Male ; Humans ; Prostatic Neoplasms ; Cell Differentiation ; Cell Lineage ; Cell Plasticity

Synaptic cell adhesion molecules (CAMs) are a type of membrane surface glycoproteins that mediate the structural and functional interactions between pre- and post-synaptic sites. Synaptic CAMs dynamically regulate synaptic activity and plasticity, and their expression and function are modulated by environmental factors. Synaptic CAMs are also important effector molecules of stress response, and mediate the adverse impact of stress on cognition and emotion. In this review, we will summarize the recent progress on the role of synaptic CAMs in stress, and aim to provide insight into the molecular mechanisms and drug development of stress-related disorders.
Cell Adhesion ; Cell Adhesion Molecules ; physiology ; Humans ; Neuronal Plasticity ; Stress, Physiological ; Stress, Psychological ; Synapses

The slow progress in clinical applications of stem cells and the bewildering mechanisms involved have puzzled many researchers. Recently, the increasing evidences have indicated that cells have superior plasticity in vivo or in vitro, spontaneously or under extrinsic specific inducers. The concept of stem cells may be challenged, or even replaced by the concept of cell plasticity when cell reprogramming technology is progressing rapidly. The characteristics of stem cells are manifestations of cellular plasticity. Incorrect understanding of the concept of stem cells hinders the clinical application of so-called stem cells. Understanding cellular plasticity is important for understanding and treating disease. The above issues will be discussed in detail to prove the reconceptualization of stem cells from cellular plasticity.
Cell Plasticity ; Cellular Reprogramming ; In Vitro Techniques ; Plastics ; Stem Cells

Spinal cord injury (SCI), which is much in the public eye, is still a refractory disease compromising the well-being of both patients and society. In spite of there being many methods dealing with the lesion, there is still a deficiency in comprehensive strategies covering all facets of this damage. Further, we should also mention the structure called the corticospinal tract (CST) which plays a crucial role in the motor responses of organisms, and it will be the focal point of our attention. In this review, we discuss a variety of strategies targeting different dimensions following SCI and some treatments that are especially efficacious to the CST are emphasized. Over recent decades, researchers have developed many effective tactics involving five approaches: (1) tackle more extensive regions; (2) provide a regenerative microenvironment; (3) provide a glial microenvironment; (4) transplantation; and (5) other auxiliary methods, for instance, rehabilitation training and electrical stimulation. We review the basic knowledge on this disease and correlative treatments. In addition, some well-formulated perspectives and hypotheses have been delineated. We emphasize that such a multifaceted problem needs combinatorial approaches, and we analyze some discrepancies in past studies. Finally, for the future, we present numerous brand-new latent tactics which have great promise for curbing SCI.
Animals ; Astrocytes/cytology* ; Axons/physiology* ; Cell Transplantation ; Disease Models, Animal ; Electric Stimulation ; Humans ; Microglia/cytology* ; Motor Neurons/cytology* ; Nerve Regeneration ; Neuroglia/cytology* ; Neuronal Plasticity ; Neurons/cytology* ; Oligodendroglia/cytology* ; Pyramidal Tracts/pathology* ; Recovery of Function ; Regenerative Medicine/methods* ; Spinal Cord Injuries/therapy*

PURPOSE: To evaluate the expression of glial cell line-derived neurotrophic factor (GDNF) and its receptor, GDNF family receptor alpha subunit 1 (GFRα-1) in the pelvic (middle third) vagina and, particularly, in the paravaginal ganglia of nulliparous and primiparous rabbits. METHODS: Chinchilla-breed female rabbits were used. Primiparas were killed on postpartum day 3 and nulliparas upon reaching a similar age. The vaginal tracts were processed for histological analyses or frozen for Western blot assays. We measured the ganglionic area, the Abercrombie-corrected number of paravaginal neurons, the cross-sectional area of the neuronal somata, and the number of satellite glial cells (SGCs) per neuron. The relative expression of both GDNF and GFRα-1 were assessed by Western blotting, and the immunostaining was semiquantitated. Unpaired two-tailed Student t -test or Wilcoxon test was used to identify statistically significant differences (P≤0.05) between the groups. RESULTS: Our findings demonstrated that the ganglionic area, neuronal soma size, Abercrombie-corrected number of neurons, and number of SGCs per neuron were similar in nulliparas and primiparas. The relative expression of both GDNF and GFRα-1 was similar. Immunostaining for both GDNF and GFRα-1 was observed in several vaginal layers, and no differences were detected regarding GDNF and GFRα-1 immunostaining between the 2 groups. In the paravaginal ganglia, the expression of GDNF was increased in neurons, while that of GFRα-1 was augmented in the SGCs of primiparous rabbits. CONCLUSIONS: The present findings suggest an ongoing regenerative process related to the recovery of neuronal soma size in the paravaginal ganglia, in which GDNF and GFRα-1 could be involved in cross-talk between neurons and SGCs.
Blotting, Western ; Carisoprodol ; Female ; Ganglia ; Ganglion Cysts ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Nerve Growth Factors ; Neuroglia ; Neuronal Plasticity ; Neurons ; Postpartum Period ; Rabbits ; Reproduction ; Vagina

