Parthenogenetic embryonic stem cells have pluripotent differentiation potentials, akin to fertilized embryo-derived embryonic stem cells. The aim of this study was to compare the neuronal differentiation potential of parthenogenetic and fertilized embryo-derived embryonic stem cells. Before differentiation, karyotype analysis was performed, with normal karyotypes detected in both parthenogenetic and fertilized embryo-derived embryonic stem cells. Sex chromosomes were identified as XX. Immunocytochemistry and quantitative real-time PCR detected high expression of the pluripotent gene, Oct4, at both the mRNA and protein levels, indicating pluripotent differentiation potential of the two embryonic stem cell subtypes. Embryonic stem cells were induced with retinoic acid to form embryoid bodies, and then dispersed into single cells. Single cells were differentiated in N2 differentiation medium for 9 days. Immunocytochemistry showed parthenogenetic and fertilized embryo-derived embryonic stem cells both express the neuronal cell markers nestin, βIII-tubulin and myelin basic protein. Quantitative real-time PCR found expression of neurogenesis related genes (Sox-1, Nestin, GABA, Pax6, Zic5 and Pitx1) in both types of embryonic stem cells, and Oct4 expression was significantly decreased. Nestin and Pax6 expression in parthenogenetic embryonic stem cells was significantly higher than that in fertilized embryo-derived embryonic stem cells. Thus, our experimental findings indicate that parthenogenetic embryonic stem cells have stronger neuronal differentiation potential than fertilized embryo-derived embryonic stem cells.
Research Highlights (1) The differentiation potentials of parthenogenetic and fertilized embryo-derived embryonic stem cells from mice were compared. Results were determined by measuring gene and protein levels. (2) Karyotype analysis shows parthenogenetic embryonic stem cells have a normal karyotype, carrying the female (XX) sex chromosomes. (3) Parthenogenetic embryonic stem cells derived from autologous tissue exhibit no immunological rejection and have no ethical consequences, and therefore have promising application prospects.

Ciliary neurotrophic factor is the only known neurotrophic factor that can promote differentiation of hippocampal neural progenitor cells to glial cells and neurons in adult rats. This process is similar to spontaneous differentiation. Therefore, ciliary neurotrophic factor may be involved in spontaneous differentiation of neural stem cells. To verify this hypothesis, the present study isolated neural progenitor cells from adult male rats and cultured them in vitro. Results showed that when neural progenitor cells were cultured in the absence of mitogen fibroblast growth factor-2 or epidermal growth factor, they underwent spontaneous differentiation into neurons and glial cells. Western blot and immunocytochemical staining showed that exogenous ciliary neurotrophic factor strongly induced adult hippocampal progenitor cells to differentiate into neurons and glial cells. Moreover, passage 4 adult hippocampal progenitor cells expressed high levels of endogenous ciliary neurotrophic factor, and a neutralizing antibody against ciliary neurotrophic factor prevented the spontaneous neuronal and glial differentiation of adult hippocampal progenitor cells. These results suggest that the spontaneous differentiation of adult hippocampal progenitor cells is mediated partially by endogenous ciliary neurotrophic factor.
Research Highlights (1) Late stage neural stem cells expressed high levels of ciliary neurotrophic factor possibly because of active differentiation of late stage cells. (2) Spontaneous differentiation can promote endogenous ciliary neurotrophic factor expression in neural stem cells. (3) A neutralizing antibody against ciliary neurotrophic factor inhibited the spontaneous neuronal and glial differentiation of adult hippocampal progenitor cells, indicating endogenous ciliary neurotrophic factor participates in triggering and/or maintaining spontaneous differentiation of neural progenitor cells.

Collagen protein is an ideal scaffold material for the transplantation of neural stem cells. In this study, rat neural stem cells were seeded into a three-dimensional collagen gel scaffold, with suspension cultured neural stem cells being used as a control group. Neural stem cells, which were cultured in medium containing epidermal growth factor and basic fibroblast growth factor, actively expanded and formed neurospheres in both culture groups. In serum-free medium conditions, the processes extended from neurospheres in the collagen gel group were much longer than those in the suspension culture group. Immunofluorescence staining showed that neurospheres cultured in collagen gels were stained positive for nestin and differentiated cells were stained positive for the neuronal marker βIII-tubulin, the astrocytic marker glial fibrillary acidic protein and the oligodendrocytic marker 2′,3′-cyclic nucleotide 3′-phosphodiesterase. Compared with neurospheres cultured in suspension, the differentiation potential of neural stem cells cultured in collagen gels increased, with the formation of neurons at an early stage. Our results show that the three-dimensional collagen gel culture system is superior to suspension culture in the proliferation, differentiation and process outgrowth of neural stem cells.
Research Highlights (1) The effect of collagen gels on the process outgrowth of neural stem cells was observed in this study. The results confirmed that neural stem cells could be passaged in a three-dimensional collagen gel scaffold. (2) After culture for 4, 7, and 14 days, the neural stem cells cultured in a three-dimensional collagen gel or in suspension were selected for induced differentiation experiments, which showed that three-dimensional collagen gel scaffolds can promote the differentiation of neural stem cells into neurons.

