scholarly journals Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine

2021 ◽  
Author(s):  
Dmitriy Matveychuk ◽  
Erin M. MacKenzie ◽  
David Kumpula ◽  
Mee-Sook Song ◽  
Andrew Holt ◽  
...  
Keyword(s):  
Stress Reduction ◽  
Dopaminergic Neurons ◽  
Amine Oxidase ◽  
Neuroprotective Effects ◽  
Neural Cell Adhesion Molecules ◽  
Nitrative Stress ◽  
Reactive Aldehydes ◽  
Cord Injury ◽  
Neural Cell Adhesion ◽  
Primary Amine Oxidase

AbstractPhenelzine (PLZ) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. This multifaceted drug has a number of pharmacological and neurochemical effects in addition to inhibition of MAO, and findings on these effects have contributed to a body of evidence indicating that PLZ also has neuroprotective/neurorescue properties. These attributes are reviewed in this paper and include catabolism to the active metabolite β-phenylethylidenehydrazine (PEH) and effects of PLZ and PEH on the GABA-glutamate balance in brain, sequestration of reactive aldehydes, and inhibition of primary amine oxidase. Also discussed are the encouraging findings of the effects of PLZ in animal models of stroke, spinal cord injury, traumatic brain injury, and multiple sclerosis, as well other actions such as reduction of nitrative stress, reduction of the effects of a toxin on dopaminergic neurons, potential anticonvulsant actions, and effects on brain-derived neurotrophic factor, neural cell adhesion molecules, an anti-apoptotic factor, and brain levels of ornithine and N-acetylamino acids.

Neuroserpin in Bipolar Disorder

2020 ◽  
Vol 20 (7) ◽  
pp. 518-523
Author(s):  
Rugül Köse Çinar
Keyword(s):  
Gene Expression ◽  
Bipolar Disorder ◽  
Polymerase Chain Reaction Method ◽  
Type I ◽  
Healthy Controls ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Disease States ◽  
Cord Injury ◽  
System Functioning

Objective: Neuroserpin is a serine protease inhibitor predominantly expressed in the nervous system functioning mainly in neuronal migration and axonal growth. Neuroprotective effects of neuroserpin were shown in animal models of stroke, brain, and spinal cord injury. Postmortem studies confirmed the involvement of neuroserpin in Alzheimer’s disease. Since altered adult neurogenesis was postulated as an aetiological mechanism for bipolar disorder, the possible effect of neuroserpin gene expression in the disorder was evaluated. Methods: Neuroserpin mRNA expression levels were examined in the peripheral blood of bipolar disorder type I manic and euthymic patients and healthy controls using the polymerase chain reaction method. The sample comprised of 60 physically healthy, middle-aged men as participants who had no substance use disorder. Results: The gene expression levels of neuroserpin were found lower in the bipolar disorder patients than the healthy controls (p=0.000). The neuroserpin levels did not differ between mania and euthymia (both 96% down-regulated compared to the controls). Conclusion: Since we detected differences between the patients and the controls, not the disease states, the dysregulation in the neuroserpin gene could be interpreted as a result of the disease itself.

scholarly journals A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 539
Author(s):  
Santa Cirmi ◽  
Alessandro Maugeri ◽  
Giovanni Enrico Lombardo ◽  
Caterina Russo ◽  
Laura Musumeci ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Dopaminergic Neurons ◽  
Specific Interaction ◽  
Food Sources ◽  
Human Neuroblastoma Cell ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma ◽  
Mandarin Juice

