Anandamide Attenuates Neurobehavioral Deficits and EEG Irregularities in the Chronic Sleep Deprivation Rats: The Role of Oxidative Stress and Neuroinflammation.

Sleep deprivation increases stress, anxiety, and depression by altering the endocannabinoid system's function. In the present study, we aimed to investigate the anti-anxiety and anti-depressant effects of the endocannabinoid anandamide (AEA) in the chronic sleep deprivation (SD) model in rats. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation + 20 mg/kg AEA (SD + A). The rats were kept in a sleep deprivation device for 18 h (7 to 1 a.m.) daily for 21 days. Open-field (OFT), elevated plus maze, and forced swimming tests (FST) were used to assess anxiety and depression-like behavior. As well as the cortical EEG, CB1R mRNA expression, TNF-α, IL-6, IL-4 levels, and antioxidant activity in the brain were examined following SD induction. AEA administration significantly increased the time spent (p < 0.01), the distance traveled in the central zone (p < 0.001), and the number of climbing (p < 0.05) in the OFT; it also increased the duration and number of entries into the open arms (p < 0.01 and p < 0.05 respectively), and did not reduce immobility time in the FST (p > 0.05), AEA increased CB1R mRNA expression in the anterior and medial parts of the brain (p < 0.01), and IL-4 levels (p < 0.05). AEA also reduced IL-6 and TNF-α (p < 0.05) and modulated cortical EEG. AEA induced anxiolytic-like effects but not anti-depressant effects in the SD model in rats by modulating CB1R mRNA expression, cortical EEG, and inflammatory response.

Epidemiological characteristics of human cystic echinococcosis in Khuzestan province (Iran), 2011-2021: a retrospective analytical study.

Hydatid cyst (HC) disease is endemic in many Mediterranean countries. The most polluted areas of Iran include the Alborz and Zagros Mountain ranges, where animal husbandry is common. This study investigated the epidemiological dimensions of HC in patients admitted to hospitals in Khuzestan province from 2011 to 2021. Of all 183 patients identified, 113 (61.7%) were female with the mean age of 37.7 ± 17, men with the mean age of 36.7 ± 19. Also, we found that housewives made up 49.2% of our HC patients. 65% of the patients in this study lived in urban areas, and 42% had a history of contact with dogs. The liver was reported to be the most HC-affected organ. The most clinical symptoms were abdominal pain and hepatomegaly. 59% of the patients had only one cyst. This study found that surgery and radiology were the most common treatment and diagnostic methods. There were significant relationships between: gender and occupation (p < 0.001); location with dog contact, duration of dog contact (p < 0.001); ways of washing raw vegetables (p < 0.01), and type of treatment (p < 0.05); occupation and dog contact (p < 0.001); with the involvement of the liver being greater in patients who used only water to wash vegetables (p < 0.01). The key to successful disease management is early diagnosis. How to intervene and treat HC necessitates the identification of the stages of the cyst, which is dependent on imaging techniques. The prevalence of human hydatidosis has been overlooked as the most important disease that health policymakers should consider. Furthermore, training programs are required to better understand the disease's symptoms and identify sources of infection.

Anandamide improves food intake and orexinergic neuronal activity in the chronic sleep deprivation induction model in rats by modulating the expression of the CB1 receptor in the lateral hypothalamus.

Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation +20 mg/kg AEA (SD + A). For SD induction, the rats were kept in a sleep deprivation device for 18 h (7 a.m. to 1 a.m.) daily for 21 days. Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. Our results showed that AEA administration significantly improved food intake (p < 0.01), Electrical activity of orexin neurons (p < 0.05), CB1R expression in the hypothalamus (p < 0.05), and IL-4 levels (p < 0.05). AEA also reduced mRNA expression of OX1R and OX2R (p < 0.01 and p < 0.05 respectively), also IL-6 and TNF-α (p < 0.01) and MDA level (p < 0.05) in hypothalamic tissue. As a consequence, AEA modulates orexinergic system function and improves food intake by regulating the expression of the CB1 receptor in the LH in sleep deprived rats.

