Journal of chemical neuroanatomy最新文献

Background

Ischemic stroke (IS) is a life-threatening neurological disease with various pathological mechanisms. Tetrahydropiperine (THP) is a natural alkaloid with protective effects against multiple diseases, such as seizure, and pain. This study was to examine the impact of THP on IS and investigate its potential mechanism.

Material and methods

We employed network pharmacology and molecular docking techniques to identify the target proteins of THP for intervention in IS. Adult male Sprague-Dawley rats were used to create a permanent middle cerebral artery occlusion model. PC-12 cells were chosen to establish an oxygen–glucose deprivation (OGD) cell model. Disease modeling followed by nimodipine (NIMO); 3-methyladenine (3-MA) and rapamycin (RAP) interventions. Open field test, Longa score, balance beam test, and forelimb grip test were used to measure motor and neurological functions. The degree of neurological damage recovery was assessed through behavioral analysis, and cerebral infarction volume was determined using TTC staining. Morphological changes were examined through HE and Nissl staining, and ultrastructural changes in neurons were observed using transmission electron microscopy. The protein expression of autophagy and related pathways was analyzed through Western blot (WB). The appropriate hypoxia time and drug concentration were determined using CCK-8 assay, which also measured cell survival rate.

Results

The network pharmacology findings indicated that the impact of THP on IS was enhanced in the PI3K/Akt signaling pathway. THP demonstrated robust docking capability with proteins associated with the autophagy and PI3K/Akt/mTOR, as indicated by the molecular docking outcomes. THP significantly improved behavioral damage, reduced the area of cerebral infarction, ameliorated histopathological damage from ischemia, increase neuronal survival, and alleviated ultrastructural damage in neurons (P < 0.05). THP enhanced the survival of PC-12 cells induced by OGD and ameliorated the morphological harm to the cells (P < 0.05). THP was found to elevate the quantities of P62, LC3-Ⅰ, PI3K, P-AKt/Akt, and P-mTOR/mTOR proteins while reducing the levels of Atg7 and Beclin1 proteins. The results of transmission electron microscopy showed no autophagosomes in the THP, 3-MA, and 3-MA + THP groups.

Conclusion

The activation of the PI3K/Akt/mTOR signaling pathway by THP inhibits autophagy and provides relief from neurological damage in IS.

The transmission of signals to the cell body from injured axons induces significant alterations in primary sensory neurons located in the ganglion tissue, the site of the perikaryon of the affected nerve fibers. Disruption of the continuity between the proximal and distal ends leads to substantial adaptability in ganglion cells and induces macrophage-like activity in the satellite cells. Research findings have demonstrated the plasticity of satellite cells following injury. Satellite cells work together with sensory neurons to extend the interconnected surface area in order to permit effective communication. The dynamic cellular environment within the ganglion undergoes several alterations that ultimately lead to differentiation, transformation, or cell death. In addition to necrotic and apoptotic cell morphology, phenomena such as histomorphometric alterations, including the development of autophagic vacuoles, chromatolysis, cytosolic degeneration, and other changes, are frequently observed in cells following injury. The use of electron microscopic and stereological techniques for assessing ganglia and nerve fibers is considered a gold standard in terms of investigating neuropathic pain models, regenerative therapies, some treatment methods, and quantifying the outcomes of pharmacological and bioengineering interventions. Stereological techniques provide observer-independent and reliable results, which are particularly useful in the quantitative assessment of three-dimensional structures from two-dimensional images. Employing the fractionator and disector techniques within stereological methodologies yields unbiased data when assessing parameters such as number. The fundamental concept underlying these methodologies involves ensuring that each part of the structure under evaluation has an equal opportunity of being sampled. This review describes the stereological and histomorphometric evaluation of dorsal root ganglion neurons and satellite cells following nerve injury models.

Objective

To test the protective effects of Garcinia kola and curcumin on the ganglion tissues of diabetic rats following the use of autologous vein graft in peripheral nerve transection injury.

