Ionic fluctuations in finite volumes: fractional noise and hyperuniformity.

Observing finite regions of a bigger system is a common aim, from microscopy to molecular simulations. In the latter especially, there is ongoing interest in predicting thermodynamic properties from tracking fluctuations in finite observation volumes. However, kinetic properties have received little attention, especially not in ionic solutions, where electrostatic interactions play a decisive role. Here, we probe ionic fluctuations in finite volumes with Brownian dynamics and build an analytical framework that reproduces our simulation results and is broadly applicable to other systems with pairwise interactions. Particle number and charge correlations exhibit a rich phenomenology with time, characterized by a diversity of timescales. The noise spectrum of both quantities decays as 1/f3/2, where f is the frequency. This signature of fractional noise shows the universality of 1/f3/2 scalings when observing diffusing particles in finite domains. The hyperuniform behaviour of charge fluctuations, namely that correlations scale with the area of the observation volume, is preserved in time. Correlations even become proportional to the box perimeter at sufficiently long times. Our results pave the way to understand fluctuations in more complex systems, from nanopores to single-particle electrochemistry.

Electrical noise in electrolytes: a theoretical perspective.

Seemingly unrelated experiments such as electrolyte transport through nanotubes, nano-scale electrochemistry, NMR relaxometry and surface force balance measurements, all probe electrical fluctuations: of the electric current, the charge and polarization, the field gradient (for quadrupolar nuclei) and the coupled mass/charge densities. The fluctuations of such various observables arise from the same underlying microscopic dynamics of the ions and solvent molecules. In principle, the relevant length and time scales of these dynamics are encoded in the dynamic structure factors. However, modelling the latter for frequencies and wavevectors spanning many orders of magnitude remains a great challenge to interpret the experiments in terms of physical processes such as solvation dynamics, diffusion, electrostatic and hydrodynamic interactions between ions, interactions with solid surfaces, etc. Here, we highlight the central role of the charge-charge dynamic structure factor in the fluctuations of electrical observables in electrolytes and offer a unifying perspective over a variety of complementary experiments. We further analyze this quantity in the special case of an aqueous NaCl electrolyte, using simulations with explicit ions and an explicit or implicit solvent. We discuss the ability of the standard Poisson-Nernst-Planck theory to capture the simulation results, and how the predictions can be improved. We finally discuss the contributions of ions and water to the total charge fluctuations. This work illustrates an ongoing effort towards a comprehensive understanding of electrical fluctuations in bulk and confined electrolytes, in order to enable experimentalists to decipher the microscopic properties encoded in the measured electrical noise.

Frequency and field-dependent response of confined electrolytes from Brownian dynamics simulations.

Using Brownian dynamics simulations, we investigate the effects of confinement, adsorption on surfaces, and ion-ion interactions on the response of confined electrolyte solutions to oscillating electric fields in the direction perpendicular to the confining walls. Nonequilibrium simulations allows to characterize the transitions between linear and nonlinear regimes when varying the magnitude and frequency of the applied field, but the linear response, characterized by the frequency-dependent conductivity, is more efficiently predicted from the equilibrium current fluctuations. To that end, we (rederive and) use the Green-Kubo relation appropriate for overdamped dynamics, which differs from the standard one for Newtonian or underdamped Langevin dynamics. This expression highlights the contributions of the underlying Brownian fluctuations and of the interactions of the particles between them and with external potentials. Although already known in the literature, this relation has rarely been used to date, beyond the static limit to determine the effective diffusion coefficient or the DC conductivity. The frequency-dependent conductivity always decays from a bulk-like behavior at high frequency to a vanishing conductivity at low frequency due to the confinement of the charge carriers by the walls. We discuss the characteristic features of the crossover between the two regimes, most importantly how the crossover frequency depends on the confining distance and the salt concentration, and the fact that adsorption on the walls may lead to significant changes both at high and low frequencies. Conversely, our results illustrate the possibility to obtain information on diffusion between walls, charge relaxation, and adsorption by analyzing the frequency-dependent conductivity.

