IGF 1, BDNF, and NGF mediate the neuro-modulatory role of stem cells in acrylamide-induced hippocampal toxic changes in rats.

BACKGROUND: Acrylamide (ACR), a common industrial chemical, is a strong neurotoxic material. The hippocampus is a brain area of interest mostly affected by Alzheimer's disease. Mesenchymal stem cells (MSCs) usefulness in various neurological diseases including Alzheimer's is being debated. In this work, the authors aim to explore the role of MSCs in ACR-induced hippocampal neurodegeneration and elucidate the mediating mechanism. MATERIALS AND METHODS: For this purpose, ten rats served as control, another ten were injected ACR (i.p. 50 mg/kg/day for 2 weeks), and the last ten rats were injected ACR in addition to MSCs (i.p. 1 × 107 MSCs single injection). RESULTS: ACR induced neurodegenerative histopathological hippocampal changes and adversely altered hippocampal oxidative stress markers SOD, MDA, and GSH. ACR had induced hippocampal demyelination as detected by silver staining. ACR significantly (P < 0.05) up-regulated the ELISA hippocampal TNF-alpha and IL-6 and produced microglial & astrocyte activation (as tracked by Iba1 & GFAP immunohistochemistry respectively). ACR significantly reduced hippocampal PCR gene expression of IGF 1 (insulin growth factor-1), BDNF (brain-derived neurotrophic factor), and NGF (nerve growth factor). MSCs administration had mitigated all the previous deleterious changes. CONCLUSIONS: Acrylamide caused detrimental effects on the hippocampus and demonstrably altered the hippocampal architecture. Bone marrow mesenchymal stem cells offered a promising therapeutic role against these neurotoxic effects of acrylamide, presumably through modulation of IGF 1, BDNF, and NGF gene expressions.

Effect of Selenium nanoparticles on Paraquat-induced-neuroinflammation and oligodendocyte modulation: Implication of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.

BACKGROUND: Paraquat (PQ), is an extensively used herbicide and is a well-established powerful neurotoxin. However, the mechanism underlying its neurotoxicity still needs further investigation. AIM OF WORK: The study investigated the pathogenesis of PQ-induced neuroinflammation of the substantia nigra pars compacta (SNPC) and cerebellum and evaluated the potential effect of selenium nanoparticles (SeN) against such neurotoxicity. METHODS: Thirty-six mice were randomly divided into three groups; Control group, PQ group: mice received PQ 10 mg/kg (i.p), and PQ + SeN group; mice received PQ in addition to oral SeN 0.1 mg/kg. All regimens were administered for 14 days. The mice's brains were processed for biochemical, molecular, histological, and immune-histochemical assessment. RESULTS: SeN increased the SNPC and cerebellum antioxidants (reduced glutathione, glutathione peroxidase, and superoxide dismutase 1) while decreasing malondialdehyde concentration. Also, SeN increased the anti-inflammatory interleukin (IL)-10 and decreased the pro-inflammatory IL-1ß and -6 along with improving the angiogenic nitric oxide and reducing caspase-1. Further, western blots of phosphorylated Janus kinase (JAK2)/signal transducer and activator of transcription3 (STAT3) proteins showed a significant decline. Those improving effects of SeN on SNPC, and cerebellum were supported by the significantly preserved dopaminergic and Purkinje neurons, the enhanced myelin fibers on Luxol fast blue staining, and the marked increase in Olig-2, Platelet-derived growth factor-alpha, and tyrosine hydroxylase immunoreactivity. CONCLUSION: SeN could mitigate PQ-induced neurotoxicity via its antioxidant, anti-inflammatory, and antiapoptotic properties.

Nano-curcumin versus curcumin in amelioration of deltamethrin-induced hippocampal damage.

We aimed to prove that oxidative stress is the main mechanism responsible for hippocampal neurotoxicity induced by deltamethrin (DLM). The protective role of curcumin (CMN) and nano-curcumin (NCMN) over this toxicity was studied. The rats were categorized into four groups: control, DLM, CMN and NCMN. The study continued for 30 days. Hippocampus was processed for histological, biochemical and immunohistochemical studies. Caspase-3, glial fibrillar acidic protein (GFAP), acetylcholinesterase (AChE), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) were measured for DLM-induced oxidative stress (increased MDA by 354%/decreased GSH by 61%, SOD by 61%, CAT 57%). Oxidative stress induced apoptosis of hippocampal neurons through increasing Nrf2, gamma-glutamyl cysteine synthetase heavy subunit (GCS-HS) and light subunit (GCS-LS) and decreasing AChE. It increases the activity of astrocytes through increasing GFAP. Finally, oxidative stress has a bad impaction on cognitive function. Improvement of oxidative stress was observed with use of CMN and NCMN (decrease of MDA/increase of GSH, SOD, CAT). The level of Nrf2, GCS-HS and GCS-LS decreased, while AChE, GFAP increased. Improvement of cognitive function was observed in both groups. In conclusion, oxidative stress is the common mechanism responsible for DLM-induced hippocampal neurotoxicity. It exerts apoptosis of hippocampal neurons through increasing Nrf2, HS-GCS, LS-GCS and decreasing AChE. In addition, it activates astrocytes through increasing expression of GFAP. The protective role of CMN and CMMN is related to their potent antioxidant effect. Much improvement has been detected with NCMN as compared to CMN.