A rat model of acute ocular hypertension was established by enhancing the perfusion of balanced salt solution in the anterior chamber of the right eye. Minocycline (90 mg/kg) was administered intraperitoneally into rats immediately after the operation for 3 consecutive days. Immunofluorescence, western blot assay and PCR detection revealed that the expression of the precursor form of nerve growth factor, nerve growth factor and the p75 neurotrophin receptor, and the mRNA expression of nerve growth factor and the p75 neurotrophin receptor, increased after acute ocular hypertension. The number of double-labeled CD11B- and precursor form of nerve growth factor-positive cells, glial fibrillary acidic protein- and p75 neurotrophin receptor-positive cells, glial fibrillary acidic protein- and caspase-3-positive cells in the retina markedly increased after acute ocular hypertension. The above-described expression decreased after minocycline treatment. These results suggested that minocycline inhibited the increased expression of the precursor form of nerve growth factor in microglia, the p75 neurotrophin receptor in astroglia, and protected cells from apoptosis.
Research Highlights (1) Retinal microglia are an important source of the retinal precursor form of nerve growth factor after acute ocular hypertension. (2) Retinal astroglial apoptosis after acute ocular hypertension was associated with the increased expression of the precursor form of nerve growth factor and the p75 neurotrophin receptor. (3) The neuroprotective effect of minocycline was due to the inhibiting effect of the precursor form of nerve growth factor and the p75 neurotrophin receptor.

Oligodendrocyte lineage gene-1 expressed in oligodendrocytes may trigger the repair of neuronal myelin impairment, and play a crucial role in myelin repair. Hypoxia-inducible factor 1α, a transcription factor, is of great significance in premature infants with hypoxic-ischemic brain damage. There is little evidence of direct regulatory effects of hypoxia-inducible factor 1α on oligodendrocyte lineage gene-1. In this study, brain slices of Sprague-Dawley rats were cultured and subjected to oxygen-glucose deprivation. Then, slices were transfected with hypoxia-inducible factor 1α or oligodendrocyte lineage gene-1. The expression levels of hypoxia-inducible factor 1α and oligodendrocyte lineage gene-1 were significantly up-regulated in rat brains prior to transfection, as detected by immunohistochemical staining. Eight hours after transfection of slices with hypoxia-inducible factor 1α, oligodendrocyte lineage gene-1 expression was upregulated, and reached a peak 24 hours after transfection. Oligodendrocyte lineage gene-1 transfection induced no significant differences in hypoxia-inducible factor 1α levels in rat brain tissues with oxygen-glucose deprivation. These experimental findings indicate that hypoxia-inducible factor 1α can regulate oligodendrocyte lineage gene-1 expression in hypoxic brain tissue, thus repairing the neural impairment.
Research Highlights (1) Brain slices in premature rats were subjected to oxygen-glucose deprivation to generate human brain slice culture models of premature infants with hypoxic-ischemic brain damage. (2) The expression levels of hypoxia-inducible factor 1α and oligodendrocyte lineage gene-1 were dynamically observed in a broader attempt to explore their expression during hypoxic-ischemic brain damage and their roles in nerve repair. (3) Hypoxia-inducible factor 1α can regulate oligodendrocyte lineage gene-1 in hypoxic brain tissue, thus repairing the neural impairment.

This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2-72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. Results revealed that at 2 hours after cerebral contusion and laceration injury, aquaporin 4 expression significantly increased, brain water content and blood-brain barrier permeability increased, and the number of pinocytotic vesicles in cerebral microvascular endothelial cells increased. In addition, the mitochondrial accumulation was observed. As contusion and laceration injury became aggravated, aquaporin 4 expression continued to increase, brain water content and blood-brain barrier permeability gradually increased, brain capillary endothelial cells and astrocytes swelled, and capillary basement membrane injury gradually increased. The above changes were most apparent at 12 hours after injury, after which they gradually attenuated. Aquaporin 4 expression positively correlated with brain water content and the blood-brain barrier index. Our experimental findings indicate that increasing aquaporin 4 expression and blood-brain barrier permeability after cerebral contusion and laceration injury in humans is involved in the formation of brain edema.
Research Highlights (1) Aquaporin 4 expression, brain water content, and blood-brain barrier index were upregulated at early stages following cerebral contusion and laceration injury in humans. (2) Aquaporin 4 expression positively correlated with brain water content and blood-brain barrier permeability at early stages following cerebral contusion and laceration injury in humans.