Mitochondrial Dysfunction and Parkinson's Disease: Pathogenesis and Therapeutic Strategies.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder whose pathogenesis is not completely understood. Mitochondrial dysfunction and increased oxidative stress have been considered as major causes and central events responsible for the progressive degeneration of dopaminergic (DA) neurons in PD. Therefore, investigating mitochondrial disorders plays a role in understanding the pathogenesis of PD and can be an important therapeutic target for this disease. This study discusses the effect of environmental, genetic and biological factors on mitochondrial dysfunction and also focuses on the mitochondrial molecular mechanisms underlying neurodegeneration, and its possible therapeutic targets in PD, including reactive oxygen species generation, calcium overload, inflammasome activation, apoptosis, mitophagy, mitochondrial biogenesis, and mitochondrial dynamics. Other potential therapeutic strategies such as mitochondrial transfer/transplantation, targeting microRNAs, using stem cells, photobiomodulation, diet, and exercise were also discussed in this review, which may provide valuable insights into clinical aspects. A better understanding of the roles of mitochondria in the pathophysiology of PD may provide a rationale for designing novel therapeutic interventions in our fight against PD.

Evaluation of skin absorption of the Citrullus colocynthis in treatment of type II diabetic patients.

BACKGROUND AND PURPOSE: Nowadays, among the herbal medicines utilized to treat diabetes, Citrullus colocynthis (CCT) is highly noticeable as it reduces blood glucose (BG) and stimulating insulin secretion. However, long-term oral consumption of this herbal medicine has often associated with digestive complications. In this study, skin absorption of CCT as a new therapeutic approach in the treatment of type II diabetic patients has been surveyed. MATERIALS AND METHODS: 40 patients with type II diabetic (aged 45-65) were selected. Participants were asked for placing their metatarsus daily in a decoction containing 2% CCT solution for 40-60 min each day and continuing that for 10 days. Blood and urine samples of patients collected at the beginning and the end of the study. The samples were examined for the BG levels, serum insulin content, lipid profiles, hepatic enzymes, urea, creatinine, and microalbuminuria, The quantitative insulin sensitivity check index (QUICKI), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), homeostasis model assessment of ß-cell function (HOMA-ß) and disposition index (DI) indicators were also calculated. RESULTS: Local treatment of CCT could significantly decrease BG levels, stimulate insulin secretion and improve the function of pancreatic beta cells. It also decreased serum urea levels comparing to pre-treatment levels (p < 0.05) but there was no significant change in creatinine levels, lipid profiles, hepatic enzymes, micro-albuminuria, and other insulin sensitivity indexes. CONCLUSION: This study demonstrated that the CCT plant can also have systemic therapeutic effects on type II diabetic patients through dermal absorption.

2-Deoxyglucose protects hippocampal neurons against kainate-induced temporal lobe epilepsy by modulating monocyte-derived macrophages (mo-MΦ) and progranulin production in the hippocampus.

Inflammation is an important factor in the pathology of epilepsy with the hallmarks of resident microglia activation and infiltration of circulating monocytes in the damaged area. In the case of recovery and tissue repair, some monocytes change to macrophages (mo-MΦ) to enhance tissue repair. 2-deoxyglucose (2DG) is an analog of glucose capable of protecting the brain, and progranulin is a neurotrophic factor produced mainly by microglia and has an inflammation modulator effect. This study attempted to evaluate if one of the neuroprotective mechanisms of 2-DG is comprised of increasing monocyte-derived macrophages (mo-MΦ) and progranulin production. Status epilepticus (SE) was induced by i.c.v. injection of kainic acid (KA).2DG (125/mg/kg/day) was administered intraperitoneally. Four days later, animals were sacrificed. Their brain sections were then stained with Cresyl violet and Fluoro-Jade B to count the number of necrotic and degenerating neurons in CA3 and Hilus of dentate gyrus of the hippocampus. Lastly, immunohistochemistry was used to detect CD11b + monocyte, macrophage cells, and Progranulin level was evaluated by Western blotting. The histological analysis showed that 2DG can reduce the number of necrotic and degenerating neurons in CA3 and Hilar areas. Following KA administration, a great number of cD11b+ cells with monocyte morphology were observed in the hippocampus. 2DG not only reduced cD11b+ monocyte cells but was able to convert them to cells with the morphology of macrophages (mo-MΦ). 2DG also caused a significant increase in progranulin level in the hippocampus. Because macrophages and microglia are the most important sources of progranulin, it appears that 2DG caused the derivation of monocytes to macrophages and these cells produced progranulin with a subsequent anti-inflammation effect. In summary, it was concluded that 2DG is neuroprotective and probably one of its neuroprotective mechanisms is by modulating monocyte-derived macrophages by progranulin production.

Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.

A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer's disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. Graphical Abstract ᅟ.

Correction to: Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.

The original version of this article unfortunately contained mistake in the affiliation. Affiliation 1 should be read as "Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran". The original article has been corrected.