Grape seed extract protects rat offspring hippocampus from the silicon dioxide nanoparticles' neurotoxicity.

Silicon dioxide nanoparticles (SiO2-NPs) can be found in many products, such as composites, paints, ceramics, consumer products, and food additives. We recently demonstrated that via breastfeeding, SiO2-NPs transfer to the offspring's brain, interfering negatively with hippocampus development. In this work, we evaluated the protective effect of grape seed extract (GSE) against the adverse effects of SiO2-NPs. After delivery, animals were administered 25 mg/kg SiO2-NPs with/without GSE (300 mg/kg) for 20 days (from 2nd to 21st days post-delivery) by gavage. SiO2-NPs increased malondialdehyde concentration and decreased antioxidant activity in the offspring's hippocampi. The mean number of dark neurons (DNs) was significantly higher in the hippocampi of the SiO2-NPs group, whereas the mean number of DCX + cells was significantly lower than in the control group. The offspring in the SiO2-NPs groups had a weak cognitive performance in adulthood. Interestingly, these adverse effects of SiO2-NPs were alleviated in the GSE-treated groups. Therefore, GSE can attenuate the damaging effects of maternal exposure to SiO2-NPs during lactation.

Vitamin D alleviates hypothyroidism associated liver dysfunction: Histological and biochemical evidence.

There is a complex correlation between thyroid hormones (THs) and liver function. Hypothyroidism as a failure of the thyroid gland to produce adequate thyroid hormones to fulfill the metabolic requirements of the body, may perturb liver structure and function. Emerging evidence suggests the protective effects of vitamin D against liver damage. Herein, this study aimed to investigate the role of vitamin D in hypothyroidism-associated liver injury. Forty male Wistar rats were classified into 4 groups: control, hypothyroid (Hypo) group received 0.05% PTU, Hypo- Vitamin D groups were given 100 and 500 IU/kg vitamin D orally via gavage for 6 weeks. Serum level of liver function including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured. Malondialdehyde (MDA) level, superoxide dismutase (SOD) enzyme activity, and total thiol content were measured as oxidative stress indicators in the liver tissue. Furthermore, to estimate liver tissue fibrosis, Masson's trichrome staining was done. Our findings showed that hypothyroidism-induced liver fibrosis was associated with increased levels of ALT, AST and ALP. Though, vitamin D administration could significantly reduce the ALT, AST and ALP in the serum and suppress the accumulation of collagen fibers. Moreover, the activity of SOD and total thiol content was notably reduced, while the MDA content was significantly increased in the PTU- induced hypothyroid rats compared to the control group. Nonetheless, treatment with vitamin D improved mentioned oxidative stress markers in the Hypo-vitamin D groups. In conclusion, vitamin D due to its potential antioxidant and anti-fibrotic properties could be effective in the decrease of hypothyroidism-associated liver injury.

Therapeutic Potentials of MicroRNA-126 in Cerebral Ischemia.

Stroke is a leading cause of death and disability worldwide. It is among the most common neurological disorders with an 8-10% lifetime risk. Ischemic stroke accounts for about 85% of all strokes and damages the brain tissue via various damaging mechanisms. Following cerebral ischemia, the disrupted blood-brain barrier (BBB) leads to cerebral edema formation caused by activation of oxidative stress, inflammation, and apoptosis, targeting primarily endothelial cells. Activation of the protective mechanisms might favor fewer damages to the neural tissue. MicroRNA (miR)-126 is an endothelial cell-specific miR involved in angiogenesis. MiR-126 orchestrates endothelial progenitor cell functions under hypoxic conditions and could inhibit ischemia-induced oxidative stress and inflammation. It alleviates the BBB disruption by preventing an augment in matrix metalloproteinase level and halting the decrease in the junctional proteins, including zonula occludens-1 (ZO-1), claudin-5, and occludin levels. Moreover, miR-126 enhances post-stroke angiogenesis and neurogenesis. This work provides a therapeutic perspective for miR-126 as a new approach to treating cerebral ischemia.

