorescence intensity in the cerebral cortex and hippocampus of hypertensive animals (P < 0.01). SB-431542 and dynasore decreased Glut-1 immunofluorescence intensity in the cerebral cortex and hippocampus of mice receiving ANG II (P < 0.01). SB-431542 increased SMAD4 immunofluorescence intensity in the cerebral cortex of hypertensive animals, while in the hippocampus a significant decrease was noted by both SB-431542 and dynasore (P < 0.01). CONCLUSION: Our data suggest that inhibition of the TGFß type I receptor prevents BBB disruption under hypertensive conditions. These results emphasize the therapeutic potential of targeting TGFß signaling as a novel treatment modality to protect the brain of hypertensive patients.

Blood-brain barrier targeted delivery of lacosamide-conjugated gold nanoparticles: Improving outcomes in absence seizures.

OBJECTIVE: Most currently available antiepileptics are not fully effective in the prevention of seizures in absence epilepsy owing to the presence of blood-brain barrier (BBB). We aimed to test whether binding an antiepileptic drug, lacosamide (LCM), to glucose-coated gold nanoparticles (GNPs) enables efficient brain drug delivery to suppress the epileptic activity in WAG/Rij rats with absence epilepsy. METHODS: In these animals, intracranial-EEG recording, behavioral test, in vivo imaging of LCM and LCM-GNP conjugate distribution in the brain, inductively coupled plasma mass spectrometry analysis, immunofluorescence staining of glucose transporter (Glut)- 1, glial fibrillary acidic protein (GFAP), and p-glycoprotein (P-gp) and electron microscopy were performed. RESULTS: Lacosamide-GNP conjugates decreased the amplitude and frequency of spike-wave-like discharges (SWDs) and alleviated the anxiety-like behavior as assessed by EEG and elevated plus-maze test, respectively (p < 0.01). The in vivo imaging system results showed higher levels of fluorescein dye tagged to LCM-GNP in the brain during the 5-day injection period (p < 0.01). Immunofluorescence staining displayed decreased P-gp, Glut-1, and GFAP expression by LCM-GNP conjugate treatment predominantly in the cerebral cortex suggesting a potential functionality of this brain region in the modulation of neuronal activity in our experimental setting (p < 0.01). SIGNIFICANCE: We suggest that the conjugation of LCM to GNPs may provide a novel approach for efficient brain drug delivery in light of the effectiveness of our strategy not only in suppressing the seizure activity but also in decreasing the need to use high dosages of the antiepileptics to reduce the frequently encountered side effects in drug-resistant epilepsy.

Targeted delivery of lacosamide-conjugated gold nanoparticles into the brain in temporal lobe epilepsy in rats.

Temporal lobe epilepsy (TLE) is the most common form of epilepsy with focal seizures, and currently available drugs may fail to provide a thorough treatment of the patients. The present study demonstrates the utility of glucose-coated gold nanoparticles (GNPs) as selective carriers of an antiepileptic drug, lacosamide (LCM), in developing a strategy to cross the blood-brain barrier to overcome drug resistance. Intravenous administration of LCM-loaded GNPs to epileptic animals yielded significantly higher nanoparticle levels in the hippocampus compared to the nanoparticle administration to intact animals. The amplitude and frequency of EEG-waves in both ictal and interictal stages decreased significantly after LCM-GNP administration to animals with TLE, while a decrease in the number of seizures was also observed though statistically insignificant. In these animals, malondialdehyde was unaffected, and glutathione levels were lower in the hippocampus compared to sham. Ultrastructurally, LCM-GNPs were observed in the brain parenchyma after intravenous injection to animals with TLE. We conclude that glucose-coated GNPs can be efficient in transferring effective doses of LCM into the brain enabling elimination of the need to administer high doses of the drug, and hence, may represent a new approach in the treatment of drug-resistant TLE.