Antioxidant effect of Spirulina (Arthrospira) maxima in a neurotoxic model caused by 6-OHDA in the rat striatum

There is evidence to support that an impaired energy metabolism and the excessive generation of reactive oxygen species (ROS) contribute to brain injury in neurodegenerative disorders such as Parkinson’s disease (PD), whereas diets enriched in foods with an antioxidant action may modulate its progression. Several studies have proved that the antioxidant components produced by Spirulina, a microscopic blue-green alga, might prevent cell death by decreasing free radicals, inhibiting lipoperoxidation and upregulating the antioxidant enzyme systems. In our study, we investigated the protective effect of the Spirulina maxima (S. maxima) against the 6-OHDA-caused toxicity in the rat striatum. The S. maxima (700 mg/kg/day, vo) was administered for 40 days before and 20 days after a single injection of 6-OHDA (16 μg/2 μL) into the dorsal striatum. At 20-day postsurgery, the brain was removed and the striatum was obtained to evaluate the indicators of toxicity, such as nitric oxide levels, ROS formation, lipoperoxidation, and mitochondrial activity. These variables were found significantly stimulated in 6-OHDA-treated rats and were accompanied by declines in dopamine levels and motor activity. In contrast, the animals that received the chronic treatment with S. maxima had a restored locomotor activity, which is associated with the decreased levels of nitric oxide, ROS, and lipoperoxidation in the striatum, although mitochondrial functions and dopamine levels remained preserved. These findings suggest that supplementation with antioxidant phytochemicals (such as contained in S. maxima) represents an effective neuroprotective strategy against 6-OHDA-caused neurotoxicity vía free radical production to preserve striatal dopaminergic neurotransmission in vivo.     

Oligodendrogenesis from neural stem cells: Perspectives for remyelinating strategies

Mobilization of remyelinating cells spontaneously occurs in the adult brain. These cellular resources are specially active after demyelinating episodes in early phases of multiple sclerosis (MS). Indeed, oligodendrocyte precursor cells (OPCs) actively proliferate, migrate to and repopulate the lesioned areas. Ultimately, efficient remyelination is accomplished when new oligodendrocytes reinvest nude neuronal axons, restoring the normal properties of impulse conduction. As the disease progresses this fundamental process fails. Multiple causes seem to contribute to such transient decline, including the failure of OPCs to differentiate and enwrap the vulnerable neuronal axons. Regenerative medicine for MS has been mainly centered on the recruitment of endogenous self-repair mechanisms, or on transplantation approaches. The latter commonly involves grafting of neural precursor cells (NPCs) or neural stem cells (NSCs), with myelinogenic potential, in the injured areas. Both strategies require further understanding of the biology of oligodendrocyte differentiation and remyelination. Indeed, the success of transplantation largely depends on the pre-commitment of transplanted NPCs or NSCs into oligodendroglial cell type, while the endogenous differentiation of OPCs needs to be boosted in chronic stages of the disease. Thus, much effort has been focused on finding molecular targets that drive oligodendrocytes commitment and development. The present review explores several aspects of remyelination that must be considered in the design of a cell-based therapy for MS, and explores more deeply the challenge of fostering oligodendrogenesis. In this regard, we discuss herein a tool developed in our research group useful to search novel oligodendrogenic factors and to study oligodendrocyte differentiation in a time- and cost-saving manner.     

Synaptic vesicle protein 2A: basic facts and role in synaptic function

In recent years, there has been considerable interest in determining the function of synaptic vesicle protein 2A and its role as a target for antiepileptic drugs. Although it is known that synaptic vesicle protein 2A is involved in normal synaptic vesicle function, its participation in synaptic vesicle cycling and neurotransmitter release in normal and pathological conditions is unclear. However, the experimental evidence suggests that synaptic vesicle protein 2A could be a vesicular transporter, regulate synaptic exocytosis as a gel matrix, or modulate synaptotagmin‐1 activity. This review describes and discusses the participation of synaptic vesicle protein 2A in synaptic modulation in normal and pathological conditions.     

The influence of excipients on physical and pharmaceutical properties of oral lyophilisates containing a pregabalin-acetaminophen combination

Objectives: The purpose of the study was to investigate and characterize the oral lyophilisates containing the pregabalin-acetaminophen drug combination and as xcipients mannitol with microcrystalline cellulose or hydroxypropyl methylcellulose, in order to conclude upon drug-excipient interactions and their stability implications, impact of excipients on drug release and on the physicochemical and mechanical properties of the pharmaceutical formulations.

Methods: The oral tablets were made by using a Christ freeze-dryer alpha 2–4-LSC lyophilizer, and evaluated for stability, drug-excipient compatibility and homogeneity of the prepared pharmaceutical formulations. The formulations were evaluated for in vivo absorption in rabbits by histopathological exams.

Results: FTIR and thermogravimetric analyses, DLS technique, SEM and NIR-CI studies confirmed the compatibility between compounds. From the determined physical and biochemical parameters of the formulations it was established that they are stable, homogeneous, and meet the conditions for orally disintegrating tablets.

Conclusion: In the case of the investigated pharmaceutical formulations the study evidenced the assembling through physical bonds between the excipients and the ‘codrug’ complex, which do not affect the release of the bioactive compounds.     

Someone to talk to: the association of mentorship and cyberbullying with suicidality among US high school students

Objective

Suicide is the second-leading cause of death in youth. We tested whether having a mentoring relationship associated with lower risks for suicidality, particularly among youth at higher risk due to cyberbullying.

Methods

This study pooled the 2017 Youth Risk Behavior Survey (YRBS) data from five jurisdictions that asked students if there was at least one teacher or other adult in their school that they could talk with, if they have a problem (mentorship). Students self-reported cyberbullying exposure and suicidality in the past 12 months. Odds of suicidal ideation, planning, and attempts were estimated using multivariable weighted logistic regression in overall and sex-stratified stepwise models. Interactions between mentorship and cyberbullying were also tested.

Results

Of the 25,527 student respondents, 87% reported having a mentoring relationship. Mentoring relationships were associated with lower odds of suicidal ideation (aOR, 0.44; 95% CI 0.33–0.57), planning (aOR, 0.59; 95% CI 0.41–0.85), and suicide attempts (aOR, 0.42; 95% CI 0.31–0.56). Stratified analyses showed a significant interaction between cyberbullying and mentorship with suicidal attempts among males, and a near-significant association between cyberbullying and mentorship with suicidal thoughts among females. Compared to male students with no cyberbullying and no mentorship, odds of attempting suicide were lower for males with no cyberbullying and mentorship (aOR, 0.55, 95% CI 0.32–0.92), higher for males with cyberbullying and no mentorship (aOR, 7.78, 95% CI 3.47–17.47), but not significantly different for males with cyberbullying and mentoring relationships (aOR, 1.49, 95% CI 0.86–2.48). Similarly, compared with females with no cyberbullying and no mentorship, odds of having suicidal thoughts were lower for females with no cyberbullying and mentorship (aOR, 0.40, 95% CI 0.28–0.57), and higher for females with cyberbullying and no mentorship (aOR, 2.54, 95% CI 1.59–4.07).

Conclusion

School-based mentoring may mitigate risk of suicidality among adolescents and limit the toxic effects of cyberbullying.