Astrocytes are the most abundant cell type in the brain and they make close contacts with neurons and blood vessels. They respond dynamically to various environmental stimuli and change their morphological and functional properties. Both physiological and pathological stimuli can induce versatile changes in astrocytes, as this phenomenon is referred to as ‘astrocytic plasticity’. However, the molecular and cellular mechanisms of astrocytic plasticity in response to various stimuli remain elusive, except for the presence of hypertrophy, a conspicuous structural change which is frequently observed in activated or reactive astrocytes. Here, we investigated differential characteristics of astrocytic plasticity in a stimulus-dependent manner. Strikingly, a stab wound brain injury lead to hypertrophy of astrocytes accompanied by increased GABA expression and tonic GABA release in mouse CA1 hippocampus. In contrast, the mice experiencing enriched environment exhibited astrocytic hypertrophy with enhanced proBDNF immunoreactivity but without GABA signal. Based on the results, we define proBDNF-positive/GABA-negative hypertrophic astrocytes as ‘active’ astrocytes and GABA-positive hypertrophic astrocytes as ‘reactive’ astrocytes, respectively. We propose for the first time that astrocytic proBDNF can be a bona fide molecular marker of the active astrocytes, which are distinct from the reactive astrocytes which show hypertrophy but with aberrant GABA.
Animals ; Astrocytes* ; Blood Vessels ; Brain ; Brain Injuries ; Cell Plasticity ; gamma-Aminobutyric Acid* ; Hippocampus* ; Hypertrophy ; Mice ; Neurons ; Plastics ; Wounds and Injuries ; Wounds, Stab

PURPOSE: Maternal lipopolysaccharide (LPS) injection induces neurodevelopmental disorders, such as cerebral palsy. Exercise activates phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway that enhances neurogenesis. Wnt ligands are also implicated in the hippocampal neurogenesis and synaptic plasticity. Glycogen synthase kinase-3β (GSK-3β) is a downstream molecule of Akt, and GSK-3β is known to modulate hippocampal neurogenesis negatively. METHODS: Cerebral palsy was made by maternal LPS-injection. On the 5 weeks after birth, treadmill running was applied to the rat pups of the exercise groups, for 30 minutes, 5 times a week during 6 weeks. RESULTS: Treadmill running alleviated short-term memory impairments of the cerebral palsy rat pups. Hippocampal cell proliferation was increased and hippocampal apoptosis was suppressed by treadmill running in the cerebral palsy rat pups. Hippocampal phosphorylated-PI3K/PI3K ratio, phosphorylated-Akt/Akt ratio, and Wnt expression were enhanced by treadmill running in the cerebral palsy rat pups. In contrast, hippocampal phosphorylated-GSK-3β/GSK-3β ratio and β-catenin expression were suppressed by treadmill running in the cerebral palsy rat pups. CONCLUSIONS: The results of this study showed that short-term memory improvement due to treadmill running in cerebral palsy occurs via activation of the PI3K-Akt-Wnt pathway.
Animals ; Apoptosis ; Cell Proliferation ; Cerebral Palsy* ; Glycogen Synthase ; Ligands ; Memory, Short-Term* ; Neurodevelopmental Disorders ; Neurogenesis ; Neuronal Plasticity ; Parturition ; Phosphatidylinositol 3-Kinase ; Phosphotransferases ; Proto-Oncogene Proteins c-akt ; Rats* ; Running

OBJECTIVE: In bipolar disorder, serum brain-derived neurotrophic factor (BDNF) level decreases leading to dysfunctions of critical neurotrophic, cellular plasticity and neuroprotective processes. The present study was conducted to evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar mania. METHODS: The present study is a prospective, interventional, open label clinical study conducted on 25 patients of bipolar mania and 25 healthy controls. Detailed history, clinical evaluation including Young Mania Rating Scale (YMRS) scoring and serum BDNF were assessed at baseline for all 50 subjects. The bipolar patients were prescribed tablet oxcarbazepine and followed up after 4 weeks for clinical evaluation and re-estimation of serum BDNF and YMRS scoring. RESULTS: The serum BDNF level in bipolar manic patients were compared with healthy controls at baseline and results revealed that there is a significant reduction (p=0.002) in serum BDNF level in bipolar patients. At follow-up after 4 weeks, the mean change in serum BDNF in bipolar group who were on oxcarbazepine monotherapy was found statistically significant (p=0.02) in comparison to healthy controls. In bipolar group, the YMRS score and serum BDNF at baseline have an inverse relation(r=−0.59) whereas change of the YMRS score had a positive correlation (r=0.67) with the change of serum BDNF over 4 weeks. CONCLUSION: In bipolar mania serum BDNF level is low and it is found to be increased with short term monotherapy with oxcarbazepine.
Bipolar Disorder* ; Brain* ; Brain-Derived Neurotrophic Factor* ; Cell Plasticity ; Clinical Study ; Follow-Up Studies ; Humans ; Prospective Studies

