Exploring Cannabinoids with Enhanced Binding Affinity for Targeting the Expanded Endocannabinoid System: A Promising Therapeutic Strategy for Alzheimer's Disease Treatment.

Despite decades of rigorous research and numerous clinical trials, Alzheimer's disease (AD) stands as a notable healthcare challenge of this century, with effective therapeutic solutions remaining elusive. Recently, the endocannabinoid system (ECS) has emerged as an essential therapeutic target due to its regulatory role in different physiological processes, such as neuroprotection, modulation of inflammation, and synaptic plasticity. This aligns with previous research showing that cannabinoid receptor ligands have the potential to trigger the functional structure of neuronal and brain networks, potentially impacting memory processing. Therefore, our study aims to assess the effects of prolonged, intermittent exposure (over 90 days) to JWH-133 (0.2 mg/kg) and an EU-GMP certified Cannabis sativa L. (Cannabixir® Medium Flos, 2.5 mg/kg) on recognition memory, as well as their influence on brain metabolism and modulation of the expanded endocannabinoid system in APP/PS1 mice. Chronic therapy with cannabinoid receptor ligands resulted in reduced anxiety-like behavior and partially reversed the cognitive deficits. Additionally, a reduction was observed in both the number and size of Aß plaque deposits, along with decreased cerebral glucose metabolism, as well as a decline in the expression of mTOR and CB2 receptors. Furthermore, the study revealed enlarged astrocytes and enhanced expression of M1 mAChR in mice subjected to cannabinoid treatment. Our findings highlight the pivotal involvement of the extended endocannabinoid system in cognitive decline and pathological aspects associated with AD, presenting essential preclinical evidence to support the continued exploration and assessment of cannabinoid receptor ligands for AD treatment.

Inflammasome Molecular Insights in Autoimmune Diseases.

Autoimmune diseases (AIDs) emerge due to an irregular immune response towards self- and non-self-antigens. Inflammation commonly accompanies these conditions, with inflammatory factors and inflammasomes playing pivotal roles in their progression. Key concepts in molecular biology, inflammation, and molecular mimicry are crucial to understanding AID development. Exposure to foreign antigens can cause inflammation, potentially leading to AIDs through molecular mimicry triggered by cross-reactive epitopes. Molecular mimicry emerges as a key mechanism by which infectious or chemical agents trigger autoimmunity. In certain susceptible individuals, autoreactive T or B cells may be activated by a foreign antigen due to resemblances between foreign and self-peptides. Chronic inflammation, typically driven by abnormal immune responses, is strongly associated with AID pathogenesis. Inflammasomes, which are vital cytosolic multiprotein complexes assembled in response to infections and stress, are crucial to activating inflammatory processes in macrophages. Chronic inflammation, characterized by prolonged tissue injury and repair cycles, can significantly damage tissues, thereby increasing the risk of AIDs. Inhibiting inflammasomes, particularly in autoinflammatory disorders, has garnered significant interest, with pharmaceutical advancements targeting cytokines and inflammasomes showing promise in AID management.

Validity and reliability of the Romanian version of the Hill-Bone compliance to high blood pressure therapy scale.

Romania is considered a country with high cardiovascular risk, arterial hypertension and its complications accounting for about 60% of total deaths. The management of high blood pressure often involves a combination of both therapeutic regimens as well as lifestyle changes, to which patients have to be adherent. In order to assess patients adherence to professionals' recommendations, validated tools are needed. The aim of our study was to translate, culturally adapt and validate the Hill-Bone Compliance to High Blood Pressure Therapy Scale into Romanian. The study included 215 participants from Iasi, North-Eastern Romania. The internal consistency of the instrument was measured with Cronbach's alpha coefficient, while the construct validity was determined using exploratory factor analysis and principal component extraction with promax rotation. Sampling adequacy and appropriateness of data for factor analysis was measured using Kaiser-Meyer-Olkin (KMO) statistics and Bartlett's test of sphericity. Our statistical analysis revealed a Cronbach's alpha coefficient of 0.733 (73.3%) and a Kaiser-Meyer-Olkin (KMO) Measure of Sampling Adequacy of 0.697. The chi square test demonstrated that the overall perfect adherence was not significantly associated with the number of medications taken per day variable (p = 0.721). The Romanian version of the Hill-Bone Compliance to High Blood Pressure Therapy Scale demonstrated suitability for its use in evaluating adherence in the intended population.

Preclinical Studies of Canagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, and Donepezil Combined Therapy in Alzheimer's Disease.

