G-protein-coupled receptor 17 (GPR17), an originally orphan receptor, was identified as a new uracil nucleotides/cysteinyl leukotriene receptor. However, whether GPR17 is really classified as a leukotriene receptor is a matter deserving further investigation. GPR17 is involved in many physiological and pathological processes including brain injury, spinal cord injury, and oligodendrocyte differentiation. GPR17 may become a new therapeutic target in these diseases. In this article, the research progress on the pharmacology and pathophysiological roles of GPR17 is reviewed.
Central Nervous System ; injuries ; physiopathology ; Humans ; Neurogenesis ; physiology ; Receptors, G-Protein-Coupled ; metabolism ; physiology

Astrocytes can regulate synaptic transmission by releasing gliotransmitter, and also can promote synaptogenesis and neurogenesis by releasing estrogen, thrombospondins, IL-1beta and IL-6. Astrocytes may play critical roles in neural nutrition and neuroprotection, so that it might be a new target for treatment of certain central nervous system diseases.
Astrocytes ; physiology ; Estrogens ; metabolism ; Humans ; Interleukin-1beta ; metabolism ; Neurogenesis ; physiology ; Neurons ; physiology ; Neurotransmitter Agents ; metabolism ; Synaptic Transmission ; physiology ; Thrombospondins ; metabolism

Neurologic deficits resulting from stroke remain largely intractable, which has prompted thousands of studies aimed at developing methods for treating these neurologic sequelae. Endogenous neurogenesis is also known to occur after brain damage, including that due to cerebral infarction. Focusing on this process may provide a solution for treating neurologic deficits caused by cerebral infarction. The phosphatidylinositol-3-kinase (PI3K) pathway is known to play important roles in cell survival, and many studies have focused on use of the PI3K pathway to treat brain injury after stroke. Furthermore, since the PI3K pathway may also play key roles in the physiology of neural stem cells (NSCs), eliciting the appropriate activation of the PI3K pathway in NSCs may help to improve the sequelae of cerebral infarction. This review describes the PI3K pathway, its roles in the brain and NSCs after cerebral infarction, and the therapeutic possibility of activating the pathway to improve neurologic deficits after cerebral infarction.
Brain Injuries ; Brain* ; Cell Survival ; Cerebral Infarction* ; Neural Stem Cells* ; Neurogenesis ; Neurologic Manifestations ; Physiology ; Regeneration* ; Stroke

As a major cause of disability, depression is expected to become the second highest burden of disease worldwide by the year 2020. The shift of research in depression from monoamine hypothesis to the realm of neurotrophic hypothesis, neural plasticity hypothesis, and enhancing neurogenesis as an antidepressant-like agent brings about crucial insights to find novel mediator of antidepressant activity. Studies have shown that the neuropeptide VGF participates in the regulation of hippocampal neurogenesis and neuroplasticity and also plays an important role in the regulation of neuronal proliferation and survival, suggesting that the neuropeptide VGF may be a novel regulator in antidepressant treatment. The authors review the latest progress in the regulatory mechanisms of neuropeptide VGF on neurogenesis, neurotrophic and synaptic activity in depression. Further understanding of the role of neuropeptide VGF in depression can identify novel targets for pharmacological interventions.
Animals ; Antidepressive Agents ; Depression ; physiopathology ; Humans ; Neurogenesis ; Neuropeptides ; physiology ; Synaptic Transmission

Traumatic brain injury (TBI) is a major cause of mortality and morbidity in the world. Recent clinical investigations and basic researches suggest that strategies to improve angiogenesis following TBI may provide promising opportunities to improve clinical outcomes and brain functional recovery. More and more evidences show that circulating endothelial progenitor cells (EPCs), which have been identified in the peripheral blood, may play an important role in the pathologic and physiological angiogenesis in adults. Moreover, impressive data demonstrate that EPCs are mobilized from bone marrow to blood circulation in response to traumatic or inflammatory stimulations. In this review, we discussed the role of EPCs in the repair of brain injury and the possible therapeutic implication for functional recovery of TBI in the future.
Blood-Brain Barrier ; Brain Injuries ; physiopathology ; therapy ; Endothelial Cells ; cytology ; Humans ; Neurogenesis ; Stem Cells ; physiology