OBJECTIVE: Deficient brain-derived neurotrophic factor (BDNF) is one of the important mechanisms underlying the neuroplasticity abnormalities in schizophrenia. Aberration in BDNF signaling pathways directly or circuitously influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA). For the first time, this study attempts to construct and simulate the BDNF-neurotransmitter network in order to assess the effects of BDNF deficiency on glutamate and GABA. METHODS: Using CellDesigner, we modeled BDNF interactions with calcium influx via N-methyl-D-aspartate receptor (NMDAR)-Calmodulin activation; synthesis of GABA via cell cycle regulators protein kinase B, glycogen synthase kinase and β-catenin; transportation of glutamate and GABA. Steady state stability, perturbation time-course simulation and sensitivity analysis were performed in COPASI after assigning the kinetic functions, optimizing the unknown parameters using random search and genetic algorithm. RESULTS: Study observations suggest that increased glutamate in hippocampus, similar to that seen in schizophrenia, could potentially be contributed by indirect pathway originated from BDNF. Deficient BDNF could suppress Glutamate decarboxylase 67-mediated GABA synthesis. Further, deficient BDNF corresponded to impaired transport via vesicular glutamate transporter, thereby further increasing the intracellular glutamate in GABAergic and glutamatergic cells. BDNF also altered calcium dependent neuroplasticity via NMDAR modulation. Sensitivity analysis showed that Calmodulin, cAMP response element-binding protein (CREB) and CREB regulated transcription coactivator-1 played significant role in this network. CONCLUSION: The study presents in silico quantitative model of biochemical network constituting the key signaling molecules implicated in schizophrenia pathogenesis. It provides mechanistic insights into putative contribution of deficient BNDF towards alterations in neurotransmitters and neuroplasticity that are consistent with current understanding of the disorder.
Amino Acid Transport System X-AG ; Brain-Derived Neurotrophic Factor* ; Calcium ; Calmodulin ; Cell Cycle ; Computer Simulation* ; Cyclic AMP Response Element-Binding Protein ; gamma-Aminobutyric Acid* ; Glutamate Decarboxylase ; Glutamic Acid* ; Glycogen Synthase Kinases ; Hippocampus ; N-Methylaspartate ; Neuronal Plasticity ; Neurotransmitter Agents ; Proto-Oncogene Proteins c-akt ; Schizophrenia* ; Signal Transduction ; Transportation

Perineuronal nets (PNNs) are reticular structures resulting from the aggregation of extracellular matrix (ECM) molecules around the cell body and proximal neurite of specific population of neurons in the central nervous system (CNS). Since the first description of PNNs by Camillo Golgi in 1883, the molecular composition, developmental formation and potential functions of these specialized extracellular matrix structures have only been intensively studied over the last few decades. The main components of PNNs are hyaluronan (HA), chondroitin sulfate proteoglycans (CSPGs) of the lectican family, link proteins and tenascin-R. PNNs appear late in neural development, inversely correlating with the level of neural plasticity. PNNs have long been hypothesized to play a role in stabilizing the extracellular milieu, which secures the characteristic features of enveloped neurons and protects them from the influence of malicious agents. Aberrant PNN signaling can lead to CNS dysfunctions like epilepsy, stroke and Alzheimer's disease. On the other hand, PNNs create a barrier which constrains the neural plasticity and counteracts the regeneration after nerve injury. Digestion of PNNs with chondroitinase ABC accelerates functional recovery from the spinal cord injury and restores activity-dependent mechanisms for modifying neuronal connections in the adult animals, indicating that PNN is an important regulator of neural plasticity. Here, we review recent progress in the studies on the formation of PNNs during early development and the identification of CSPG receptor - an essential molecular component of PNN signaling, along with a discussion on their unique regulatory roles in neural plasticity.
Animals ; Central Nervous System ; physiology ; physiopathology ; Chondroitin Sulfate Proteoglycans ; Extracellular Matrix ; physiology ; Humans ; Neuronal Plasticity ; Neurons ; Receptors, Cell Surface ; physiology