The Role of Vitamins in Spinal Cord Injury: Mechanisms and Benefits.

Spinal cord injury (SCI) is a common neurological disease worldwide, often resulting in a substantial decrease in quality of life, disability, and in severe cases, even death. Unfortunately, there is currently no effective treatment for this disease. Nevertheless, current basic and clinical evidence suggests that vitamins, with their antioxidant properties and biological functions, may play a valuable role in improving the quality of life for individuals with SCI. They can promote overall health and facilitate the healing process. In this review, we discuss the mechanisms and therapeutic potential of vitamins in the treatment of SCI.

Nanocurcumin prevents memory impairment, hippocampal apoptosis, Akt and CaMKII-α signaling disruption in the central STZ model of Alzheimer's disease in rat.

The central route of streptozotocin (STZ) administration has been introduced as a rat model of sporadic Alzheimer's disease (AD). Curcumin was suggested to possess possible neuroprotective effects, which may be profitable in AD. However, the low bioavailability of curcumin hinders its beneficial effects in clinical studies. Earlier studies suggested that a bovine serum albumin-based nanocurcumin, produces superior neuroprotective effects compared to natural curcumin. In the present study, the protective effect of nanocurcumin in rat model of central STZ induced memory impairment was assessed. In addition, due to the importance of the hippocampus in memory, the amounts of hippocampal active caspase-3, Akt, and CaMKII-α were evaluated. Adult male Wistar rats weighing 250-300 g were used. STZ (icv) was injected during days 1 and 3 (3 mg/kg in divided), and nanocurcumin or curcumin 50 mg/kg/oral gavage was administered daily during days 4-14. Morris water maze training was performed on days 15-17, and the retention memory test was achieved on the 18th day. Following memory assessment, the rats were sacrificed and the hippocampi were used to assess caspase-3 cleavage, Akt, and CaMKII-α signaling. The findings revealed that nanocurcumin ingestion (but not natural curcumin) in the dose of 50 mg/kg was capable to prevent the impairment of water maze learning and memory induced by central STZ. Molecular assessments indicated that STZ treatment increased the caspase-3 cleavage in the hippocampus while deactivating Akt and CaMKII-α. Nanocurcumin reduced caspase-3 cleavage to a non-significant level compared to control group and restored Akt and CaMKII-α within the hippocampus while natural curcumin exerted no significant effect. These findings might suggest that nanocurcumin can restore memory deficit, hippocampal apoptosis as well as Akt and CaMKII-α signaling disruption associated with brain insulin resistance.

Mitochondrial Transportation, Transplantation, and Subsequent Immune Response in Alzheimer's Disease: An Update.

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by memory impairment and a progressive decline in cognitive function. Mitochondrial dysfunction has been identified as an important contributor to the development of AD, leading to oxidative stress and energy deficits within the brain. While current treatments for AD aim to alleviate symptoms, there is an urgent need to target the underlying mechanisms. The emerging field of mitotherapy, which involves the transplantation of healthy mitochondria into damaged cells, has gained substantial attention and has shown promising results. However, research in the context of AD remains limited, necessitating further investigations. In this review, we summarize the mitochondrial pathways that contribute to the progression of AD. Additionally, we discuss mitochondrial transfer among brain cells and mitotherapy, with a focus on different administration routes, various sources of mitochondria, and potential modifications to enhance transplantation efficacy. Finally, we review the limited available evidence regarding the immune system's response to mitochondrial transplantation in damaged brain regions.

Behavioral and Molecular Effects of Thapsigargin-Induced Brain ER- Stress: Encompassing Inflammation, MAPK, and Insulin Signaling Pathway.

Accumulation of misfolded proteins, known as endoplasmic reticulum (ER) stress, is known to participate in Alzheimer's disease (AD). AD is also correlated with impaired central insulin signaling. However, few studies have probed the relationship between memory, central ER stress, inflammation, hippocampal mitogen-activated protein kinase (MAPK) activity and insulin resistance. The present study aimed to investigate the causative role and underlying mechanisms of brain ER stress in memory impairment and develop a reliable animal model for ER-mediated memory loss. Thapsigargin (TG), a known ER stress activator, was centrally administered. The cognitive function of animals was evaluated by the Morris Water Maze (MWM). To verify the induction of central ER stress, we investigated the mRNA expression of UPR markers in the hippocampus. In addition, the activation of ER stress markers, including Bip, CHOP, and some related apoptosis and pro-inflammatory proteins, such as caspase-3, Bax, Bcl-2, TNF-α, MAPK, and insulin signaling markers, were assessed by Western-blots. The results demonstrated that TG impairs spatial cognition and hippocampal insulin signaling. Meanwhile, molecular results showed a concurrent increment of hippocampal UPR markers, apoptosis, P38 activity, and TNF-α. This study introduced TG-induced ER stress as a pharmacological model for memory impairment in rats and revealed some underlying mechanisms.