Parkinson’s disease (PD) is a degenerative disorder of the nervous system due to unceasing impairment of dopaminergic neurons situated in the substantia nigra. At present, anti-PD drugs acting on dopamine receptors are mainly symptomatic and have only very limited neuroprotective effects, whereas drugs slowing down neurodegeneration of dopaminergic neurons and deterioration of clinical symptoms are not yet available. Given that, the development of more valuable pharmacological strategies is highly demanded. Comprehensive research on innovative neuroprotective drugs has proven that anti-inflammatory and antioxidant molecules from food sources may prevent and/or counteract neurodegenerative diseases, such as PD. The present study was aimed at the evaluation the protective effect of mandarin juice extract (MJe) against 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma cell death. Treatment of differentiated SH-SY5Y cells with 6-OHDA brought cell death, and specifically, apoptosis, which was significantly inhibited by the preincubation with MJe through caspase 3 blockage and the modulation of p53, Bax, and Bcl-2 genes. In addition, it showed antioxidant properties in abiotic models as well as in vitro, where it reduced both reactive oxygen and nitrogen species induced by 6-OHDA, along with restored mitochondrial membrane potential, and prevented the oxidative DNA damage evoked by 6-OHDA. Furthermore, MJe restored the impaired balance of SNCA, LRRK2, PINK1, parkin, and DJ-1 gene levels, PD-related factors, caused by 6-OHDA oxidative stress. Overall, these results indicate that MJe exerts neuroprotective effects against 6-OHDA-induced cell death in SH-SY5Y cells by mechanisms involving both the specific interaction with intracellular pathways and its antioxidant capability. Our study suggests a novel possible strategy to prevent and/or ameliorate neurodegenerative diseases, such as PD.

scholarly journals Sonic Hedgehog modulates the inflammatory response and improves functional recovery after spinal cord injury in a thoracic contusion–compression model

2021 ◽  
Author(s):  
Hao Zhang ◽  
Alexander Younsi ◽  
Guoli Zheng ◽  
Mohamed Tail ◽  
Anna-Kathrin Harms ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Sonic Hedgehog ◽  
Functional Recovery ◽  
Intrathecal Administration ◽  
Neuroprotective Effects ◽  
Thoracic Spinal Cord ◽  
Shh Pathway ◽  
Thoracic Spinal ◽  
Cord Injury

Abstract Purpose The Sonic Hedgehog (Shh) pathway has been associated with a protective role after injury to the central nervous system (CNS). We, therefore, investigated the effects of intrathecal Shh-administration in the subacute phase after thoracic spinal cord injury (SCI) on secondary injury processes in rats. Methods Twenty-one Wistar rats were subjected to thoracic clip-contusion/compression SCI at T9. Animals were randomized into three treatment groups (Shh, Vehicle, Sham). Seven days after SCI, osmotic pumps were implanted for seven-day continuous intrathecal administration of Shh. Basso, Beattie and Bresnahan (BBB) score, Gridwalk test and bodyweight were weekly assessed. Animals were sacrificed six weeks after SCI and immunohistological analyses were conducted. The results were compared between groups and statistical analysis was performed (p < 0.05 was considered significant). Results The intrathecal administration of Shh led to significantly increased polarization of macrophages toward the anti-inflammatory M2-phenotype, significantly decreased T-lymphocytic invasion and significantly reduced resident microglia six weeks after the injury. Reactive astrogliosis was also significantly reduced while changes in size of the posttraumatic cyst as well as the overall macrophagic infiltration, although reduced, remained insignificant. Finally, with the administration of Shh, gain of bodyweight (216.6 ± 3.65 g vs. 230.4 ± 5.477 g; p = 0.0111) and BBB score (8.2 ± 0.2 vs. 5.9 ± 0.7 points; p = 0.0365) were significantly improved compared to untreated animals six weeks after SCI as well. Conclusion Intrathecal Shh-administration showed neuroprotective effects with attenuated neuroinflammation, reduced astrogliosis and improved functional recovery six weeks after severe contusion/compression SCI.