Methods

The sciatic nerve on the right side was transected, and anastomosis was performed between the proximal and distal ends using an autologous vein graft. Curcumin and Garcinia kola seed extract were administered daily by oral gavage. The ganglion tissues were harvested after a 90-day waiting period. Sensory neurons in the dorsal root ganglion at the L4 and L5 levels were used for stereological evaluations. Mean sensory neuron numbers were analyzed using a stereological technique. The size of the light and dark neurons was also estimated, and ultrastructural and immunohistochemical evaluations were performed.

Results

A statistically significant difference in sensory neuron numbers was observed between the groups with and without Garcinia kola and curcumin applications. The immunohistochemical results showed that the s-100 protein is expressed selectively between cell types.

Conclusion

The results of this study show that curcumin and Garicinia kola prevented sensory neuron loss in diabetic rats following transection injury to the sciatic nerve.

Cerebral ischemia is a life-threatening health concern that leads to severe neurological complications and fatalities worldwide. Although timely intervention with clot-removing agents curtails serious post-stroke neurological dysfunctions, no effective neuroprotective intervention is available for addressing post-recanalization neuroinflammation. Herein, for the first time we studied the effect of oxyberberine (OBB), a derivative of berberine, on transient middle cerebral artery occlusion (MCAO)-generated neurological consequences in Sprague-Dawley rats. The MCAO-operated rats exhibited significant somatosensory and sensorimotor dysfunctions in adhesive removal, foot fault, paw whisker, and rotarod assays at 1 and 3 days post-surgery. These MCAO-generated neurological deficits were prevented in OBB-treated (50 and 100 mg/kg) rats, and also coincided with a smaller infarct area (in 2,3,5-triphenyl tetrazolium chloride staining) and decreased neuronal death (in cresyl violet staining) in the ipsilateral hemisphere of these animals. The immunostaining of neuronal nuclear protein (NeuN) and glial-fibrillary acidic protein (GFAP) also echoes the neuroprotective nature of OBB. The increased expression of neuroinflammatory and blood-brain barrier tight junction proteins like toll-like receptor 4 (TLR4), TRAF-6, nuclear factor kappa B (NF-κB), pNF-κB, nNOS, ASC, and IKBα in the ipsilateral part of MCAO-operated rats were restored to normal following OBB treatment. We also observed the decline in plasma levels/mRNA transcription of TNF-α, IL-1β, NLRP3, IL-6, and matrix metalloproteinase-9 and increased expression of occludin and claudin in OBB-treated rats. These outcomes imply that OBB may prevent the MCAO-induced neurological consequences and neuroinflammation by interfering with TLR4 and NLRP3 signaling in rats.

Parkinson's disease (PD), a widespread neurodegenerative disorder, often coexists with mood disorders. Degeneration of serotonergic neurons in brainstem raphe nuclei have been linked to depression and anxiety. Additionally, the locus coeruleus and its noradrenergic neurons are among the first areas to degenerate in PD and contribute to stress, emotional memory, motor, sensory, and autonomic symptoms. Another brain region of interest is habenula, which is especially related to anti-reward processing, and its function has recently been linked to PD and to mood-related symptoms. There are several neuroimaging studies that investigated role of the habenula in mood disorders. Differences in habenular size and hemispheric symmetry were found in healthy controls compared to individuals with mood disorders. The lateral habenula, as a link between the dopaminergic and serotonergic systems, is thought to contribute to depressive symptoms in PD. However, there is only one imaging study about role of habenula in mood disorders in PD, although the relationship between PD and mood disorders is known. There is little known about habenula pathology in PD but given these observations, the question arises whether habenular dysfunction could play a role in PD and the development of PD-related mood disorders. In this review, we evaluate neuroimaging techniques and studies that investigated the habenula in the context of PD and mood disorders. Future studies are important to understand habenula's role in PD patients with mood disorders. Thus, new potential diagnostic and treatment opportunities would be found for mood disorders in PD.