The incidence of neurodegenerative diseases, such as Alzheimer's disease (AD), is continuously growing worldwide, which leads to a heavy economic and societal burden. The lack of a safe and effective causal therapy in cognitive decline is an aggravating factor and requires investigations into the repurposing of commonly used drugs. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new and efficient class of hypoglycemic drugs and, due to their pleiotropic effects, have indications that go beyond diabetes. There is emerging data from murine studies that SGLT2i can cross the blood-brain barrier and may have neuroprotective effects, such as increasing the brain-derived neurotrophic factor (BDNF), reducing the amyloid burden, inhibiting acetylcholinesterase (AChE) and restoring the circadian rhythm in the mammalian target of rapamycin (mTOR) activation. The current study investigates the effect of an SGLT2i and donepezil, under a separate or combined 21-day treatment on AD-relevant behaviors and brain pathology in mice. The SGLT2i canagliflozin was found to significantly improve the novelty preference index and the percentage of time spent in the open arms of the maze in the novel object recognition and elevated plus maze test, respectively. In addition, canagliflozin therapy decreased AChE activity, mTOR and glial fibrillary acidic protein expression. The results also recorded the acetylcholine M1 receptor in canagliflozin-treated mice compared to the scopolamine group. In the hippocampus, the SGLT2i canagliflozin reduced the microgliosis and astrogliosis in males, but not in female mice. These findings emphasize the value of SGLT2i in clinical practice. By inhibiting AChE activity, canagliflozin represents a compound that resembles AD-registered therapies in this respect, supporting the need for further evaluation in dementia clinical trials.

Therapeutic Implications of Renin-Angiotensin System Modulators in Alzheimer's Dementia.

The Renin-Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer's dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and renin inhibitors in AD. ACEIs, commonly used for hypertension, show promise in AD by reducing angiotensin (Ang) II levels. This reduction is significant as Ang II contributes to neuroinflammation, oxidative stress, and ß-amyloid (Aß) accumulation, all implicated in AD pathogenesis. ARBs, known for vasodilation, exhibit neuroprotection by blocking Ang II receptors, improving cerebral blood flow and cognitive decline in AD models. Renin inhibitors offer a novel approach by targeting the initial RAS step, displaying anti-inflammatory and antioxidant effects that mitigate AD degeneration. Preclinical studies demonstrate RAS regulation's favorable impact on neuroinflammation, neuronal damage, cognitive function, and Aß metabolism. Clinical trials on RAS modulators in AD are limited, but with promising results, ARBs being more effective that ACEIs in reducing cognitive decline. The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies.

The Impact of Some Modulators of the Renin-Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model.

As some of the renin-angiotensin-aldosterone system (RAAS)-dependent mechanisms underlying the cognitive performance modulation could include oxidative balance alterations, in this study we aimed to describe some of the potential interactions between RAAS modulators (Losartan and Ramipril) and oxidative stress in a typical model of memory impairment. In this study, 48 white male Swiss mice were divided into six groups and received RAAS modulators (oral administration Ramipril 4 mg/kg, Losartan 20 mg/kg) and a muscarinic receptors inhibitor (intraperitoneal injection scopolamine, 0.5 mg/kg) for 8 consecutive days. Then, 24 h after the last administration, the animals were euthanized and whole blood and brain tissues were collected. Biological samples were then processed, and biochemical analysis was carried out to assess superoxide dismutase and glutathione activities and malondialdehyde concentrations. In the present experimental conditions, we showed that RAAS modulation via the angiotensin-converting enzyme inhibition (Ramipril) and via the angiotensin II receptor blockage (Losartan) chronic treatments could lead to oxidative stress modulation in a non-selective muscarinic receptors blocker (scopolamine) animal model. Our results showed that Losartan could exhibit a significant systemic antioxidant potential partly preventing the negative oxidative effects of scopolamine and a brain antioxidant potential, mainly by inhibiting the oxidative-stress-mediated cellular damage and apoptosis. Ramipril could also minimize the oxidative-mediated damage to the lipid components of brain tissue resulting from scopolamine administration. Both blood serum and brain changes in oxidative stress status were observed following 8-day treatments with Ramipril, Losartan, scopolamine, and combinations. While the serum oxidative stress modulation observed in this study could suggest the potential effect of RAAS modulation and scopolamine administration on the circulatory system, blood vessels endothelia, and arterial tension modulation, the observed brain tissues oxidative stress modulation could lead to important information on the complex interaction between renin-angiotensin and cholinergic systems.