Stem cells are emerging as therapeutic candidates in a variety of diseases because of their multipotent capacities. Among these, mesenchymal stem cells (MSCs) derived from bone marrow, umbilical cord blood or adipose tissue, comprise a population of cells that exhibit extensive proliferative potential and retain the ability to differentiate into multiple tissue-specific lineage cells including osteoblasts, chondrocytes, and adipocytes. MSCs have also been shown to enhance neurological recovery, although the therapeutic effects seem to be derived from an indirect paracrine effect rather than direct cell replacement. MSCs secrete neurotrophic factors, promote endogenous neurogenesis and angiogenesis, encourage synaptic connection and remyelination of damaged axons, decrease apoptosis, and regulate inflammation primarily through paracrine actions. Accordingly, MSCs may prevail as a promising cell source for cell-based therapy in neurological diseases.
Cell Differentiation/physiology ; Clinical Trials as Topic ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/*cytology/physiology ; Models, Biological ; Nervous System Diseases/metabolism/*therapy ; Neurogenesis/physiology ; Tissue Therapy/methods

Vascular endothelial growth factor (VEGF) was originally recognized as a substance predominantly with vascular permeability and angiogenesis. Recently, more and more evidence indicated that VEGF is expressed in the neurons of the developing and adult brains. Functional investigation demonstrated that VEGF shows several important effects on the neuronal development and physiological function. For example, VEGF accelerates the development of neurons and neural dendritic and axon growth. Besides, VEGF directly and acutely regulates the functions of multiple ion channels of the neuron membrane and changes neural excitability. In traumatic or ischemic injured brains, VEGF produces neuroprotection, enhances capacity of adult neurogenesis and transformation of astroglial cells into new neurons, which are fundamental basis for re-establishment of neural network. Based on the knowledge obtained from the literatures, we propose that VEGF may play very important roles in neural plasticity in the normal brain, and the reconstruction of neurovascular units and neural repair in the traumatic injured brain. This review mainly focuses on neural activity and repair roles of VEGF in adult mammalian brains. Further study on the mechanism of VEGF's neurobiological effects in the brain will be helpful for understanding the regulation of brain functions and developing new therapeutic strategy for prevention of neurodegeneration of the brain.
Animals ; Astrocytes ; cytology ; Brain Injuries ; physiopathology ; Humans ; Neurogenesis ; Neuronal Plasticity ; Neurons ; cytology ; Vascular Endothelial Growth Factor A ; physiology

Chronic stress impairs radial neural stem cell (rNSC) differentiation and adult hippocampal neurogenesis (AHN), whereas promoting AHN can increase stress resilience against depression. Therefore, investigating the mechanism of neural differentiation and AHN is of great importance for developing antidepressant drugs. The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against depression. However, whether CBD can modulate rNSC differentiation and hippocampal neurogenesis is unknown. Here, by using the chronic restraint stress (CRS) mouse model, we showed that hippocampal rNSCs mostly differentiated into astrocytes under stress conditions. Moreover, transcriptome analysis revealed that the FoxO signaling pathway was involved in the regulation of this process. The administration of CBD rescued depressive-like symptoms in CRS mice and prevented rNSCs overactivation and differentiation into astrocyte, which was partly mediated by the modulation of the FoxO signaling pathway. These results revealed a previously unknown neural mechanism for neural differentiation and AHN in depression and provided mechanistic insights into the antidepressive effects of CBD.
Animals ; Cannabidiol/pharmacology* ; Cell Differentiation ; Depression/prevention & control* ; Hippocampus/metabolism* ; Humans ; Mice ; Neural Stem Cells ; Neurogenesis/physiology*

OBJECTIVETo review the main neuropsychiatric disorders and cognitive deficits in patients with Cushing's disease (CD) and the associated pathophysiological mechanisms underlying CD. These mechanistic details may provide recommendations for preventing or treating the cognitive impairments and mood disorders in patients with CD.

