Maternal diet supplemented with African walnuts enhances cortico-hippocampal gene expression and histomorphology in rat offspring.

BACKGROUND: The brain is built up during pregnancy. How it functions afterwards depends on how the expectant mother's diet nourishes it. Walnuts contain significant quantities of polyunsaturated fatty acids (PUFAs) and bioactive phytochemicals, which enhance brain health and function even with advancing age. This study examined the effects of a walnut-enriched diet (WED) on corticohippocampal histoarchitecture and gene expression in rat offspring. MATERIALS AND METHODS: Twenty-eight female adult Wistar rats (n= 7) averaging about 185 g in weight were used for this study. After mating, pregnant dams were split randomly into four groups: A (standard rat chow/control), B (WED from GD 0 - PND 21), C (WED from GD 0 - PND 1), D (WED from PND 1 - PND 21). Offspring of dams were sacrificed at adolescence (PND 35), with brain tissues of interest harvested for subsequent analyses. RESULTS: We observed no significant correlates in litter size, body, and brain weights across the experimental groups. Histomorphology revealed no distortion in cellular layering and delineation of cells in the PFC and dentate gyrus of both control and WED groups. Nissl staining intensity was enhanced in the offspring of dams exposed to WED versus the control, indicating improved proteostasis. Upregulated mRNA expression of DNMT3a, H2Ax, OPA1, and BDNF was observed in cortical and hippocampal tissues of WEDexposed offspring compared with the control group. CONCLUSION: A diet enriched with African walnuts during early development induced changes predictive of cognitive improvements and enhanced stress-response signalling, plasticity, and neural resilience in rat offspring.

African walnut (Tetracarpidium conophorum) extract upregulates glucocerebrosidase activity and circumvents Parkinsonian changes in the Hippocampus via the activation of heatshock proteins.

BACKGROUND: Neurodegenerative illnesses like Parkinson's and Alzheimer's are largely caused by the accumulation of aggregated proteins. Heat shock proteins (HSPs), which are molecular chaperons, have been linked with the modulation of ß-glucocerebrosidase (GCase) function encoded by GBA1 and Synucleinopathies. Herein, the chaperonic properties of African walnut ethanolic extract (WNE) in manganese-induced Parkinsonian neuropathology in the hippocampus was examined. METHODOLOGY: 48 adult male rats weighing 185 g ± 10 g were randomly assigned into 6 (A - F) groups (n = 8) and treated orally as follows: A-PBS (1 ml daily for 28 days), B-WNE (200 mg/kg daily for 28 days), C- WNE (400 mg/kg daily for 28 days), D-Mn (100 mg/kg daily for 28 days), E-Mn plus WNE (100 mg/kg Mn + 200 mg/kg WNE daily concomitantly for 28 days), F-Mn plus WNE (100 mg/kg Mn + 400 mg/kg WNE daily concomitantly for 28 days). RESULTS: Rats treated with WNE showed increased levels of HSP70 and HSP90 in comparison with the Mn-intoxicated group. GCase activity also increased significantly in animals treated with WNE. Our results further revealed the therapeutic tendencies of WNE against Mn toxicity by modulating oligomeric α-synuclein levels, redox activity, and glucose bioenergetics. Furthermore, immunohistochemical evaluation revealed reduced expression of neurofibrillary tangles, and reactive astrogliosis following WNE treatment. CONCLUSION: The ethanolic extract of African Walnut induced the activation of HSPs and increased the expression of GBA1 gene in the hippocampus. Activated heat shock proteins suppressed neurodegenerative changes due to Manganese toxicity. WNE was also shown to modulate neuroinflammatory, bioenergetics and neural redox balance in Parkinson-like neuropathology. This study was limited to the use of crude walnut extract and the evaluation of non-motor cascades of Parkinson's disease.

Sodium azide-induced degenerative changes in the dorsolateral prefrontal cortex of rats: attenuatingmechanisms of kolaviron

Identification of therapeutic targets following neurodegeneration is of major biomedical importance. Kolaviron (Kv) is a biflavonoid complex isolated from seeds of Garcina kola - a common oral masticatory agent in Nigeria known to hold medicinal value. Therefore this study evaluated the therapeutic potential of Kv on cells of the dorsolateral prefrontal cortex (DLPFC), before or after sodium azide (NaN3)-induced neurodegeneration. Rats were randomly assigned into 5 groups (6 each) and treated daily (orally) as follows: 1 ml of corn-oil (vehicle of Kv, 21 days); Kv only (200 mg/kg) for 21 days; NaN3 only (20 mg/kg for 5 days); NaN3 (20 mg/kg for 5 days) followed by Kv (200 mg/kg for 21 days); Kv (200 mg/kg for 21 days) followed by NaN3 (20 mg/kg for 5 days). After treatments, rats were sacrificed and perfused transcardially (with 4% PFA) with brains fixed in accordance with the technique to be used. The DLPFC was examined using histology (H&E), immunoperoxidase (GFAP), immunofluorescence (iNOS & nNOS) and Western blotting (MAPT, MAP2, Bax, BCL-2 and CAD). Quantitative analysis was done using ImageJ software and statistical analysis with Graphpad prism (ANOVA) at p<0.05. NaN3 treatment induced neuronal damage, characterized by reduced relative brain weight, pyknosis, karyorrhesis, astrogliosis, axonal/dendritic damage and cytoskeletal dysregualtion that subsequently resulted in increased expressions of apoptotic regulatory proteins. These degenerative changes were relatable to the observed iNOS and nNOS upregulations. However, Kv administration attenuated the NaN3- initiated destructive molecular cascades in the DLPFC of rats through mechanisms that involved inhibition of stressor molecules and toxic proteins, prevention of stress related biochemical redox, preservation of neuronal integrity, cytoskeletal framework and subsequently, reduced the level of apoptotic regulatory proteins. We conclude that Kv conferred therapeutic benefits on NaN3- induced neurodegeneration, particularly when administered before more than after the insult

