The impact of gamma transcranial alternating current stimulation (tACS) on cognitive and memory processes in patients with mild cognitive impairment or Alzheimer's disease: A literature review.

BACKGROUND: Transcranial alternating current stimulation (tACS)-a noninvasive brain stimulation technique that modulates cortical oscillations through entrainment-has been demonstrated to alter oscillatory activity and enhance cognition in healthy adults. TACS is being explored as a tool to improve cognition and memory in patient populations with mild cognitive impairment (MCI) and Alzheimer's disease (AD). OBJECTIVE: To review the growing body of literature and current findings obtained from the application of tACS in patients with MCI or AD, highlighting the effects of gamma tACS on brain function, memory, and cognition. Evidence on the use of brain stimulation in animal models of AD is also discussed. Important parameters of stimulation are underscored for consideration in protocols that aim to apply tACS as a therapeutic tool in patients with MCI/AD. FINDINGS: The application of gamma tACS has shown promising results in the improvement of cognitive and memory processes that are impacted in patients with MCI/AD. These data demonstrate the potential for tACS as an interventional stand-alone tool or alongside pharmacological and/or other behavioral interventions in MCI/AD. CONCLUSIONS: While the use of tACS in MCI/AD has evidenced encouraging results, the effects of this stimulation technique on brain function and pathophysiology in MCI/AD remains to be fully determined. This review explores the literature and highlights the need for continued research on tACS as a tool to alter the course of the disease by reinstating oscillatory activity, improving cognitive and memory processing, delaying disease progression, and remediating cognitive abilities in patients with MCI/AD.

Heterokaryon myotubes with normal mouse and Duchenne nuclei exhibit sarcolemmal dystrophin staining and efficient intracellular free calcium control.

Duchenne and mdx muscle tissues lack dystrophin where it normally interacts with glycoproteins in the sarcolemma. Intracellular free calcium ([Ca2+]i) is elevated in Duchenne and mdx myotubes and is correlated with abnormally active calcium-specific leak channels in dystrophic myotubes. We fused Duchenne human and normal mouse myoblasts and identified heterokaryon myotubes by Hoechst 33342 staining to measure the degree to which dystrophin introduced by normal nuclei could incorporate throughout the myotube at the sarcolemma and restore normal calcium homeostasis. Dystrophin expression in myotubes was determined by immunofluorescence and confocal laser scanning microscopy. Dystrophin was expressed at the sarcolemma in normal mouse and heterokaryon myotubes, but not in Duchenne myotubes. In heterokaryons, extensive dystrophin localization occurred at the sarcolemma even where only Duchenne nuclei were present, indicating that dystrophin does not exhibit nuclear domains. Heterokaryon, normal mouse and Duchenne myotube [Ca2+]i was measured using fura-2 and fluorescence ratio imaging. Heterokaryon and normal mouse myotubes were found to maintain similar levels of [Ca2+]i. In contrast, Duchenne myotubes had significantly higher [Ca2+]i (p < 0.001). Furthermore, the ability of heterokaryons to maintain normal [Ca2+]i did not depend on greater numbers of normal nuclei than Duchenne being present in the myotube. These results support the view that dystrophin expression in heterokaryons allows for efficient control of [Ca2+]i.

Angiotensin and converting enzyme regulate extrarenal salt excretion in ducks.

Numerous previous studies have proposed a salt-conserving role for the renin-angiotensin system in mammals, but there is little evidence of this putative role in birds. Especially interesting are marine birds, which have a relatively limited ability to regulate the osmolality and ionic composition of their urine but possess extrarenal salt glands capable of excreting a highly concentrated NaCl solution. In the present experiments, hypertonic saline, angiotensin I (ANG I), and captopril were infused iv into chronically cannulated ducks to study the neuroendocrine, cardiovascular, renal, and extrarenal excretory responses to osmotic stress. Infusion of hypertonic saline elicited nasal salt excretion, which could be stopped completely by coadministration of ANG I. The effective dose of ANG I increased the plasma norepinephrine (NE) concentration, but did not alter heart rate or arterial blood pressure. Captopril enhanced extrarenal salt excretion in the saline-loaded ducks. The converting enzyme inhibitor also blocked the noradrenergic and NaCl-retaining actions of ANG I; conversely, coadministration of captopril and ANG I increased the plasma epinephrine (E) concentration. These findings indicate that the renin-angiotensin system, in addition to effects on the sympathoadrenal system, regulates NaCl and water metabolism in birds with extrarenal salt glands.

Catecholamine hormones and the control of avian salt glands.

Hypertonic saline loading (0.5 M NaCl, 15 ml.kg-1 i.v.) increased cardiac frequency and elicited nasal salt gland secretion in control ducks. Partial depletion of catecholamines by prior treatment with reserpine decreased body weight, lowered arterial pressure and abolished the tachycardiac responses to saline loading. Reserpine also increased plasma concentrations of Na, K and total osmolytes, yet altered neither the composition nor the flow rate of nasal fluid secretion. The preservation of the normal secretory responses to hypertonic stress in hypotensive, reserpine-treated ducks indicates that the nasal salt glands can function independently of changes in circulating catecholamine hormones.

Formation of vesicles by the action of acyl-CoA:1-acyllsophosphatidylcholine acyltransferase from rat liver microsomes: optimal solubilization conditions and analysis of lipid composition and enzyme activity.

The enzyme acyl coenzyme A:1-acyllysophosphatidylcholine acyltransferase (acyl-CoA:lysoPC acyltransferase) can be isolated in newly formed phosphatidylcholine (PC) vesicles by solubilization of rat liver microsomes with the two substrates lysoPC and acyl-CoA. In this study, we sought to optimized the conditions for the formation of PC vesicles and analyzed the lipid composition and enzyme activity of the newly formed vesicles. Analysis of PC vesicles formed by incubation of the microsomal preparation with 1-(C16:0)lysoPC and C18:1CoA, C18:2CoA, or C20:4CoA showed that the optimal protein:lysoPC ratio was 1:5 (by weight) and the optimal lysoPC:acyl-CoA ratio was 1:1 (molar amounts). PC formation increased with incubation time; after 20 h of incubation at 37 degrees C, approximately 75% of the lysoPC was converted to PC in the incubation mixture. The phospholipid molecular species composition of the vesicles reflected almost exclusively the substrates used; the vesicles contained approximately 33% of the total acyl-CoA:lysoPC acyltransferase activity from the microsomes and demonstrated a single protein band with a molecular mass of 21 kDa by gel electrophoresis. The procedure selected for the enzyme specific for lysoPC acylation, as enzyme activity toward lysophosphatidylethanolamine (lysoPE), lysophosphatidylserine (lysoPS), and lysophosphatidylinositol (lysoPI), was very low. In addition, the utilization of different acyl-CoA substrates for acylation of lysoPC was different from that in microsomes. These results show that an enzyme specific for the formation of PC from lysoPC can be isolated in PC vesicles with a designed phospholipid molecular species composition and that the lipid environment plays an important role in the regulation of the enzyme's affinity for its substrates.