Selenium reduces nociceptive response in acute 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced neurotoxicity.

The potential of Se to alleviate pain associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity was investigated. Swiss mice were intraperitoneally injected with MPTP (20 mg/kg) 4 times with an interval of 2 h in 1 day. Seven days after MPTP injection, the mice (n = 5 mice per group) were randomly assigned to groups: MPTP-, DOPA (50 mg/kg)-, Se4 (0.4 mg/kg)-, Se6 (0.6 mg/kg)-, DOPA+Se4-, and DOPA+Se6-treated groups were compared with controls. MPTP mice were treated for seven days; thereafter, motor-coordination and nociceptive-motor reactions were assessed. Pro-inflammatory cytokines (IL-1ß, IL-6 and TNFα), and selected pain biomarkers (substance P (SP), glutamate and ß-endorphin) were assessed in the serum and the substantial nigra pars compacta (SNpc). Motor activity was increased slightly by Se (0.6 or 0.4 mg/kg) vs. MPTP (10.48 ± 2.71 or 11.81 ± 1.28 s vs. 3.53 ± 0.06 s respectively) but considerably increased by DOPA (50 mg/kg) vs. MPTP (50.47 ± 3.06 s vs. 3.53 ± 0.06 s respectively). Se and DOPA increased nociceptive threshold but Se alone reduced both serum and SN pro-inflammatory cytokines. Se modulates SP while DOPA modulates SP and glutamate in the SNpc of mice treated with MPTP. Se suppressed pro-inflammatory cytokines and restored the basal pain biomarkers in the SNpc of mice treated with MPTP. Se requires further study as analgesic adjuvant.

Neurobehavioral, neurochemical and synaptic plasticity perturbations during postnatal life of rats exposed to chloroquine in-utero.

Despite reports that quinoline antimalarials including chloroquine (Chq) exhibit idiosyncratic neuropsychiatric effects even at low doses, the drug continues to be in widespread use during pregnancy. Surprisingly, very few studies have examined the potential neurotoxic action of Chq exposure at different points of gestation or how this phenomenon may affect neurophysiological well-being in later life. We therefore studied behavior, and the expression of specific genes and neurochemicals modulating crucial neural processes in offspring of rats exposed to prophylactic dose of Chq during different stages of gestation. Pregnant rats were injected 5 mg/kg/day (3 times) of Chq either during early- (first week), mid- (second week), late- (third week), or throughout- (all weeks) gestation, while controls received PBS injection. Behavioral characterization of offspring between postnatal days 15-20 in the open field, Y-maze, elevated plus and elevated zero mazes revealed that Chq evoked anxiogenic responses and perturbed spatial memory in rats, although locomotor activity was generally unaltered. In the prefrontal cortex (PFC), hippocampus and cerebellum of rats prenatally exposed to Chq, RT-qPCR analysis revealed decreased mRNA expression of presynaptic marker synaptophysin, which was accompanied by downregulation of postsynaptic marker PSD95. Synaptic marker PICK1 expression was also downregulated in the hippocampus but was unperturbed in the PFC and cerebellum. In addition to recorded SOD downregulation in cortical and hippocampal lysates, induction of oxidative stress in rats prenatally exposed to Chq was corroborated by lipid peroxidation as evinced by increased MDA levels. Offspring of rats infused with Chq at mid-gestation and weekly treatment throughout gestation were particularly susceptible to neurotoxic changes, especially in the hippocampus. Interestingly, Chq did not cause histopathological changes in any of the brain areas. Taken together, our findings causally link intrauterine exposure to Chq with postnatal behavioral impairment and neurotoxic changes in rats.

Frequent exposure to varied home cage sizes alters pain sensitivity and some key inflammation-related biomarkers.

BACKGROUND: Nature and size of rodent cages vary from one laboratory or country to another. Little is however known about the physiological implications of exposure to diverse cage sizes in animal-based experiments. METHOD: Here, two groups of male Swiss mice (Control group - Cage stationed, and Test group - Cage migrated) were used for this study. The cage-migrated mice were exposed daily to various cage sizes used across laboratories in Nigeria while the cage-stationed mice exposed daily to different but the same cage size and shape. At the end of the 30 days exposure, top-rated paradigms were used to profile changes in physiological behaviours, and this was followed by evaluation of histological and biochemical metrics. RESULTS: The study showed a significant (p < 0.05) decrease in blood glucose levels (at 60 and 120 min of oral glucose tolerance test) in the cage-migrated mice compared to cage-stationed mice. Strikingly, peripheral oxidative stress (plasma malondialdehyde) and pain sensitivity (formalin test, hot-and-cold plate test, and von Frey test) decreased significantly in cage-migrated mice compared to cage-stationed animals. Also, the pro-inflammation mediators (IL-6 and NF-κB) increased significantly in cage-migrated mice compared to cage-stationed mice. However, emotion-linked behaviours, neurotransmitters (serotonin, noradrenaline and GABA), brain and plasma electrolytes were not significantly difference in cage-migrated animals compared to cage-stationed mice. CONCLUSION: Taken together, these results suggest that varied size cage-to-cage exposure of experimental mice could affect targeted behavioural and biomolecular parameters of pain and inflammation, thus diminishing research reproducibility, precipitating false negative/positive results and leading to poor translational outcomes.

Chlorpyrifos- and Dichlorvos-Induced Oxidative and Neurogenic Damage Elicits Neuro-Cognitive Deficits and Increases Anxiety-Like Behavior in Wild-Type Rats.

The execution of agricultural activities on an industrial scale has led to indiscriminate deposition of toxic xenobiotics, including organophosphates, in the biome. This has led to intoxication characterized by deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to a combination of two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP), on neuro-cognitive performance and anxiety-like behaviors in rats. Thirty-two adult male Wistar rats (150⁻170 g) were randomly divided into four groups, orally exposed to normal saline (NS), DDVP (8.8 mg/kg), CPF (14.9 mg/kg), and DDVP + CPF for 14 consecutive days. On day 10 of exposure, anxiety-like behavior and amygdala-dependent fear learning were assessed using open field and elevated plus maze paradigms, respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following three training trials on days 11, 12, and 13. On day 15, the rats were euthanized, and their brains excised, with the hippocampus and amygdala removed. Five of these samples were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three were processed for histology (cresyl violet stain) and proliferative markers (Ki67 immunohistochemistry). Marked (p ≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p ≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damage are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.

Long-term spatial memory and morphological changes in hippocampus of Wistar rats exposed to smoke from Carica papaya leaves.

OBJECTIVE: To investigate the effects of smoking of dried leaves of Carica papaya (pawpaw) based on ethnopharmacological information which indicated that smoking of papaya leaves could influence motor performance and learning. METHODS: Twenty-four rats were used for the study, and were grouped into four groups. Groups 1 served as the control (not exposed to papaya leaves smoke), while Groups 2, 3 and 4 were exposed to smoke from 6.25 g, 12.50 g and 18.75 g of dry pawpaw leaves respectively in a smoking chamber twice daily for 21 d with each exposure lasting for 3 min. Lastly, hippocampus was harvested in each group for histological study. RESULTS: The results showed that there were significant (P<0.05) increases in mean of recall latencies of long-term spatial memory in the animal administered the high dose while the other groups had significantly (P<0.05) lower frequencies. Histological investigation showed signs of mild neural degeneration in high dose group and hypochromic appearance of the Nissl substance in all treated groups. CONCLUSIONS: In conclusion, the findings from this study has demonstrated that smoking of papaya leaves has the ability to maintain an intact long-term spatial memory at all doses but retrieving such memory is faster with the low and medium dosages.