Saffron stigma extract and crocin play an important neuroprotective role in therapeutic measures against benzo[a]pyrene-induced behavioral alterations in zebrafish.

Saffron is a well-known expensive spice, which has many pharmacological properties against a variety of ailments. Saffron stigma and leaf contain apocarotenoids and bioactive phytochemicals having therapeutic potential against human disorders. Polycyclic aromatic hydrocarbons (PAHs) are one of the most common toxins in today's aquatic environment. Benzo[a]pyrene (B[a]P), a high molecular weight PAHs prototype, and reported as a potent neurotoxicant, which is profoundly contaminating the environment. The present study investigated the therapeutic efficacy of Saffron stigma extracts and crocin, on B[a]P-induced behavioral changes, altered antioxidant activities, and neurodegeneration in zebrafish. The behavioral responses monitored through the light-dark preference test and novel tank diving test suggested that B[a]P treated zebrafish group showed alteration in anxiolytic-like behavior. Animals exhibited their native behavior when treated alone with Saffron Stigma Extract (SSE) and crocin, an apocarotenoid which also reduced the altered behavior induced by B[a]P. The SSE and crocin stimulated the antioxidant activities with an accumulation of reduced glutathione and catalase enzymes, indicating a protective role against B[a]P-induced oxidative stress and behavioral deficits. The histopathological studies showed the percentage change of pyknotic cell counts in the Periventricular Gray Zone region of the Optic Tectum was 1.74 folds high in B[a]P treated animals as compared to control. Furthermore, the treatment of SSE and crocin reduced the pyknosis process induced by B[a]P-mediated neurodegeneration, possibly due to a better protective mechanism. Future studies may reveal the detailed mechanisms of action of potent SSE and crocin like bioactive compounds having neuroprotective potentials against neurodegenerative diseases.

Lactobacillus rhamnosus GG treatment potentiates ethanol-induced behavioral changes through modulation of intestinal epithelium in Danio rerio.

The gut-brain axis directly regulates the brain homeostatic environment; an imbalance in gut microbial composition following ethanol exposure is maleficent. In this context, involvement of probiotics as prophylactic intervention against ethanol-induced neurotoxicity is elusive in the literature. Therefore, the present study was aimed to determine the impact of chronic ethanol exposure on the neurobehavioral response of zebrafish and possible neuroprotection through co-supplementation of probiotic Lactobacillus rhamnosus GG (LGG). Zebrafish were divided into naive, control, ethanol (0.01% v/v), LGG, and ethanol co-supplemented with LGG groups. Neurobehavioral assessment was performed after 7 days of chronic waterborne exposure to ethanol with LGG co-supplementation followed by histopathological studies. The findings indicated that there was a clear alteration in locomotor activity and habitat preference, with animals preferentially migrating toward altered zones on exposure to ethanol. However, co-supplementation of LGG showed restoration against ethanol-induced neurobehavioral and cognitive dysfunction. Brain tissue pyknosis and intestinal epithelial disruption were significantly mitigated on LGG co-supplementation against ethanol in zebrafish. The present study provides a novel approach toward supplementation of probiotics such as LGG in modulation of gut commensal microbiota influencing zebrafish behavior. Moreover, the findings delineate the possible role of probiotics as a curative administration to counter ethanol-persuaded neurological outcomes.

Bisphenol A exposure induces neurobehavioral deficits and neurodegeneration through induction of oxidative stress and activated caspase-3 expression in zebrafish brain.

Bisphenol A (BPA) is noted for its adversative effects by inducing oxidative stress, carcinogenicity, neurotoxicity, inflammation, etc. However, the likely act of BPA in inducing neurodegenerative phenotypes remains elusive in the available literature. Hence, the present study was conducted to decipher the neurodegenerative potential of BPA in inducing Parkinson's disease like phenotypes in zebrafish. Zebrafish were subjected to chronic waterborne exposure to BPA for 56 days. Locomotor activities and neurobehavioral response were assessed by the NTDT (novel tank diving test), OFT (open field test), and LDPT (light-dark preference test). The oxidative stress markers and histopathological observation for pyknosis and chromatin condensation were carried out. Immunohistochemistry for activated caspase-3 and targeted proteins expression study was performed. The basic findings reveal that chronic BPA exposure significantly induces locomotor dysfunction through a significant decline in mean velocity and total distance traveled. As a measure of pyknosis and chromatin condensation, pyknotic and Hoechst positive neurons in telencephalon and diencephalon significantly increased by BPA exposure. A higher concentration of BPA adversely affects the neurobehavioral response, antioxidant status, and neuromorphology in zebrafish. Parkinson-relevant targeted protein expression viz. alpha-synuclein and LRRK2, were significantly upregulated, whereas tyrosine hydroxylase, NeuN, and Nurr1 were significantly downregulated in the zebrafish brain. As an indicator of cell death by apoptosis, the expression of activated caspase-3 was significantly increased in the BPA-exposed zebrafish brain. These basic results of the current study indicate that chronic waterborne exposure to BPA induces neuropathological manifestation leading to the development of motor dysfunction and Parkinsonism-like neurodegenerative phenotypes in zebrafish.