Neuroprotective effects of granulocyte colony-stimulating factor and relationship to promotion of angiogenesis after spinal cord injury in rats

2011 ◽  
Vol 15 (4) ◽  
pp. 414-421 ◽  
Author(s):  
Junko Kawabe ◽  
Masao Koda ◽  
Masayuki Hashimoto ◽  
Takayuki Fujiyoshi ◽  
Takeo Furuya ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treated Group ◽  
Control Group ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Neuroprotective Effects ◽  
Cord Injury ◽  
Bone Marrow Derived Cells ◽  
Stimulating Factor ◽  
Angiogenic Cytokines

Object Granulocyte colony-stimulating factor (G-CSF) has neuroprotective effects on the CNS. The authors have previously demonstrated that G-CSF also exerts neuroprotective effects in experimental spinal cord injury (SCI) by enhancing migration of bone marrow–derived cells into the damaged spinal cord, increasing glial differentiation of bone marrow–derived cells, enhancing antiapoptotic effects on both neurons and oligodendrocytes, and by reducing demyelination and expression of inflammatory cytokines. Because the degree of angiogenesis in the subacute phase after SCI correlates with regenerative responses, it is possible that G-CSF's neuroprotective effects after SCI are due to enhancement of angiogenesis. The aim of this study was to assess the effects of G-CSF on the vascular system after SCI. Methods A contusive SCI rat model was used and the animals were randomly allocated to either a G-CSF–treated group or a control group. Integrity of the blood–spinal cord barrier was evaluated by measuring the degree of edema in the cord and the volume of extravasation. For histological evaluation, cryosections were immunostained with anti–von Willebrand factor and the number of vessels was counted to assess revascularization. Real-time reverse transcriptase polymerase chain reaction was performed to assess expression of angiogenic cytokines, and recovery of motor function was assessed with function tests. Results In the G-CSF–treated rats, the total number of vessels with a diameter > 20 μm was significantly larger and expression of angiogenic cytokines was significantly higher than those in the control group. The G-CSF–treated group showed significantly greater recovery of hindlimb function than the control group. Conclusions These results suggest that G-CSF exerts neuroprotective effects via promotion of angiogenesis after SCI.

The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats

1994 ◽  
Vol 80 (1) ◽  
pp. 97-111 ◽  
Author(s):  
Shlomo Constantini ◽  
Wise Young
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Body Weight Loss ◽  
Ganglioside Gm1 ◽  
Rat Spinal Cord ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Human Spinal Cord ◽  
Cord Injury ◽  
Fine Print

✓ Recent clinical trials have reported that methylprednisolone sodium succinate (MP) or the monosialic ganglioside GM1 improves neurological recovery in human spinal cord injury. Because GM1 may have additive or synergistic effects when used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat spinal cord contusion model. Spinal cord injury was caused by dropping a rod weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at T-10, which had been exposed via laminectomy. The lesion volumes were quantified from spinal cord Na and K shifts at 24 hours after injury and the results were verified histologically in separate experiments. A single dose of MP (30 mg/kg), given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56% (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity groups, respectively, compared to similarly injured control groups treated with vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to 30 mg/kg) had little or no effect on any measured variable compared to vehicle controls; when given concomitantly with MP, GM1 blocked the neuroprotective effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked these effects of MP. The effects of MP on injury-induced hyponatremia and body weight loss were also blocked by GM1. Thus, GM1 antagonized both central and peripheral effects of MP in spine-injured rats. Until this interaction is clarified, the authors recommend that MP and GM1 not be used concomitantly to treat acute human spinal cord injury. Because GM1 modulates protein kinase activity, protein kinases inhibit lipocortins, and lipocortins mediate anti-inflammatory effects of glucocorticoids, it is proposed that the neuroprotective effects of MP are partially due to anti-inflammatory effects and that GM1 antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial effects of GM1 reported in central nervous system injury may be related to the effects on neural recovery rather than acute injury processes.

scholarly journals Blood Exosomes Have Neuroprotective Effects in a Mouse Model of Parkinson’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ting Sun ◽  
Zhe-Xu Ding ◽  
Xin Luo ◽  
Qing-Shan Liu ◽  
Yong Cheng
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Amino Acid ◽  
Dopaminergic Neurons ◽  
Motor Coordination ◽  
Oxidized Lipids ◽  
Metabolomic Analysis ◽  
Neuroprotective Effects ◽  
And Control

Parkinson’s disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.

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