Journal of chemical neuroanatomy最新文献

Objective

To investigate the effect and mechanism of Tetramethylpyrazine (TMP) in treating Spinal Cord Injury (SCI) using network pharmacology analysis and animal experiments.

Methods

This study was based on public databases, including PharmMapper, BATMAN-TCM, and STRING, as well as KEGG pathway analysis and other methods of network pharmacology were used to preliminarily explore the molecular mechanism of TMP in the treatment of SCI. Using a mouse SCI compression injury model, the efficacy of TMP was evaluated, and the expression of predictive targets on the PI3K/AKT and MAPK signaling pathways was measured using Western blotting and q-PCR.

Results

Network pharmacology analysis showed that TMP may exert therapeutic effects through the MAPK and PI3K/AKT signaling pathways. In animal experimental validation studies, it was shown that after treatment with TMP, the hind limb motor function scores and ramp test scores of the TMP-treated mice improved significantly. HE staining showed that after treatment with TMP, cavities decreased, fewer glial cells proliferated, and fewer inflammatory cells infiltrated; Nielsen staining showed less neuronal loss. Western blot studies showed that compared with the model group, expression of RAS, ERK1/2, RAF1, PI3K, and p-AKT proteins in the spinal cord tissue of mice treated with high-dose TMP was significantly lower. Accordingly, q-PCR studies showed that compared with the model group, the expression levels of RAS, ERK1/2, RAF1, PI3K, and p-AKT genes in the spinal cords of mice in the high-dose TMP group were significantly lower.

Conclusion

TMP exhibits a good neuroprotective effect after SCI, which may be related to inhibition of the MAPK and PI3K/AKT signaling pathways.

Concerns about inappropriate disposal of waste into unsanitary municipal solid waste landfills around the world have been on the increase, and this poses a public health challenge due to leachate production. The neurotoxic effect of Gwagwalada landfill leachate (GLL) was investigated in male adult Wistar rats. Rats were exposed to a 10% concentration of GLL for 21 days. The control group received tap water for the same period of the experiment. Our results showed that neurobehavior, absolute body and brain weights and brain histomorphology as well as parvalbumin interneurons were severely altered, with consequent astrogliosis and microgliosis after 21 days of administrating GLL. Specifically, there was severe loss and shrinkage of Purkinje cells, with their nucleus, and severe diffused vacuolations of the white matter tract of GLL-exposed rat brains. There was severe cell loss in the granular layer of the cerebellum resulting in a reduced thickness of the layer. Also, there was severe loss of dendritic arborization of the Purkinje cells in GLL-exposed rat brains, and damage as well as reduced populations of parvalbumin-containing fast-spiking GABAergic interneurons in various regions of the brain. In conclusion, data from the present study demonstrated the detrimental effects of Gwagwalada landfill leachate on the brain which may be implicated in neuropsychological conditions.

Background

Earlier reports suggest that vitamin D3 (Vit D3) supplementation attenuates Parkinsonism in drug-induced motor deficits. Moreover, the function of Vit D3 may be optimized by co-administration with vitamin A (Vit A). In line with the synergistic interplay between vitamins, we hypothesized that the efficacy of Vit D3 to attenuate Parkinsonism in a haloperidol-induced mouse model of motor deficits would be more potent when concomitantly administered with Vit A.

Methods

Thirty-six (36) adult male mice were randomly divided into six groups of six animals each: the control group, the PD model (haloperidol-treated only group) (-D2), and four other groups treated with haloperidol together with either one or two of the following vitamin supplementations: Vit D3, Vit A, Vit D3 +VA, or bromocriptine a known PD drug respectively. Motor functions were assessed using a battery of neurobehavioral tests in experimental animals, after which brain tissues were harvested and processed for biochemical and histomorphological analysis.