This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged ≥ 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions: anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only (partial coefficient = 0.453, P = 0.045), after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.661, P = 0.001) and between the left prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.573, P = 0.004) in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.
Research Highlights (1) Automatic MRI volumetry is an accurate method to quantify regional brain atrophy in stroke patients. (2) The standardized volume of the left dorsolateral prefrontal cortex correlated positively with the performance of semantic verbal fluency test at 3 and 15 months poststroke in both elderly male and female patients. (3) In elderly patients with ischemic stroke, performance on executive function and semantic verbal fluency tests did not correlate with location of infarcts, regional brain atrophy or white matter lesions. (4) These results suggest that sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in elderly patients with stroke.

Previous studies have demonstrated that reactions to unfair offers in the ultimatum game are correlated with negative emotion. However, little is known about the difference in neural activity between a proposer's decision-making in the ultimatum game compared with the dictator game. The present functional magnetic resonance imaging study revealed that proposing fair offers in the dictator game elicited greater activation in the right supramarginal gyrus, right medial frontal gyrus and left anterior cingulate cortex compared with proposing fair offers in the ultimatum game in 23 Chinese undergraduate and graduate students from Beijing Normal University in China. However, greater activation was found in the right superior temporal gyrus and left cingulate gyrus for the reverse contrast. The results indicate that proposing fair offers in the dictator game is more strongly associated with cognitive control and conflicting information processing compared with proposing fair offers in the ultimatum game.
Research Highlights (1) The current functional magnetic resonance imaging findings reveal that the pattern of neural activity underlying fair behavior mainly driven by a tendency to fairness differs from that underlying fair behavior mainly driven by strategic motivations. (2) The results indicate that proposing fair offers in the dictator game is more closely associated with cognitive control and conflicting information processing compared with proposing fair offers in the ultimatum game.

Distribution and activity of mitochondria are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5′-triphosphate production is regulated by many control mechanism-firstly by oxygen, substrate level, adenosine-5′-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by “second control mechanisms,” such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, allosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5′-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria, similarly, decline of antioxidative enzyme activities (e.g. in the elderly) enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.
Research Highlights (1) Regulation of cellular bioenergetics is crucial in processes of neuroplasticity and neurotoxicity. (2) Mitochondrial oxidative phosphorylation is the most important source of cellular energy in the form of adenosine-5'-triphosphate. (3) The adenosine-5'-triphosphate production is regulated primarily by oxygen, substrate level, adenosine-5'-diphosphate level, mitochondrial membrane potential, rate of coupling and proton leak. (4) This review article focuses on the mitochondrial processes related to neuroplasticity, control of oxidative phosphorylation and production of reactive oxygen species. (5) The regulatory mechanisms of cellular bioenergetics are summarized with aim to better understand the function, physiology as well as pathophysiology of various diseases, including neurodegenerative and psychiatric disorders.

Most hypotheses concerning the mechanisms underlying Parkinson's disease are based on altered synaptic transmission of the nigrostriatal system. However, extrasynaptic transmission was recently found to affect dopamine neurotransmitter delivery by anisotropic diffusion in the extracellular matrix, which is modulated by various extracellular matrix components such as fibronectin. The present study reviewed the neuroprotective effect of fibronectin in extrasynaptic transmission. Fibronectin can regulate neuroactive substance diffusion and receptor activation, and exert anti-neuroinflammatory, adhesive and neuroprotective roles. Fibronectin can bind to integrin and growth factor receptors to transactivate intracellular signaling events such as the phosphatidylinositol 3-kinase/protein kinase B pathway to regulate or amplify growth factor-like neuroprotective actions. Fibronectin is assembled into a fibrillar network around cells to facilitate cell migration, molecule and ion diffusion, and even drug delivery and treatment. In addition, the present study analyzed the neuroprotective mechanism of fibronectin in the pathogenesis of Parkinson's disease, involving integrin and growth factor receptor interactions, and discussed the possible therapeutic and diagnostic significance of fibronectin in Parkinson's disease.
Research Highlights (1) This study reviewed the neuroprotective effect of fibronectin, a major extracellular matrix component, in extrasynaptic transmission and its possible therapeutic and diagnostic significance for Parkinson's disease. (2) Evidence showed that fibronectin can bind to integrins and growth factor receptors (such as insulin-like growth factor 1 receptor) to transactivate intracellular signaling events, such as the phosphatidylinositol 3-kinase/protein kinase B pathway, and regulate or amplify growth factor-like neuroprotective actions.