Suppression of bisphenol A-induced oxidative stress by taurine promotes neuroprotection and restores altered neurobehavioral response in zebrafish (Danio rerio).

Bisphenol A (BPA) has been documented as a mediator for a number of health effects, including inflammation, oxidative stress, carcinogenicity, and mood dysfunction. The literature on the role of BPA in inducing altered neurobehavioral response and brain morphology and plausible neuroprotective role of taurine against BPA induced oxidative stress mediated neurotoxicity is limited. Therefore, the present experimental paradigm was set for 21 days to expound the neuroprotective efficacy of taurine against BPA-induced neurotoxicity in zebrafish (Danio rerio) following waterborne exposure. Neurobehavioral studies were conducted by light-dark preference test (LDPT) and novel tank diving test (NTDT). To validate that the neuroprotective efficacy of taurine against BPA-induced neurotoxicity is associated with the modulation of the antioxidant defense system, we have conducted biochemical studies in zebrafish brain. Changes in brain morphology leading to neurobehavioral variations following co-supplementation of BPA and taurine were evaluated by Hoechst staining and cresyl violet staining (CVS) in periventricular gray zone (PGZ) of zebrafish brain. Our findings show that taurine co-supplementation significantly improved the BPA-induced altered scototaxis and explorative behavior of zebrafish. Further, BPA-induced augmented oxidative stress was considerably ameliorated by taurine co-supplementation. Subsequently, our observation also points toward the neuroprotective role of taurine against BPA-induced neuronal pyknosis and chromatin condensation in PGZ of zebrafish brain. In a nutshell, the findings of the current study show the neuroprotective efficacy of taurine against BPA-induced oxidative stress-mediated neurotoxicity. Elucidation of the underlying signaling mechanism of taurine-mediated neuroprotection would provide novel strategies for the prevention/treatment of BPA-persuaded serious neurological consequences.

Benzo[a]pyrene exposure and overcrowding stress impacts anxiety-like behavior and impairs learning and memory in adult zebrafish, Danio rerio.

Benzo[a]pyrene (B[a]P), a prototype of polycyclic aromatic hydrocarbons and ubiquitous environmental pollutant, alters neurobehavioral responses in aquatic organisms like zebrafish. Increasing organic load on water bodies causes population explosion leading to overcrowding (OC) stress. The effect of OC stress on neurobehavioral alterations remains unclear. The objective of our study is to elucidate the impact of OC stress on behavioral alterations and neurodegenerative phenotypes on exposure to B[a]P in zebrafish. We demonstrate the effects of OC stress (12 fish/L) on acute waterborne exposure to B[a]P (0.2 mg L-1 ) in adult wild zebrafish. Anxiety-like behavior, learning, and memory impairment were assayed by novel tank diving test, light/dark preference test, and T-maze test. Oxidative stress bio-markers were assayed along with histopathological changes in zebrafish brain. OC stress significantly impaired the learning ability and mood behavior by increasing the number of transition and time spent in the alter zones. Increased lipid peroxidation and protein carbonyl formation with significant decreased catalase activity and reduced glutathione level showed oxidative stress on exposure to OC stress and B[a]P. Pyknotic neuronal counts dramatically increased in periventricular grey zone of optic tectum brain region of zebrafish. Our findings showed that OC stress modulates the B[a]P-induced behavioral alterations causing learning and memory deficiency with histopathological changes in adult zebrafish brain. OC stress may act as an early risk factor for the eventual development of cognitive impairments and B[a]P exposure plays a key role in mediating both the facilitating and impairing actions of OC stress in memory processes.

Quercetin abrogates bisphenol A induced altered neurobehavioral response and oxidative stress in zebrafish by modulating brain antioxidant defence system.