Results

We recorded a significant decline in motor activity in the PD mice model treated with haloperidol alone compared to other experimental groups that received vitamin supplementations. The significant decrease in motor activity observed in the PD mice model corresponded with marked neurodegenerative features in the cytoarchitecture of the pyramidal cells in the striatum and primary motor cortex (M1). Furthermore, the haloperidol-induced PD mice model treated with Vit D3 +Vit A showed significant improvement in motor activity and attenuation of oxidative stress levels and neurodegenerative features compared to other groups treated with Vit A, Vit D3 and bromocriptine alone.

Conclusion

Altogether, our findings suggest that concomitant administration of both Vit D3 and Vit A prevents the development of Parkinsonism features in the haloperidol mouse model of motor deficit. Thus, supplementation with Vit D3 +Vit A may be a viable option for slowing the onset and progression of motor deficits.

Parkinson’s Disease (PD) is an age-dependent, incessant, dynamic neurodegenerative illness. In animal models, the administration of the dopaminergic D2 antagonist Haloperidol (HP) affects the nigrostriatal pathway, inducing catalepsy, a state of immobility like PD, bradykinesia, and akinesia. The present study investigated the neural effects of Icariin (ICA), a flavonoid derived from Herba Epimedii, against HP-induced PD in rats compared to a standard drug levodopa (L-DOPA). Twenty-four adult male rats were divided into 4 groups: the control group treated with vehicle, the 2nd group treated with HP intraperitoneally, the 3rd group treated with the same dose of HP+L-DOPA orally, and the 4th one, treated with the same dose of HP+ICA orally. All the groups were treated for fourteen consecutive days. Two days before the last dose, locomotor activity was assessed in open field and rotarod tasks. At the end of the experiment, the malondialdehyde, nitric oxide (NO), iron, glycogen synthase kinase-3beta (GSK-3β), and tyrosine hydroxylase (TH) contents, glutathione S-transferase, catalase, superoxide dismutase, activities were estimated in the midbrain. Also, cortex and midbrain monoamine contents (norepinephrine, dopamine, and serotonin) were determined. Moreover, the midbrain histopathology was detected in all treated groups. The results suggested that the neuroleptic effect of HP was completely improved by ICA. This improvement occurred by decreasing the neurotoxicity via lowering midbrain lipid peroxidation, NO, GSK-3β contents, increasing antioxidant biomarkers, TH, and recovering the treated groups' cortex and midbrain monoamines contents. In conclusion, this study suggests that ICA is a suitable treatment for Parkinson's induced by HP.

Background

Calycosin (CA), a flavonoids component, has demonstrated potential neuroprotection effects by inhibiting oxidative stress in spinal cord injury (SCI) models. This study aims to investigate the impact of combined rehabilitation training (RT) and calycosin therapy on neurological function following SCI, primarily by assessing changes in motor function recovery, neuronal survival, neuronal oxidative stress levels, and neural proliferation, in order to provide novel insights for the treatment of SCI.

Materials and Methods

The SCI model was constructed by compressing the spinal cord using vascular clamps. Calycosin was injected intraperitoneally into the SCI model rats, and a group of 5 rats underwent RT. The motor function of rats after SCI was evaluated using the Basso Beattle Bresnaha (BBB) score and the inclined plate test. Histopathological changes were evaluated by NeuN immunohistochemistry, HE and Nissl staining. Apoptosis was detected by TUNEL staining. The antioxidant effect of combined treatment was assessed by measuring changes in oxidative stress markers after SCI. Western blot analysis was conducted to examine changes in Hsp90-Akt/ASK1-p38 pathway-related proteins. Finally, cell proliferation was detected by BrdU and Ki67 assays.

Results

RT significantly improved the BBB score and angle of incline promoted by calycosin, resulting in enhanced motor function recovery in rats with SCI. Combining rehabilitation training with calycosin has a positive effect on morphological recovery. Similarly, combined RT enhanced the Nissl and NeuN staining signals of spinal cord neurons increased by calycosin, thereby increasing the number of neurons. TUNEL staining results indicated that calycosin treatment reduced the apoptosis signal in SCI, and the addition of RT further reduced the apoptosis. Moreover, RT combined with calycosin reduced oxidative stress by increasing SOD and GSH levels, while decreasing MDA, NO, ROS, and LDH expressions compared to the calycosin alone. RT slightly enhanced the effect of calycosin in activating Hsp90 and Akt and inhibiting the activation of ASK1 and p38, leading to enhanced inhibition of oxidative stress by calycosin. Additionally, the proliferation indexes (Ki67 and BrdU) assays showed that calycosin treatment alone increased both, whereas the combination treatment further promoted cell proliferation.