Roles of the miR-155 in Neuroinflammation and Neurological Disorders: A Potent Biological and Therapeutic Target.

Neuroinflammation plays a crucial role in the development and progression of neurological disorders. MicroRNA-155 (miR-155), a miR is known to play in inflammatory responses, is associated with susceptibility to inflammatory neurological disorders and neurodegeneration, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis as well as epilepsy, stroke, and brain malignancies. MiR-155 damages the central nervous system (CNS) by enhancing the expression of pro-inflammatory cytokines, like IL-1ß, IL-6, TNF-α, and IRF3. It also disturbs the blood-brain barrier by decreasing junctional complex molecules such as claudin-1, annexin-2, syntenin-1, and dedicator of cytokinesis 1 (DOCK-1), a hallmark of many neurological disorders. This review discusses the molecular pathways which involve miR-155 as a critical component in the progression of neurological disorders, representing miR-155 as a viable therapeutic target.

Anti-apoptotic and neurogenic properties in the hippocampus as possible mechanisms for learning and memory improving impacts of vitamin D in hypothyroid rats during the growth period.

The current study was designed to investigate the protective effects of Vitamin D (VD) on hippocampal neurogenesis, apoptosis, and subsequent hippocampal-dependent learning and memory performance in hypothyroid juvenile rats. Twenty eight male Wistar rats were randomly divided into four groups as; control, Hypothyroid (Hypo), Hypo-VD100 and Hypo-VD500. Hypothyroidism was induced by giving 0.05 % propylthiouracil (PTU), and VD (100 or 500 IU/kg) treatment was performed daily by gavage. At the end of treatment, Morris water maze (MWM) was carried out and evaluated hippocampal neurogenesis, apoptosis, and dark neurons (DNs). Our results revealed that the escape latency and the traveled distance to find the platform in the Hypo group were significantly longer but the time spent and distance traveled in the target area in probe trial was lower than the control group. Hypothyroidism was accompanied by a marked decrease in hippocampal neurogenesis, and a significant increase in the number of apoptotic neurons and DNs compared to the control group. VD decreased escape latency and the traveled distance to find the platform but increased the time spent and distance traveled in the target area in probe trial than the Hypo group. VD also increased neurogenesis, reduced apoptosis and DNs production compared to the Hypo group. In conclusion, these results support a role for VD in the restoring hippocampal neurogenesis impairment, reducing neuronal apoptosis, and DNs in hypothyroid rats as well as raise the possibility that VD may contribute as a therapeutic approach to improve the learning and memory deficits associated with hypothyroidism.

Targeting miR-21 in spinal cord injuries: a game-changer?

Spinal cord injury (SCI) is a devastating neurological state causing physical disability, psychological stress and financial burden. SCI global rate is estimated between 250,000 and 500,000 individuals every year, of which 60% of victims are young, healthy males between 15 and 35 years. A variety of pathological conditions such as neuroinflammation, mitochondrial dysfunction, apoptosis, glial scar formation, blood-spinal cord barrier disruption, and angiogenesis disruption occur after SCI leading to a limitation in recovery. MicroRNAs (miRs) are endogenous and non-coding RNAs consisting of 22 nucleotides that regulate 60% of all human genes and involve several normal physiological processes and pathological conditions. miR-21 is among the most highly expressed miRs and its expression has been shown to increase one day after SCI and this elevation is sustained up to 28 days after injury. Overexpression of miR-21 exerts many protective effects against SCI by inhibiting neuroinflammation, improving blood-spinal cord barrier function, regulating angiogenesis, and controlling glial scar formation. It also exhibits anti-apoptotic effects in SCI by down-regulating the expression of PTEN, Spry2, and PDCD4. This review provides a novel therapeutic perspective for miR-21 in SCI.

Cardiovascular protective effect of nano selenium in hypothyroid rats: protection against oxidative stress and cardiac fibrosis.