Exploring the Therapeutic Potential of Cannabinoid Receptor Antagonists in Inflammation, Diabetes Mellitus, and Obesity.

Recently, research has greatly expanded the knowledge of the endocannabinoid system (ECS) and its involvement in several therapeutic applications. Cannabinoid receptors (CBRs) are present in nearly every mammalian tissue, performing a vital role in different physiological processes (neuronal development, immune modulation, energy homeostasis). The ECS has an essential role in metabolic control and lipid signaling, making it a potential target for managing conditions such as obesity and diabetes. Its malfunction is closely linked to these pathological conditions. Additionally, the immunomodulatory function of the ECS presents a promising avenue for developing new treatments for various types of acute and chronic inflammatory conditions. Preclinical investigations using peripherally restricted CBR antagonists that do not cross the BBB have shown promise for the treatment of obesity and metabolic diseases, highlighting the importance of continuing efforts to discover novel molecules with superior safety profiles. The purpose of this review is to examine the roles of CB1R and CB2Rs, as well as their antagonists, in relation to the above-mentioned disorders.

Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified Cannabis sativa L. in Rodents.

The conundrum of Cannabis sativa's applications for therapeutical purposes is set apart by the hundreds of known and commercially available strains, the social, cultural and historical context, and the legalization of its use for medical purposes in various jurisdictions around the globe. In an era where targeted therapies are continuously being developed and have become the norm, it is imperative to conduct standardized, controlled studies on strains currently cultivated under Good Manufacturing Practices (GMP) certification, a standard that guarantees the quality requirements for modern medical and therapeutic use. Thus, the aim of our study is to evaluate the acute toxicity of a 15.6% THC: <1% CBD, EU-GMP certified, Cannabis sativa L. in rodents, following the OECD acute oral toxicity guidelines, and to provide an overview of its pharmacokinetic profile. Groups of healthy female Sprague-Dawley rats were treated orally with a stepwise incremental dose, each step using three animals. The absence or presence of plant-induced mortality in rats dosed at one step determined the next step. For the EU GMP-certified Cannabis sativa L. investigated, we determined an oral LD50 value of over 5000 mg/kg in rats and a human equivalent oral dose of ≈806.45 mg/kg. Additionally, no significant clinical signs of toxicity or gross pathological findings were observed. According to our data, the toxicology, safety and pharmacokinetic profile of the tested EU-GMP-certified Cannabis sativa L. support further investigations through efficacy and chronic toxicity studies in preparation for potential future clinical applications and especially for the treatment of chronic pain.

Self-Medication in Rural Northeastern Romania: Patients' Attitudes and Habits.

In recent years, many healthcare systems, along with healthcare professionals, have provided services in a patient-centered manner, in which patients are key actors in the care process. Encouraging self-care creates responsible patients, but it must be practiced responsibly. This study aims to analyze the tendency towards self-medication for patients from a rural area in Northeastern Romania. Data were collected using a questionnaire, which consisted of 25 questions, that has been developed by the research team. Student's T test or one-way ANOVA was used, and the reliability of the questionnaire was calculated using Cronbach's alpha coefficient. Fifty-eight patients agreed to participate and were interviewed. The results of the study suggest that respondents practice self-medication, which they resort to when their condition cannot be treated with natural remedies or herbs and when it impairs their ability to do their daily activities. Self-medication could be explained by the lack of self-care services as well as the trust patients have in the specific treatment. Patients prefer asking the pharmacist for drugs instead of visiting a physician, which could be due to higher accessibility and time-efficiency, while also being prone to stock up on certain medications due to limited access to healthcare.

Impact of the Renin-Angiotensin System on the Pathogeny and Pharmacotherapeutics of Neurodegenerative Diseases.

Brain neurodegenerative diseases (BND) are debilitating conditions that are especially characteristic of a certain period of life and considered major threats to human health. Current treatments are limited, meaning that there is a challenge in developing new options that can efficiently tackle the different components and pathophysiological processes of these conditions. The renin-angiotensin-aldosterone system (RAS) is an endocrine axis with important peripheral physiological functions such as blood pressure and cardiovascular homeostasis, as well as water and sodium balance and systemic vascular resistance-functions which are well-documented. However, recent work has highlighted the paracrine and autocrine functions of RAS in different tissues, including the central nervous system (CNS). It is known that RAS hyperactivation has pro-inflammatory and pro-oxidant effects, thus suggesting that its pharmacological modulation could be used in the management of these conditions. The present paper underlines the involvement of RAS and its components in the pathophysiology of BNDs such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), Huntington's disease (HD), motor neuron disease (MND), and prion disease (PRD), as well as the identification of drugs and pharmacologically active substances that act upon RAS, which could alleviate their symptomatology or evolution, and thus, contribute to novel therapeutic approaches.