Physalis alkekengi L. var. franchetii (Mast.) Makino (PA), a traditional Chinese medicine, is utilised for treating dermatitis, sore throat, dysuria, and cough. This research aimed to identify the main constituents in the four extracted portions from the calyces of PA (PAC) utilising ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The Alzheimer's disease (AD) mice model was induced by D-galactose (D-gal) combined with aluminium chloride (AlCl₃). Subsequent investigation into the underlying mechanisms involved behavioural and histopathological observations. The results demonstrated that four extracted portions of PAC (PACE) significantly enhanced memory and learning abilities in the Morris water maze. The concentrations of Aβ, tau and p-tau in brain tissue exhibited a significant decrease relative to the model group. Moreover, the four PACE treatment groups increased the glutathione (GSH) and superoxide dismutase (SOD) levels, while concurrently reducing malondialdehyde (MDA), interleukin-1β (IL-1β) and interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) levels. In summary, the current study demonstrates that the four PACE formulations exhibit beneficial anti-AD properties, with the most pronounced efficacy observed in the EA group. Additionally, PAC shows potential in mitigating neuroinflammation and oxidative damage by inhibiting the TLR4/NF-κB signalling pathway. This research lays a theoretical groundwork for the future clinical development and utilisation of PAC in treating AD.

Background

Maternal diabetes during pregnancy can affect the neurological development of offspring. Glial cell-derived neurotrophic factor (GDNF), neurturin (NRTN), and neural cell adhesion molecules (NCAM) are three important proteins for brain development. Therefore, this study aimed to investigate the impacts of the mentioned neurotrophic factors in the hippocampal dentate gyrus (DG) of rat offspring born to diabetic mothers.

Methods

Wistar female rats were randomly allocated into diabetic (STZ-D) [(45 mg/kg BW, STZ (Streptozotocin), i.p)], diabetic + NPH insulin (STZ-INS) [(4–6 unit/kg/day SC)], and control groups. The animals in all groups were mated by non-diabetic male rats. Two weeks after birth, male pups from each group were sacrificed and then protein contents of GDNF, NRTN, and NCAM were evaluated using immunohistochemistry.

Results

The study found that the expression of GDNF and NRTN in the hippocampus of diabetic rat offspring was significantly higher compared to the diabetic+ insulin and control groups, respectively (P < 0.01, P < 0.001). Additionally, the expression of NCAM was significantly higher in the diabetic group the diabetic+ insulin and control groups (P < 0.01, P < 0.001).

Conclusions

The results of the study revealed that diabetes during pregnancy significantly impacts the distribution pattern of GDNF, NRTN, and NCAM in the hippocampus of rat neonates.

The involvement of consumption of high-carbohydrate high-fat (HCHF) diet in cognitive impairment is attributed, at least in part, to the activation of astrocytes, which contributes to the development of neuroinflammation, oxidative stress, and subsequent cognitive deficits. This study aimed to assess the influence of melatonin on cognitive impairment and astrogliosis induced by the HCHF diet in rats. Male Wistar rats were fed an HCHF diet for eight weeks to induce obesity and metabolic syndrome. Subsequently, they received oral melatonin treatment for four weeks at doses of 5 mg/kg, 10 mg/kg, and 30 mg/kg, alongside the HCHF diet. Cognitive function was evaluated using the Y-maze test, while the levels of proinflammatory cytokines, oxidative stress, and the number glial fibrillary acidic protein (GFAP) positive cells were assessed in the hippocampi and hypothalamus. The consumption of the HCHF diet resulted in weight gain, hyperlipidemia, impaired glucose tolerance, cognitive decline, neuroinflammation, oxidative stress damage, and astrogliosis in rats. Although melatonin treatment did not demonstrate beneficial effects on blood glucose and lipid metabolism, it improved the impaired working memory caused by the HCHF diet. Melatonin exhibited a dose-dependent reduction of astrogliosis, neuroinflammation, and lipid peroxidation while restored superoxide dismutase in the hippocampus and hypothalamus of HCHF diet-treated rats. These findings provide evidence that melatonin inhibits astrocyte activation, thereby attenuating inflammation and minimizing oxidative stress damage induced by the HCHF diet.