BACKGROUND: Nano selenium (Nano Sel) has many therapeutic properties including antioxidant, anticancer, and anti-inflammatory actions. OBJECTIVE: Impacts of Nano Sel administration against cardiac fibrosis and heart and aorta tissue oxidative damage observed in hypothyroid rats were explored. METHODS: The animals were randomly grouped and treated as: 1) Control; 2) Propylthiouracil (PTU) in which PTU was added to the drinking water (0.05%) to induce hypothyroidism; 3-5) PTU-Nano Sel 50, PTU-Nano Sel 100, and PTU-Nano Sel 150 groups, which received daily PTU plus 50,100 or 150 µg/kg of Nano Sel for 6 weeks intraperitoneally. The heart and aorta tissues were removed under deep anesthesia and then biochemical parameters including malondialdehyde (MDA), total thiol groups, catalase (CAT), and superoxide dismutase (SOD), as well as cardiac fibrosis were assessed. RESULTS: Hypothyroidism induced by PTU was remarkably associated with myocardial hypertrophy and perivascular fibrosis in Masson's trichrome staining. Moreover, hypothyroidism increased MDA level, while it subtracted total thiol group content and activity of SOD and CAT. Treatment with Nano Sel recovered hypothyroidism-induced cardiac fibrosis in the histological assessment. Nano Sel also promoted CAT and SOD activity and thiol content, whereas alleviated MDA levels in the heart and aorta tissues. CONCLUSION: Results propose that administration of Nano Sel exerts a protective role in the cardio vascular system via preventing cardiac fibrosis and inhibiting oxidative stress.

MicroRNA-22: a Novel and Potent Biological Therapeutics in Neurological Disorders.

MicroRNAs (miRs) are regulatory RNAs with 18-25 nucleotides lengths involved in various biological processes. Some miRs, including miR-22, play an essential role in regulating neurological disorders. MiR-22 is a brain-enriched regulatory element involved in angiogenesis, energy supply, adjustment of ionic channels, and suppression of malignant cell proliferation, migration, and invasion. This article discusses the protective and therapeutic effects of miR-22 on neurological diseases and injuries, including cerebral ischemia, neurodegenerative diseases, epilepsy, and brain malignancies. We also correlated miR-22 with amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), panic disorders, schizophrenia, neural tube defect (anencephaly), and traumatic brain injury. This work provides a therapeutic perspective for miR-22 as a new approach in treating neurological disorders.

The effects of vitamin D on learning and memory of hypothyroid juvenile rats and brain tissue acetylcholinesterase activity and oxidative stress indicators.

Apart from a role as a key regulator of calcium/phosphate homeostasis, vitamin D (Vit D) is suggested to be a potential player in nervous system growth and function. This study aimed to assess the impacts of Vit D administration on memory impairment, oxidative damage, and acetylcholinesterase (AchE) overactivity in hypothyroid juvenile rats. The animals were randomly grouped as (1) Control; (2) Hypothyroid; (3) Hypothyroid-Vit D100, and (4) Hypothyroid-Vit D 500. Propylthiouracil (PTU) was added to their drinking water (0.05%) for 6 weeks, and Vit D (100 or 500 IU/kg) treatment was performed daily by gavage. Morris water maze (MWM) and passive avoidance (PA) tests were performed. The brains were removed under deep anesthesia, then the hippocampal and cortical tissues were separated to assess biochemical parameters. Hypothyroidism was significantly associated with learning and memory impairment in MWM and PA tests. Hypothyroidism was also accompanied by an elevation in AChE activity and malondialdehyde (MDA) content and a reduced level of thiol content and superoxide dismutase (SOD) activity in the brain. Treatment with Vit D recovered hypothyroidism-induced cognitive impairment and improved memory performance in MWM and PA tasks. On the other hand, Vit D alleviated AChE activity and MDA level, whereas increased SOD activity and thiol content in the hippocampal and cortical tissues. In conclusion, these outcomes suggest an association between the oral administrations of Vit D and learning and memory improvement of hypothyroid rats, which was accompanied by decreasing AChE activity and brain tissue oxidative damage.