Exploring the Involvement of the Amyloid Precursor Protein A673T Mutation against Amyloid Pathology and Alzheimer's Disease in Relation to Therapeutic Editing Tools.

Alzheimer's disease (AD) is biologically defined as a complex neurodegenerative condition with a multilayered nature that leads to a progressive decline in cognitive function and irreversible neuronal loss. It is one of the primary diseases among elderly individuals. With an increasing incidence and a high failure rate for pharmaceutical options that are merely symptom-targeting and supportive with many side effects, there is an urgent need for alternative strategies. Despite extensive knowledge on the molecular basis of AD, progress concerning effective disease-modifying therapies has proven to be a challenge. The ability of the CRISPR-Cas9 gene editing system to help identify target molecules or to generate new preclinical disease models could shed light on the pathogenesis of AD and provide promising therapeutic possibilities. Here, we sought to highlight the current understanding of the involvement of the A673T mutation in amyloid pathology, focusing on its roles in protective mechanisms against AD, in relation to the recent status of available therapeutic editing tools.

Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty.

Neurodegenerative diseases are an increasing cause of global morbidity and mortality. They occur in the central nervous system (CNS) and lead to functional and mental impairment due to loss of neurons. Recent evidence highlights the link between neurodegenerative and inflammatory diseases of the CNS. These are typically associated with several neurological disorders. These diseases have fundamental differences regarding their underlying physiology and clinical manifestations, although there are aspects that overlap. The endocannabinoid system (ECS) is comprised of receptors (type-1 (CB1R) and type-2 (CB2R) cannabinoid-receptors, as well as transient receptor potential vanilloid 1 (TRPV1)), endogenous ligands and enzymes that synthesize and degrade endocannabinoids (ECBs). Recent studies revealed the involvement of the ECS in different pathological aspects of these neurodegenerative disorders. The present review will explore the roles of cannabinoid receptors (CBRs) and pharmacological agents that modulate CBRs or ECS activity with reference to Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD) and multiple sclerosis (MS).

Chemical Composition and Antioxidant Activity of Ammi visnaga L. Essential Oil.

The present study evaluated the chemical composition and the in vitro and in vivo antioxidant potential of Ammi visnaga L. essential oil to provide a scientific basis for the use of this plant in the traditional pharmacopoeia. Gas chromatography-mass spectrometry was used to identify the volatile constituents present of the oil. The in vitro antioxidant capacity was evaluated by the DPPH and the reducing power assays. For the in vivo tests, oral administration of Ammi visnaga L. oil (600 and 1200 mg/kg body weight) was performed in Swiss albino mice treated with acetaminophen (400 mg/kg). The toxic effect of acetaminophen and the action of the essential oil were measured by determining the levels of lipid peroxidation and antioxidant enzymes in liver and kidneys homogenates. The major components identified were butanoic acid, 2-methyl-, pentyl ester, (Z)-ß-ocimene, D-limonene, linalool, pulegone and lavandulyl-butyrate. The in vitro DPPH and reducing power assays showed moderate to low free radical scavenging activity and the antioxidant power was positively correlated with the polyphenols' concentration. In vivo, the Ammi visnaga L. essential oil showed a high antioxidant capacity at both concentrations (600 and 1200 mg/kg), effectively increasing the levels of reduced glutathione, superoxide dismutase, and catalase and significantly reducing the lipid peroxidation. The results obtained from this study suggest that Ammi visnaga L. could represent a source of molecules with antioxidant potential in the prevention of free radical-related diseases.

Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

The most important discoveries in pharmacology, such as certain classes of analgesics or chemotherapeutics, started from natural extracts which have been found to have effects in traditional medicine. Cannabis, traditionally used in Asia for the treatment of pain, nausea, spasms, sleep, depression, and low appetite, is still a good candidate for the development of new compounds. If initially all attention was directed to the endocannabinoid system, recent studies suggest that many of the clinically proven effects are based on an intrinsic chain of mechanisms that do not necessarily involve only cannabinoid receptors. Recent research has shown that major phytocannabinoids and their derivatives also interact with non-cannabinoid receptors such as vanilloid receptor 1, transient receptor ankyrin 1 potential, peroxisome proliferator-activated receptor-gamma or glitazone receptor, G55 protein-coupled receptor, and nuclear receptor, producing pharmacological effects in diseases such as Alzheimer's, epilepsy, depression, neuropathic pain, cancer, and diabetes. Nonetheless, further studies are needed to elucidate the precise mechanisms of these compounds. Structure modulation of phytocannabinoids, in order to improve pharmacological effects, should not be limited to the exploration of cannabinoid receptors, and it should target other courses of action discovered through recent research.