Imipramine alleviates memory impairment and hippocampal apoptosis in STZ-induced sporadic Alzheimer's rat model: Possible contribution of MAPKs and insulin signaling.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease, associated with several pathophysiological complaints. Impaired insulin signaling in the brain, is one of the important characteristic features of AD which is accompanied by cognitive deficits. According to the multifactorial and complicated pathology of AD, no modifying therapy has been approved yet. Imipramine is a kind of tricyclic antidepressant with reported anti-inflammatory and anti-oxidant effects in the brain. There are controversial studies about the effect of this drug on spatial memory. This study investigates the effect of imipramine on streptozotocin (STZ) induced memory impairment in rats. Pursuing this objective, rats were treated with imipramine 10 or 20 mg/kg i.p. once a day for 14 days. 24 h after the last injection, memory function was evaluated by the Morris water maze (MWM) test in 4 consecutive days. Then, hippocampi were removed and the activity of caspase-3, mitogen activated protein kinases (MAPKs) family and inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1ser307) were analyzed using Western blotting. Results showed that imipramine prevents memory impairment in STZ induced rats and this improvement was accompanied with an increase in ERK activity, reduction of caspase-3 and JNK activity, as well as partial restoration of P38 and IRS-1 activity. In conclusion, our study demonstrated that at least some members of the MAPK family are involved in the neuroprotective effect of imipramine.

Effect of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) on learning and memory impairment and hippocampal apoptosis induced by intracerebroventricular administration of streptozotocin in rats.

Intracerebroventricular (icv) administration of streptozotocin (STZ) has been used as a metabolic model of sporadic Alzheimer's disease (AD). Erythropoietin (EPO) possesses neuroprotective and memory-improving effects, which might be advantageous in treating different characteristics of AD. Nevertheless, the hematopoietic effect of EPO has hindered its application as a neuroprotective agent. Previous studies have shown that a new Epo derivative called carbamylated Erythropoietin-Fc (CEPO-Fc), yield noticeable neuroprotective effects without affecting hematopoiesis. In this study, the neuroprotective effects of CEPO-Fc on icv-STZ induced memory impairment and hippocampal apoptosis were examined. Adult male Wistar rats weighing 250-300 g were used. STZ was administered on days 1 and 3 (3 mg/kg in divided doses/icv), and CEPO-Fc was administered at the dose of 5000 IU/ip/daily during days 4-14. The animals were trained in Morris water maze during days 15-17, and the memory retention test was performed on the 18th day. Following behavioral studies, the animals were sacrificed and their hippocampi isolated to determine the amounts of cleaved caspase-3 (the landmark of apoptosis). The results showed that CEPO-Fc treatment at the dose of 5000 IU/kg/ip was able to prevent the learning and memory deficit induced by icv-STZ. Western blot analysis revealed that STZ prompted the cleavage of caspase-3 in the hippocampus while pretreatment with CEPO-Fc significantly reduced the cleavage of this protein. Collectively, our findings suggest that CEPO-Fc could restore STZ-induced learning and memory impairment as well as apoptosis in the hippocampal region in a rat model of sporadic AD induced by icv-STZ.

Potential role of exosome in post-stroke reorganization and/or neurodegeneration.

Currently, stroke is a common and devastating condition, which is sometimes associated with permanent cerebral damages. Although in early time after stroke, the related treatments are mainly focused on the restoration of cerebral blood flow (CBF), at the same time, some changes are commencing that continue for a long time and need to be specially noticed. Previous studies have proposed several molecular mechanisms in these post-stroke events. Exosomes are a type of vesicle, which are formed and secreted by most cells as a mean to transfer cellular constituents such as proteins, DNA and/or RNA to distant cells. Therefore, they are considered as a novel mechanism of cellular communication. Herein, we reviewed the current knowledge on cascades, which are activated after stroke and consequently lead to the reorganization and/or continuance of tissue damage and development of other disorders such as Neurodegenerative diseases (ND). Thereafter, we summarized the latest proofs about the possible participation of exosomes in transferring some components such as proteins and micro-RNAs (miRs), from the affected areas to other parts of the brain and eventually cause the above-mentioned post-stroke events.

To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling.

Accumulating evidence has reached the consensus that the balance of phosphorylation state of signaling molecules is a pivotal point in the regulation of cell signaling. Therefore, characterizing elements (kinases-phosphatases) in the phosphorylation balance are at great importance. However, the role of phosphatase enzymes is less investigated than kinase enzymes. PP2A is a member of serine/threonine protein phosphatase that its imbalance has been reported in neurodegenerative diseases. Therefore, we reviewed the superfamily of phosphatases and more specifically PP2A, its regulation, and physiological functions participate in CNS. Thereafter, we discussed the latest findings about PP2A dysregulation in Alzheimer and Parkinson diseases and possible interplay between this phosphatase and insulin signaling pathways. Finally, activating/inhibitory modulators for PP2A activity as well as experimental methods for PP2A study have been reviewed.