Conclusion

Our research findings demonstrate that rehabilitation training enhances the ability of calycosin to reduce oxidative stress, resulting in a decrease in neuronal apoptosis and an increase in proliferation, ultimately promoting neuronal survival.

The striatum (Str) is injured 20 min after permanent ischemic stroke, leading to neurological deficits. Here, we aimed to explore the effect of electroacupuncture (EA) on ischemic stroke and elucidate the possible underlying mechanism. Rat permanent middle cerebral artery occlusion (pMCAO) model, EA treatment, sham-EA (SEA) treatment, beam-balance test, hematoxylin and eosin (HE) staining, Nissl staining, immunofluorescence staining, and Western blot were used to investigate the role of EA in pMCAO. The results showed that balance ability and motor coordination were obviously injured after pMCAO. EA improved balance ability and motor coordination in pMCAO rats. EA reduced striatal injury by reducing the expression of high-mobility group box 1(HMGB1)/receptor for advanced glycation end products (RAGE)/phosphorylated C-Jun N-terminal kinase (p-JNK), whereas SEA did not. Thus, EA plays a neuroprotective role during pMCAO injury, which may be related to the inhibition of HMGB1/RAGE/p-JNK expression.

Demyelinating diseases are a type of neurological disorder characterized by the damage to the myelin sheath in the central nervous system. Promoting the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) is crucial for treatment. Non-selective muscarinic receptor (MR) antagonists have been shown to improve remyelination in rodent models, although the mechanisms are still unclear. In this study, we treated cuprizone (CPZ)-induced demyelination mouse model with different concentrations of Solifenacin (Sol), a selective M3 receptor antagonist, to determine the optimal concentration for promoting remyelination. Behavioral tests and Luxol fast blue (LFB) staining were used to observe the extent of remyelination, while immunofluorescence was used to measure the expression levels of myelin-related proteins, including myelin basic protein (MBP) and platelet-derived growth factor receptor alpha (PDGFR-α). Western blot analysis was employed to analyze the expression levels of molecules associated with the Wnt/β-catenin signaling pathway. The results showed that Sol treatment significantly promoted myelin regeneration and OPCs differentiation in CPZ-induced demyelination mouse model. Additionally, Sol treatment inhibited the Wnt/β-catenin signaling pathway and reversed the effects of CPZ on OPCs differentiation. In conclusion, Sol may promote the differentiation of OPCs by inhibiting the Wnt/β-catenin signaling pathway, making it a potential therapeutic option for central nervous system demyelinating diseases.

Background

Chronic use of tramadol can cause neurotoxic effects and subsequently cause neurodegeneration in the cerebellum. The main damage mechanisms identified are oxidative stress and inflammation. Currently, we investigated the effects of coenzyme Q10 (CoQ10) in attenuates of neurodegeneration in the cerebellum induced by chronic exposure to tramadol.

Material and methods

Seventy-two male mature albino rats were allocated into four equal groups, including; non-treated group, CoQ10 group (which received CoQ10 at 200 mg/kg/day orally for three weeks), tramadol group (which received tramadol hydrochloride at 50 mg/kg/day orally for three weeks), and tramadol+CoQ10 group (which received tramadol and CoQ10 at the same doses as the previous groups). Tissue samples were obtained for stereological, immunohistochemical, biochemical, and molecular evaluations. Also, functional tests were performed to evaluate behavioral properties.