Associations between Prolactin, Diabetes, and Cognitive Impairment: A Literature Review.

BACKGROUND: Converging evidence indicates prolactin (PRL) and diabetes play an important role in the pathophysiology of cognitive impairment. However, little is known about the mechanisms responsible for the effects of PRL and diabetes on cognitive impairment. SUMMARY: We summarize and review the available literature and current knowledge of the association between PRL and diabetes on aspects of cognitive impairment. KEY MESSAGES: The phosphatidylinositol 3-kinase/protein kinase B pathway is central to the molecular mechanisms underlying how PRL and diabetes interact in cognitive impairment. Further work is needed to identify the interaction between PRL and diabetes, especially in the molecular aspects of cognitive impairment, which can suggest novel strategies for cognitive dysfunction treatment.

Association between Serum Prolactin Levels and Neurodegenerative Diseases: Systematic Review and Meta-Analysis.

INTRODUCTION: Prolactin (PRL) exerts inflammatory and anti-inflammatory properties and is also thought to play an important role in the pathogenesis of neurodegenerative diseases (NDs). However, serum PRL levels in patients with NDs were inconsistent in the research literature. OBJECTIVE: We aimed to assess the serum PRL levels in patients with NDs. METHODS: Electronic databases, including MEDLINE, Embase, Cochrane Library database, clinicaltrials.gov, Web of Science, and Google Scholar, and reference lists of articles were searched up to December 31, 2020. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. RESULTS: A total of 36 comparisons out of 29 studies (3 RCTs and 26 case controls) focusing on NDs (including Parkinson's disease, Alzheimer's disease, Huntington's disease [HD], multiple sclerosis [MS], and epilepsy) were reported. The meta-analysis showed that there was no statistically significant difference in serum PRL levels between patients with NDs and healthy controls (SMD = 0.40, 95% CI: -0.16 to 0.96, p = 0.16). Subgroup analysis showed that serum PRL levels in patients with HD and MS were higher than those of healthy controls. Furthermore, patients with NDs aged <45 years had higher serum PRL levels (SMD = 0.97, 95% CI: 0.16-1.78, p = 0.018) than healthy controls. High serum PRL levels were found in subgroups such as the microenzymatic method, Asia, and the Americas. CONCLUSIONS: Our meta-analysis showed serum PRL levels in patients with HD and MS were significantly higher than those in healthy controls. Serum PRL levels were associated with age, region, and detection method. Other larger sample studies using more uniform detection methods are necessary to confirm our results.

Associations among the TREM-1 Pathway, Tau Hyperphosphorylation, Prolactin Expression, and Metformin in Diabetes Mice.

INTRODUCTION: Diabetes mellitus (DM) is a risk factor for Alzheimer's disease (AD). Increasing evidence indicates that the triggering receptor expressed on myeloid cells (TREM)-1 amplifies chronic inflammation, as well as the roles of prolactin (PRL) and metformin (MET) in tau hyperphosphorylation. However, the associations among TREM-1, tau hyperphosphorylation, PRL expression, and MET in DM remain unclear. METHODS: Streptozotocin was used to induce experimental DM in C57BL/6N mice. MET was orally administered at a dose of 400 mg/kg body weight for 6 weeks prior to hippocampal collection in DM mice. Various parameters pertaining to the TREM-1 pathway, tau hyperphosphorylation, PRL, and related factors were analyzed. RESULTS: Quantitative polymerase chain reaction and Western blot analysis demonstrated that the expression levels of TREM-1, DAP12, casp1, interleukin-1ß, Cox2, inducible nitric oxide synthase, pituitary transcriptional factor-1 (Pit-1), and PRL were significantly increased in the hippocampus of DM mice; the expression levels of these pro-inflammatory mediators, PRL receptor (PRLR) short or long (PRLR-S and PRLR-L), and PRL regulatory element-binding (Preb) protein in DM mice treated with MET (DM + MET) were significantly decreased compared with those in control (CON) mice. The levels of p-Tau and glycogen synthase kinase-3 in the DM group were significantly higher than those in the CON group and significantly lower than those in the DM + MET group. CONCLUSION: We confirmed the therapeutic potential of MET for both DM and neurodegeneration. Our findings shed new light on the effects of DM on the pathophysiology of AD via the TREM-1 pathway and PRL expression. Thus, an improved understanding of the TREM-1 pathway in hyperglycemic conditions, as well as PRL, Preb, Pit-1, PRLR-L, and PRLR-S gene expression in the liver, brain, and other sites, may help unravel the pathogenesis of insulin resistance and neurodegeneration.