Organophosphorus (OP) pesticides and insecticides are used in agriculture and other industries can also cause adverse effects through environmental exposures in the people working in agricultural and pesticide industries. OP nerve agent exposures have been associated with delayed neurotoxic effects including sleep disorders, cognitive malfunctions, and brain damage in Gulf War victims, and Japanese victims of terrorist attacks with nerve agents. However, the mechanisms behind such prolonged adverse effects after chronic OP nerve agent’s exposures in survivors are not well understood. In the present study, male Wistar rats were subcutaneously exposed to nerve agent soman (0.25XLD₅₀) for 21 consecutive days to evaluate the neurobehavioral, neuropathological and biochemical alterations (oxidative stress and antioxidants levels). Neurobehavioral studies using Elevated Plus Maze (EPM), T-Maze, and rotarod tests revealed that chronic soman exposure produced alterations in behavioral functions including increased anxiety and reduction in working memory and neuromuscular strength. Biochemical studies showed that antioxidants enzyme (glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) levels were reduced and oxidative stress (reduced glutathione (GSH) and lipid peroxidation levels (malondialdehyde (MDA)) were significantly increased in brain at 30 days in soman exposed rats as compared to control rats. Neuroselective fluorojade-c stain was used to examine the brain damage after chronic soman exposure. Results demonstrated that chronic soman exposure induced neurodegeneration as brain damage was detected at 30- and 90-days post exposure. The present study results suggest that chronic nerve agent exposures even at low doses may produce long-term adverse effects like neurobehavioral deficits in rats.

Background

The pathogenesis of brain ischemic/reperfusion (I/R) insult is characterized by neuronal loss due to excessive oxidative stress responses. Ferroptosis, a form of oxidative cell death, can be triggered when the balance between antioxidants and pro-oxidants in cells is disrupted. Ozone, a natural bioactive molecule with antioxidant/anti-apoptotic and pro-autophagic properties, has been shown to enhance the antioxidant system's capacity and ameliorate oxidative stress. However, its role in neuronal ferroptosis remains unclear. Therefore, we investigated the functions and possible mechanisms of ozone in cerebral I/R-induced ferroptotic neuronal death.

Methods

A cerebral ischemia-reperfusion injury model was induced in Sprague-Dawley (SD) rats pre-treated with ozone. Intraperitoneal administration of the NRF2 inhibitor ML385, the SLC7A11 inhibitor Erastin, and the GPX4 inhibitor RSL3 was performed one hour prior to model establishment.

Results

Our results showed that ozone preconditioning mitigated neuronal damage caused by cerebral I/R, reduced the severity of neurological deficits, lowered cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats, and decreased the volume of cerebral infarcts. Transmission electron microscopy, immunofluorescence, and Western blotting indicated ferroptosis following MCAO-induced brain damage. MCAO resulted in morphological damage to neuronal mitochondria, increased lipid peroxidation accumulation, and elevated malondialdehyde (MDA) production. Furthermore, MCAO decreased levels of FTH1 and GPX4 (negative regulators of ferroptosis) and increased ACSL4 levels (a positive regulator of ferroptosis). Ozone preconditioning demonstrated a neuroprotective effect by increasing NRF2 nuclear translocation and the expression of SLC7A11 and GPX4. Treatment with ML385, Erastin, and RSL3 significantly reversed ozone preconditioning's protective effect on neuronal ferroptosis.

Conclusion

Our findings demonstrated that ozone treatment attenuates ferroptosis in a cerebral ischemia/reperfusion injury rat model via the NRF2/SLC7A11/GPX4 pathway, providing a theoretical basis for ozone's potential use as a therapy to prevent ischemic stroke.