Bisphenol A (BPA), a well-recognized anthropogenic xenoestrogen, has been identified as a causative agent responsible for inducing carcinogenicity, cognitive impairment, neurotoxicity, oxidative stress, etc. However, BPA-induced neurotoxicity and its possible amelioration through natural compound intervention remain elusive. The current study was performed to elucidate the neurotoxic potential of BPA in zebrafish (Danio rerio) by waterborne exposure and its possible amelioration by quercetin co-supplementation. Protective effect of quercetin against BPA-induced altered neurobehavioral response, oxidative stress and neuromorphological changes were evaluated in zebrafish brain. The present findings reveal that BPA-induced altered neurobehavioral response was ameliorated by quercetin. Biochemical studies advocate the potential therapeutic efficacy of quercetin against BPA-induced oxidative stress in zebrafish brain. Quercetin also shows neuroprotection against BPA-induced augmented neuronal pyknosis in periventricular grey zone (PGZ) of zebrafish brain. These basic findings indicate that quercetin may act as an effective intervention against BPA-induced neurotoxicity in zebrafish through down-regulation of oxidative stress.

Chronic waterborne exposure to benzo[a]pyrene induces locomotor dysfunction and development of neurodegenerative phenotypes in zebrafish.

Benzo[a]pyrene (B[a]P), a prototype of polycyclic aromatic hydrocarbons (PAHs), is an ubiquitous and notable anthropogenic toxicant. The escalating load of anthropogenic organic pollutants on water bodies and its momentous impact on aquatic life may lead to the development of potent neurodegenerative diseases. Thus, the present study was conducted on zebrafish model to address the potential role of B[a]P in inducing neurodegenerative disease like phenotypes. Waterborne B[a]P exposure was performed for a stipulated period of 21 days at a concentration of 0.4 µg/ml. Separate groups of zebrafish were subjected to methylphenidate hydrochloride (MPH: 0.15 mg/L) bath exposure to study the effect on their behaviour before B[a]P exposure. The findings of the present study advocate that chronic exposure to B[a]P significantly impairs the locomotor activity in zebrafish, which showed reduction in total distance travelled and velocity. Histopathological observation by cresyl violet staining showed that there was significant increase in pyknotic neuronal counts in the diencephalon and telencephalic region of zebrafish brain after B[a]P exposure. Protein expression study showed that there was a significant increase in α-synuclein and decrease in UCH-L1, PSEN2, Nurr1 and NeuN expression in whole brain lysate of B[a]P-exposed zebrafish. Tyrosine hydroxylase (TH), as a marker of dopaminergic neurons, was significantly reduced in the B[a]P-exposed group. MPH co-supplementation significantly ameliorated the B[a]P induced altered expression of Parkinson's relevant proteins in zebrafish brain. These findings advocate that the locomotor impairment following chronic B[a]P exposure is associated with development of neurodegenerative phenotypes typically affecting the dopaminergic system in zebrafish.

Home-Based Palliative Care Program Relieves Chronic Pain in Kerala, India: Success Realized Through Patient, Family Narratives.

An estimated 1.5 billion people across the globe live with chronic pain, and an estimated 61 million people worldwide experience unrelieved serious health-related suffering. One-sixth of the global population lives in India, where approximately 10 million people endure unrelieved serious health-related suffering. The state of Kerala is home to Pallium India, one of the most sophisticated palliative care programs in the country. This private organization in Trivandrum provides palliative and hospice care to underresourced populations and emphasizes holistic pain treatment. The current project features the pain stories of six patients who received treatment from Pallium India. Basic patient demographic information was collected, and a Pallium India staff member who was fluent in Malayalam and English asked questions about each patient's pain experience. Pain narratives illustrate the substantial impact of Pallium India's home visit program and the role of total pain assessment in delivering high-quality palliative care.

Fabrication of pluronic and methylcellulose for etidronate delivery and their application for osteogenesis.

Novel hydrogels were prepared by blending 4% (w/w) methylcellulose (MC) with various concentrations of 12, 14, 16, 18 and 20% (w/w) pluronic F127 (PF) to form injectable implant drug delivery systems. The blends formed gels using lower concentrations of PF compared to when using PF alone. Etidronate sodium (EDS) at a concentration of 4×10(-3)M was loaded into these blends for producing an osteogenesis effect. The pure gels or EDS loaded gels exhibited cytocompatibility to both the osteoblast (MC3T3-E1) and myoblast (C2C12) cell lines whereas the gels of 16PF, 18PF and 20PF were very cytotoxic to the cells. The EDS loaded gels demonstrated significantly greater alkaline phosphatase (ALP) activities compared to the pure gels. The longer exposure time periods of the samples to the cells, the greater was the ALP activity. These EDS loaded gels significantly increased proliferation of both cell lines thus indicating a bone regeneration effect. The PF/MC blends prolonged the in vitro release of EDS for more than 28 days. Based on the in vitro degradation test, the MC extensively improved the gel strength of the PF and delayed the degradation of the gels thus making them more functional for a sustained drug delivery for osteogenesis.