Role of prolactin in the protective effect of amisulpride against 1,2-Diacetylbenzene's neurotoxicity.

Exposure to organic solvents is associated with various health problems, including neurodegenerative diseases. Among these solvents, 1,2-diethylbenzene is notable for its ability to produce a toxic metabolite, 1,2-Diacetylbenzene (DAB), which can cause memory impairment. Prolactin (PRL) is theorized to protect the central nervous system. Certain antipsychotic drugs, known for increasing PRL secretion, have shown to improve cognitive performance in psychotic Alzheimer's patients. Among these, amisulpride stands out for its high efficacy, limited side effects, and high selectivity for dopamine D2 receptors. In our study, we explored the potential of amisulpride to inhibit DAB-induced neurotoxicity via PRL activation. Our results show that amisulpride enhances the PRL/JAK/STAT, PI3K/AKT, and BDNF/ERK/CREB pathways, playing critical roles in PRL's neuroprotection pathways and memory formation. Additionally, amisulpride inhibited DAB-triggered NLRP3 inflammasome activation and apoptosis. Collectively, these findings suggest that amisulpride may be a promising therapeutic intervention for DAB-induced neurotoxicity, partly through activating the PRL pathway.

Protective effect of Prolactin releasing peptide against 1,2-diacetylbenzene -induced neuroinflammation.

Prolactin-releasing peptide (PrRP) has been investigated as a potential therapeutic for diabetes by the effect of food intake reduction, increasing leptin signaling, and insulin tolerance. Recent studies focused on its synaptogenesis and protective effects against neurodegeneration. Whereas 1,2-diacetylbenzene (DAB), a common metabolite of a neurotoxicant 1,2-diethyl benzene, causes memory impairment and neurotoxicity partly through the inflammatory process. Our present study assessed the effect of PrRP in microglia and its action in balancing the inflammation to protect against DAB. We observed that PrRP modulated NADPH oxidase - regulated NLRP3 inflammasome and PRL signaling pathways differently between physical and toxic conditions in microglia.

Age-Dependent Sensitivity to the Neurotoxic Environmental Metabolite, 1,2-Diacetylbenzene.

1,2-Diacetylbenzene (DAB) is a metabolite of 1,2-diethylbenzene, which is commonly used in the manufacture of plastics and gasoline. We examined the neurotoxic effects of DAB in young and old rats, particularly its effects on hippocampus. Previously, we reported DAB impairs hippocampal neurogenesis but that the underlying mechanism remained unclear. In this study, we evaluate the toxicities exhibited by DAB in the hippocampi of 6-month-old (young) and 20-month-old (old) male SD rats by treating animals intraperitoneally with DAB at 3 mg/kg/day for 1 week. Hippocampal areas were dissected from brains and RNA was extracted and subjected to RNA-seq analysis. RNA results showed animals exhibited age-dependent sensitivity to the neurotoxic effects of DAB. We observed that inflammatory pathways were up-regulated in old rats but that metabolism- and detoxification-related pathways were up-regulated in young rats. This result in old rats, especially upregulation of the TREM1 signaling pathway (an inflammatory response involved in Alzheimer's disease (AD)) was confirmed by RT-PCR. Our study results provide a better understanding of age-dependent responses to DAB and new insight into the association between DAB and AD.