Systemic Actions of SGLT2 Inhibition on Chronic mTOR Activation as a Shared Pathogenic Mechanism between Alzheimer's Disease and Diabetes.

Alzheimer's disease (AD) affects tens of millions of people worldwide. Despite the advances in understanding the disease, there is an increased urgency for pharmacological approaches able of impacting its onset and progression. With a multifactorial nature, high incidence and prevalence in later years of life, there is growing evidence highlighting a relationship between metabolic dysfunction related to diabetes and subject's susceptibility to develop AD. The link seems so solid that sometimes AD and type 3 diabetes are used interchangeably. A candidate for a shared pathogenic mechanism linking these conditions is chronically-activated mechanistic target of rapamycin (mTOR). Chronic activation of unrestrained mTOR could be responsible for sustaining metabolic dysfunction that causes the breakdown of the blood-brain barrier, tau hyperphosphorylation and senile plaques formation in AD. It has been suggested that inhibition of sodium glucose cotransporter 2 (SGLT2) mediated by constant glucose loss, may restore mTOR cycle via nutrient-driven, preventing or even decreasing the AD progression. Currently, there is an unmet need for further research insight into molecular mechanisms that drive the onset and AD advancement as well as an increase in efforts to expand the testing of potential therapeutic strategies aimed to counteract disease progression in order to structure effective therapies.

From Evidence to Clinical Guidelines in Antibiotic Treatment in Acute Otitis Media in Children.

Acute otitis media (AOM) in children represents a public health concern, being one of the leading causes of health care visits and antibiotic prescriptions worldwide. The overall aim of this paper is to unravel the major current insights into the antibiotic treatment of AOM in children. Our approach is three-fold: 1. a preclinical evaluation of antibiotics in animal models of AOM stressing on the advantages of different species when testing for different schemes of antibiotics; 2. an overview on the new antimicrobial agents whose efficacy has been demonstrated in refractory cases of AOM in children; and 3. an analysis of the different guidelines stressing on the differences and similarities between the various schemes of antibiotic treatment. The preferred therapeutic agents remain amoxicillin and the amoxicillin-clavulanate combination for AOM caused by Streptococcus pneumoniae, whereas oral cephalosporin is preferred in AOM due to Moraxella catarrhalis and Haemophilus influenzae. As for the second and third line antimicrobial treatments, there is a wide variety of suggested antibiotic classes with variations in duration and posology. The decision to prescribe antimicrobial treatment as a first-line choice is based on the severity of the symptoms in 16 of the guidelines included in this review.

Behavioral and Oxidative Stress Changes in Mice Subjected to Combinations of Multiple Stressors Relevant to Irritable Bowel Syndrome.

Background and Objectives: Irritable bowel syndrome (IBS) is a well-known functional gastrointestinal (GI) disorder exhibiting a wide range of symptoms due to individual variability and multifactorial etiology. Stress exposure is a major risk factor for the development of IBS. Here, we investigate the differential effects of psychological stress exposures on behavior and oxidative status in mice by using increasingly complex combinations of etiologic IBS-relevant stressors (maternal separation and chronic unpredictable mild stress combinations). Materials and Methods: Mice were subjected to three different combinations of psychological stress factors and subsequent behavioral cognitive and affective parameters and oxidative status markers (superoxide dismutase and glutathione peroxidase antioxidant activity and malondialdehyde level) in the brain and bowel tissues of the animals were analyzed. Results: GI transit modifications reflected by decreased fecal output, cognitive and affective behavioral deficits were observed in all stress exposed groups, but were more evident for the more complex combinations of stressors. Behavioral deficits were accompanied by mild oxidative stress occurring in the bowel and to a greater extent in brain tissue. Conclusions: The presented data depict the effect of various associations in mimicking IBS symptoms and comorbidities and suggest that an all-inclusive combination of early and adult-life psychological stressors is more effective in IBS symptoms modulation. Oxidative stress in both brain and bowel, suggestive for brain-gut molecular connectivity, may play an important role in IBS mechanistic.