Results

We found a significant increase in stereological parameters, antioxidant factors (catalase, glutathione, and superoxide dismutase), and behavioral function scores in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). In addition, malondialdehyde levels, the density of apoptotic cells, as well as the expression of pro-inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6) and autophagy (lysosome-associated membrane protein 2, autophagy-related 5, beclin 1, and autophagy-related 12) genes were considerably reduced in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05).

Conclusion

We conclude that the administration of CoQ10 has neuroprotective effects in the cerebellum of rats that have chronic exposure to tramadol.

Background of the study

Phyllanthus amarus has high nutritional value and is beneficial in managing and treating diverse ailments. This study assessed the role of aqueous leaf extract of Phyllanthus amarus on Paraquat (PQ) induced neurotoxicity in the substantia nigra of Wistar rats.

Materials and methods

The role of aqueous leaves extract of Phyllanthus amarus was assessed using an open field test (OFT) for motor activity, oxidative stress biomarkers [Catalase (CAT), and Superoxide Dismutase (SOD)], histological examination (H and E stained) for cytoarchitectural changes and immunohistochemical studies using tyrosine hydroxylase (TH) as a marker for dopaminergic neurons. Forty-two (42) rats were categorized into six groups (n = 7); group 1: control was administered 0.5 ml/kg distilled water, group 2: received 10 mg/kg PQ + 10 mg/kg L-dopa as reference drug, group 3; received 10 mg/kg PQ, while group 4: received 10 mg/kg PQ + 200 mg/kg P. amarus, group 5: received 10 mg/kg PQ + 300 mg/kg P. amarus, and group 6: received 10 mg/kg PQ + 400 mg/kg P. amarus respectively, for 14 days. All administrations were done orally; a significant difference was set at p < 0.05.

Results and discussion

The study's open field test (OFT) revealed no motor activity deficit with Paraquat (PQ) exposure. Also, cytoarchitectural distortions were not observed with Paraquat (PQ) only treatment group compared to the control and other groups pretreated with P. amarus and L-dopa. Moreover, the Paraquat (PQ) only treatment group showed oxidative stress by significantly decreasing the antioxidant enzyme (SOD) compared to the control and L-dopa pretreated group. A significant decrease in tyrosine hydroxylase (TH) expressing dopaminergic neurons was also observed in Paraquat (PQ) only treatment. However, P. amarus treatment showed therapeutic properties by significantly increasing tyrosine hydroxylase (TH) expressing dopaminergic neuron levels relative to control.

Conclusion

Aqueous leaf extract of Phyllanthus amarus possesses therapeutic properties against Paraquat (PQ) induced changes in the substantia nigra of Wistar rats.

Gallic acid (GA) is known to be a natural phenolic compound with antioxidant and neuroprotective effects. This study aims to investigate the impact of GA against restraint stress-induced oxidative damage, anxiety-like behavior, neuronal loss, and spatial learning and memory impairment in male Wistar rats. The animals were divided into four groups (n = 8) and subjected to restraint stress for 4 h per day for 14 consecutive days or left undisturbed (control without inducing stress). In the treatment group, the animals were treated with 2 mL normal saline plus 100 mg/kg GA per day for 14 consecutive days (STR + GA group). The animals received the drug or normal saline by gavage 2 h before inducing restraint stress. ELISA assay measured oxidative stress factors. Elevated-plus maze and Morris water maze tests assessed anxiety-like behavior and spatial learning and memory, respectively. Also, neuronal density was determined using Nissl staining. Restraint stress significantly increased MDA and reduced the activities of GPX and SOD in the stressed rats, which were reserved by treatment with 100 mg/kg GA. Restraint stress markedly enhanced the anxiety-like behavior and spatial learning and memory impairment that were reserved by GA. In addition, treatment with GA reduced the neuronal loss in the stressed rats in the hippocampus and prefrontal cortex (PFC) regions. Taken together, our findings suggest that GA has the potential to be used as a good candidate to attenuate neurobehavioral disorders as well as neuronal loss in the hippocampus and PFC induced by restraint stress via reducing oxidative damage.