Maternal exposure to silicon dioxide nanoparticles reduces hippocampal neurogenesis and synaptogenesis and induces neurodegeneration in rat offspring hippocampus.

Silicon dioxide nanoparticles (SiO2-NPs) are among the most widely used nanoparticles because of their chemical-physical properties. Since most brain maturation occurs in the neonatal period in humans and many mammals, it is important to understand how NPs may affect this process. This study tested the hypothesis that SiO2-NPs from treated dams could affect the hippocampus of neonatal rats during lactation. Twenty-four pregnant rats, after delivery, were divided into three groups of control, SiO2-NPs (25 mg/kg) and SiO2-NPs (100 mg/kg). The rats were treated from 2nd to 21st days post-delivery by gavage and the effects of these NPs were evaluated in the offspring's hippocampi to reveal the effects of maternal exposure to SiO2-NPs during lactation on the offspring's hippocampi. The offspring in the SiO2-NPs groups had higher malondialdehyde concentration and lower antioxidant activity in the hippocampi than the non-treated control group. The mean number of doublecortin positive (DCX+) cells and synaptophysin expression in the hippocampi of the SiO2-NPs groups were significantly lower than the control group, whereas the mean number of dark neurons was significantly higher. Also, animals in the SiO2-NPs groups had a weak cognitive performance in adulthood. In conclusion, maternal exposure to SiO2-NPs via breastfeeding could affect offspring's hippocampal neurogenesis and synaptogenesis, leading to impaired cognitive performance.

Grape seed extract effects on hippocampal neurogenesis, synaptogenesis and dark neurons production in old mice. Can this extract improve learning and memory in aged animals?

BACKGROUND: During the elderly, hippocampal neurogenesis and synaptogenesis reduce and dark neurons (DNs) increase, leading to cognitive impairment. It is believed that natural products can protect the neural cells and system by protecting from damages or promoting regeneration. Therefore, the effects of grape seed extract (GSE) on the hippocampus of aged mice were investigated in this study. METHODS: twelve old mice were divided into two groups of control and GSE. Animals in the GSE group received 300 mg/kg of GSE for eight weeks via gavage. At the end of treatment, cognition performance was evaluated by Morris water maze (MWM) and passive avoidance tests. Hippocampal neurogenesis, synaptogenesis and DNs production were evaluated with immunohistochemistry and histological evaluations on 5-micron coronal tissue sections. RESULTS: The hippocampal mean number of double cortin positive cells (DCX+) per unit area, as well as synaptophysin expression in the GSE group, were significantly higher than the control group (p < 0.01). The frequency of DNs in the GSE group was lower than the control group (p < 0.05). Behavioral tests showed that GSE improves memory and learning performance. CONCLUSION: Consuming GSE in the elderly can potentially alleviate the age-related reduction of hippocampal neurogenesis and synaptogenesis. It is also able to decrease hippocampal DNs production and increase memory and learning.

Cell and molecular toxicity of lanthanum nanoparticles: are there possible risks to humans?

Lanthanum nanoparticles are widely used in industry, agriculture, and biomedicine. Over 900 kg of lanthanum is annually released into the environment only in Europe, 50 times higher than the metals, mercury, and cadmium's environmental spread. Human health risk associated with long-term exposure to the abundant lanthanum nanoparticles is a concerning environmental issue. Due to lanthanum's ability to disrupt the main biological barriers and interrupt various cells' hemostasis, they seem to cause severe disruptions to various tissues. This review opens a new perspective regarding the cellular and molecular interaction of nanosized and ionic lanthanum with the possible toxicity on the nervous system and other tissues that would show lanthanum nanoparticles' potential danger to follow in toxicological science.