Renal Contributions in the Pathophysiology and Neuropathological Substrates Shared by Chronic Kidney Disease and Alzheimer's Disease.

Chronic kidney disease and Alzheimer's disease are chronic conditions highly prevalent in elderly communities and societies, and a diagnosis of them is devastating and life changing. Demanding therapies and changes, such as non-compliance, cognitive impairment, and non-cognitive anomalies, may lead to supplementary symptoms and subsequent worsening of well-being and quality of life, impacting the socio-economic status of both patient and family. In recent decades, additional hypotheses have attempted to clarify the connection between these two diseases, multifactorial in their nature, but even so, the mechanisms behind this link are still elusive. In this paper, we sought to highlight the current understanding of the mechanisms for cognitive decline in patients with these concurrent pathologies and provide insight into the relationship between markers related to these disease entities and whether the potential biomarkers for renal function may be used for the diagnosis of Alzheimer's disease. Exploring detailed knowledge of etiologies, heterogeneity of risk factors, and neuropathological processes associated with these conditions opens opportunities for the development of new therapies and biomarkers to delay or slow their progression and validation of whether the setting of chronic kidney disease could be a potential determinant for cognitive damage in Alzheimer's disease.

Oxytocin Differentiated Effects According to the Administration Route in a Prenatal Valproic Acid-Induced Rat Model of Autism.

Background and objectives: The hormone oxytocin (OXT) has already been reported in both human and animal studies for its promising therapeutic potential in autism spectrum disorder (ASD), but the comparative effectiveness of various administration routes, whether central or peripheral has been insufficiently studied. In the present study, we examined the effects of intranasal (IN) vs. intraperitoneal (IP) oxytocin in a valproic-acid (VPA) autistic rat model, focusing on cognitive and mood behavioral disturbances, gastrointestinal transit and central oxidative stress status. Materials and Methods: VPA prenatally-exposed rats (500 mg/kg; age 90 days) in small groups of 5 (n = 20 total) were given OXT by IP injection (10 mg/kg) for 8 days consecutively or by an adapted IN pipetting protocol (12 IU/kg, 20 µL/day) for 4 consecutive days. Behavioral tests were performed during the last three days of OXT treatment, and OXT was administrated 20 minutes before each behavioral testing for each rat. Biochemical determination of oxidative stress markers in the temporal area included superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). A brief quantitative assessment of fecal discharge over a period of 24 hours was performed at the end of the OXT treatment to determine differences in intestinal transit. Results: OXT improved behavioral and oxidative stress status in both routes of administration, but IN treatment had significantly better outcome in improving short-term memory, alleviating depressive manifestations and mitigating lipid peroxidation in the temporal lobes. Significant correlations were also found between behavioral parameters and oxidative stress status in rats after OXT administration. The quantitative evaluation of the gastrointestinal (GI) transit indicated lower fecal pellet counts in the VPA group and homogenous average values for the control and both OXT treated groups. Conclusions: The data from the present study suggest OXT IN administration to be more efficient than IP injections in alleviating autistic cognitive and mood dysfunctions in a VPA-induced rat model. OXT effects on the cognitive and mood behavior of autistic rats may be associated with its effects on oxidative stress. Additionally, present results provide preliminary evidence that OXT may have a balancing effect on gastrointestinal motility.

Link Between Diabetes and Alzheimer's Disease due to the Shared Amyloid Aggregation and Deposition Involving both Neurodegenerative Changes and Neurovascular Damages.

Diabetes and Alzheimer's disease are two highly prevalent diseases among the aging population and have become major public health concerns in the 21st century, with a significant risk to each other. Both of these diseases are increasingly recognized to be multifactorial conditions. The terms "diabetes type 3" or "brain diabetes" have been proposed in recent years to provide a complete view of the potential common pathogenic mechanisms between these diseases. While insulin resistance or deficiency remains the salient hallmarks of diabetes, cognitive decline and non-cognitive abnormalities such as impairments in visuospatial function, attention, cognitive flexibility, and psychomotor speed are also present. Furthermore, amyloid aggregation and deposition may also be drivers for diabetes pathology. Here, we offer a brief appraisal of social impact and economic burden of these chronic diseases and provide insight into amyloidogenesis through considering recent advances of amyloid-ß aggregates on diabetes pathology and islet amyloid polypeptide on Alzheimer's disease. Exploring the detailed knowledge of molecular interaction between these two amyloidogenic proteins opens new opportunities for therapies and biomarker development.