DATA SOURCESData were obtained from papers on psychiatric and cognitive complications in CD published in English within the last 20 years. To perform the PubMed literature search, the following keywords were input: cushing's disease, cognitive, hippocampal, or glucocorticoids.

STUDY SELECTIONStudies were selected if they contained data relevant to the topic addressed in the particular section. Because of the limited length of this article, we have frequently referenced recent reviews that contain a comprehensive amalgamation of literature rather than the actual source papers.

RESULTSPatients with active CD not only suffer from many characteristic clinical features, but also show some neuropsychiatric disorders and cognitive impairments. Among the psychiatric manifestations, the common ones are emotional instability, depressive disorder, anxious symptoms, impulsivity, and cognitive impairment. Irreversible effects of previous glucocorticoid (GC) excess on the central nervous system, such as hippocampal and the basal ganglia, is the most reasonable reason. Excess secretion of cortisol brings much structural and functional changes in hippocampal, such as changes in neurogenesis and morphology, signaling pathway, gene expression, and glutamate accumulation. Hippocampal volume loss can be found in most patients with CD, and decreased glucose utilization caused by GCs may lead to brain atrophy, neurogenesis impairment, inhibition of long-term potentiation, and decreased neurotrophic factors; these may also explain the mechanisms of GC-induced brain atrophy and hippocampal changes.

CONCLUSIONSBrain atrophy and hippocampal changes caused by excess secretion of cortisol are thought to play a significant pathophysiological role in the etiology of changes in cognitive function and psychiatric disturbances. The exact mechanisms by which GCs induce hippocampal volume loss are not very clear till now. So, further investigations into the mechanisms by which GCs affect the brain and the effective coping strategy are essential.

Brain-Derived Neurotrophic Factor ; genetics ; Cognition Disorders ; etiology ; Glucocorticoids ; physiology ; Hippocampus ; pathology ; physiology ; Humans ; Mental Disorders ; etiology ; Neurogenesis ; Pituitary ACTH Hypersecretion ; complications ; pathology ; physiopathology ; Quality of Life ; Signal Transduction

Chronic spinal cord lesions (CSCL) which result in irreversible neurologic deficits remain one of the most devastating clinical problems. Its pathophysiological mechanism has not been fully clarified. As a crucial factor in the outcomes following traumatic spinal cord injury (SCI), the blood-spinal cord barrier (BSCB) disruption is considered as an important pathogenic factor contributing to the neurologic impairment in SCI. Vascular endothelial growth factor (VEGF) is a multirole element in the spinal cord vascular event. On one hand, VEGF administrations can result in rise of BSCB permeability in acute or sub-acute periods and even last for chronic process. On the other hand, VEGF is regarded to be correlated with angiogenesis, neurogenesis and improvement of locomotor ability. Hypoxia inducible factor-1 (HIF-1) is a primary regulator of VEGF during hypoxic conditions. Therefore, hypoxia-mediated up-regulation of VEGF may play multiple roles in the BSCB disruption and react on functional restoration of CSCL. The purpose of this article is to further explore the relationship among HIF-1, hypoxia-mediated VEGF and BSCB dysfunction, and investigate the roles of these elements on CSCL.
Animals ; Chronic Disease ; Humans ; Hypoxia-Inducible Factor 1 ; physiology ; Neovascularization, Physiologic ; Neurogenesis ; Spinal Cord ; physiopathology ; Spinal Cord Injuries ; physiopathology ; Vascular Endothelial Growth Factor A ; physiology