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Kolaviron was protective against sodium azide (NaN3) induced oxidative stress in the prefrontal cortex.

Kolaviron is a phytochemical isolated from Garcina kola (G. kola); a common oral masticatory agent in Nigeria (West Africa). It is a bioflavonoid used--as an antiviral, anti-inflammatory and antioxidant--in relieving the symptoms of several diseases and infections. In this study we have evaluated the neuroprotective and regenerative effect of kolaviron in neurons of the prefrontal cortex (Pfc) before or after exposure to sodium azide (NaN3) induced oxidative stress. Separate groups of animals were treated as follows; kolaviron (200 mg/Kg) for 21 days; kolaviron (200 mg/Kg for 21 days) followed by NaN3 treatment (20 mg/Kg for 5 days); NaN3 treatment (20 mg/Kg for 5 days) followed by kolaviron (200 mg/Kg for 21 days); 1 ml of corn-oil (21 days-vehicle); NaN3 treatment (20 mg/Kg for 5 days). Exploratory activity associated with Pfc function was assessed in the open field test (OFT) following which the microscopic anatomy of the prefrontal cortex was examined in histology (Haematoxylin and Eosin) and antigen retrieval Immunohistochemistry to show astroglia activation (GFAP), neuronal metabolism (NSE), cytoskeleton (NF) and cell cycle dysregulation (p53). Subsequently, we quantified the level of Glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenase (LDH) in the brain tissue homogenate as a measure of stress-related glucose metabolism. Kolaviron (Kv) and Kolaviron/NaN3 treatment caused no prominent change in astroglia density and size while NaN3 and NaN3/Kv induced astroglia activation and scar formation (astrogliosis) in the Pfc when compared with the control. Similarly, Kolaviron and Kv/NaN3 did not alter NSE expression (glucose metabolism) while NaN3 and NaN3/Kv treatment increased cortical NSE expression; thus indicating stress related metabolism. Further studies on enzymes of glucose metabolism (G6PDH and LDH) showed that NaN3 increased LDH while kolaviron reduced LDH in the brain tissue homogenate (P < 0.001). In addition kolaviron treatment before (P < 0.001) or after (P < 0.05) NaN3 treatment also reduced LDH expression; thus supporting its role in suppression of oxidative stress. Interestingly, NF deposition increased in the Pfc after kolaviron treatment while Kv/NaN3 showed no significant change in NF when compared with the control. In furtherance, NaN3 and NaN3/Kv caused a decrease in NF deposition (degeneration). Ultimately, the protective effect of KV administered prior to NaN3 treatment was confirmed through p53 expression; which was similar to the control. However, NaN3 and NaN3/Kv caused an increase in p53 expression in the Pfc neurons (cell cycle dysregulation). We conclude that kolaviron is not neurotoxic when used at 200 mg/Kg BW. Furthermore, 200 mg/Kg of kolaviron administered prior to NaN3 treatment (Kv/NaN3) was neuroprotective when compared with Kolaviron administered after NaN3 treatment (NaN3/Kv). Some of the observed effects of kolaviron administered before NaN3 treatment includes reduction of astroglia activation, absence of astroglia scars, antioxidation (reduced NSE and LDH), prevention of neurofilament loss and cell cycle regulation.

Effect of ethanolic extract of Khaya senegalensis on some biochemical parameters of rat kidney.

The effect of administration of ethanolic extract of Khaya senegalensis (2mg/kg body weight) on some biochemical parameters of rat kidney were investigated. Experimental animals were randomly divided into the control, those administered with the extract for 6 days and those administered with extract for 18 days, respectively. The prolonged administration of the extract resulted in significant reduction in the alkaline phosphatase activities of the kidney and its body weight ratio (P<0.05). In contrast, the same prolonged administration of the extract resulted in significant increase in the serum sodium ion concentration (P<0.05) while there was no significant difference in serum potassium ion concentration when compared to control (P>0.05). Administration of the extract for 6 days produced no significant difference from the control values in all the parameters investigated except in serum urea concentration which produced a significant increase (P<0.05). The available evidence in this study suggest that the ethanolic extract of Khaya senegalensis exerted more deleterious effect on the kidney when administered continuously over a prolonged period than a short one and this will adversely affect the functioning of the kidney.