Using behavioral, pharmacological, and molecular methods, lots of studies reveal that depression is closely related to the abnormal neural plasticity processes occurring in the prefrontal cortex and limbic system such as the hippocampus and amygdala. Meanwhile, functions of the brain-derived neurotrophic factor (BDNF) and the other neurotrophins in the pathogenesis of depression are well known. The maladaptive neuroplastic in depression may be related to alterations in the levels of neurotrophic factors, which play a central role in plasticity. Enhancement of neurotrophic factors signaling has great potential in therapy for depression. This review highlights the relevance of neurotrophic factors mediated neural plasticity and pathophysiology of depression. These studies reviewed here may suggest new possible targets for antidepressant drugs such as neurotrophins, their receptors, and relevant signaling pathways, and agents facilitating the activation of gene expression and increasing the transcription of neurotrophic factors in the brain.

BackgroundAlthough some trials assessed the effectiveness of aerobic exercise for Parkinson's disease (PD), the role of aerobic exercise in the management of PD remained controversial.ObjectiveThe purpose of this systematic review is to evaluate the evidence about whether aerobic exercise is effective for PD.MethodsSeven electronic databases, up to December 2013, were searched to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality based on PEDro scale. Standardised mean difference (SMD) and 95% confidence intervals (CI) of random-effects model were calculated. And heterogeneity was assessed based on the I2 statistic.Results18 randomized controlled trials (RCTs) with 901 patients were eligible. The aggregated results suggested that aerobic exercise should show superior effects in improving motor actions (SMD, −0.57; 95% CI −0.94 to −0.19; p = 0.003), balance (SMD, 2.02; 95% CI 0.45 to 3.59; p = 0.01), and gait (SMD, 0.33; 95% CI 0.17 to 0.49; p<0.0001) in patients with PD, but not in quality of life (SMD, 0.11; 95% CI −0.23 to 0.46; p = 0.52). And there was no valid evidence on follow-up effects of aerobic exercise for PD.ConclusionAerobic exercise showed immediate beneficial effects in improving motor action, balance, and gait in patients with PD. However, given no evidence on follow-up effects, large-scale RCTs with long follow-up are warrant to confirm the current findings.

Transient receptor potential vanilloid type-1 (TRPV1) is a ligand-gated nonselective cation channel that has been well characterized in peripheral pain pathway. Recent evidence from animal models of temporal lobe epilepsy (TLE) has supported the important role of TRPV1 in epileptogenesis. In this study, we investigated the expression and cellular distribution of TRPV1 in the temporal cortex (CTX) and hippocampus (HPC) from 26 patients with mesial TLE (MTLE) compared with 12 histologically normal samples. Reverse transcription-PCR and Western blotting revealed up-regulated mRNA and protein levels of TRPV1 in the MTLE group versus the control group. Immunohistochemistry data demonstrated that TRPV1 was mainly distributed in the cell bodies and dendrites of neurons. Double-labeled immunofluorescence further revealed that TRPV1 was localized on NeuN-positive neurons and GFAP-positive astrocytes, but not on HLA-positive microglia. In addition, its co-localization with glutamate and gamma-aminobutyric acid (GABA) indicated that TRPV1 was distributed on both glutamatergic and GABAergic neurons. Moreover, nerve growth factor, a sensitizing factor for TRPV1, was showed a higher expression pattern in MTLE patients. Taken together, our findings suggest that the overexpression and distribution patterns of TRPV1 might be involved in the pathogenesis and epileptogenesis of human MTLE.

Increasing evidence indicates that there exists a reciprocal communication between the immune system and the brain. Interleukin 1beta (IL-1beta), a proinflammatory cytokine produced during immune challenge, is believed to be one of the mediators of immune-to-brain communication, but how it gets into the brain is unknown because of its large molecular weight and difficulty in crossing the blood-brain barrier. Our previous work has demonstrated that IL-1 receptor type I is strongly expressed in the glomus cells of rat carotid body (CB), a well characterized polymodal chemoreceptive organ which serves not only for the detection of hypoxia, hypercapnia and acidity, but also for low temperature and blood glucose. The present study was designed to test whether IL-1beta could stimulate the CB glomus cells and alter the discharge properties in the carotid sinus nerve, the afferent nerve innervating the organ. The results from whole-cell patch-clamp recordings and calcium imaging showed that extracellular application of IL-1beta significantly decreased the outward potassium current and triggered a transient rise in [Ca(2+)](i) in the cultured glomus cells of rat CB. Furthermore, by using extracellular recordings and pharmacological intervention, it was found that IL-1beta stimulation of the CB in the anaesthetized rat in vivo significantly increased the discharge rate in the carotid sinus nerve, most probably mediated by ATP release. This experiment provides evidence that the CB responds to cytokine stimulation and proposes the possibility that the CB might play a role in immune-to-brain communication.

Experimental studies have demonstrated significant secondary damage (including cell apoptosis, blood-brain barrier disruption, inflammatory responses, excitotoxic damage, and free radical production) after traumatic brain injury (TBI). Quercetin is a natural flavonoid found in high quantities in fruits and vegetables, and may be a potential antioxidant and free radical scavenger. The purpose of this study was to determine the effects of quercetin on TBI-induced upregulation of oxidative stress, inflammation, and apoptosis in adult Sprague-Dawley rats. Animals were subjected to Feeney's weight-drop injury, thus inducing the parietal contusion brain injury model. Quercetin was administered (30 mg/kg intraperitoneal injection) 0, 24, 48, and 72 h after TBI. Quercetin reduced cognitive deficits, the number of TUNEL- and ED-1-positive cells, the protein expressions of Bax and cleaved-caspase-3 proteins, and the levels of TBARS and proinflammatory cytokines, and increased the activity of antioxidant enzymes (GSH-Px, SOD, and CAT) at 1 week after TBI. Our results suggest that in TBI rats, quercetin improves cognitive function owing to its neuroprotective action via the inhibition of oxidative stress, leading to a reduced inflammatory response, thereby reducing neuronal death.

Focal cortical dysplasias (FCDs) are increasingly recognized as important causes of medically intractable epilepsy. To understand the potential role of the interleukin 17 (IL-17) system in the epileptogenesis of FCDs, we studied the expression patterns of the IL-17 system in 15 FCD type Ia (FCDIa), 12 FCD type IIa (FCDIIa), and 12 FCD type IIb (FCDIIb) cortical lesions and compared the results with those in cerebral cortex from 10 control patients. Protein levels of IL-17, IL-17 receptor (IL-17R), and downstream factors of the IL-17 pathway (nuclear factor-κB activator 1 [NFκB; ACT1] and NFκB-p65) were markedly elevated in FCDIa, FCDIIa, and FCDIIb. Moreover, protein levels of IL-17 and IL-17R positively correlated with the frequency of seizures in FCD patients. Immunostaining indicated that IL-17 and IL-17R are highly expressed in neuronal microcolumns, dysmorphic neurons, balloon cells, astrocytes, and vascular endothelial cells. Nuclear factor-κB activator 1 and NFκB-p65 were diffusely expressed in FCDs. In addition, we detected a few IL-17-positive, CD4-positive T lymphocytes in FCDIIa and FCDIIb but not in FCDIa. Taken together, these findings suggest that the overexpression of the IL-17 system and the activation of the IL-17 signal transduction pathway may be involved in the epileptogenicity of cortical lesions in FCDs, thus representing a novel potential target for antiepileptic therapy.

Tuberous sclerosis complex (TSC) and focal cortical dysplasia type IIb (FCDIIb) are characterized by epilepsy-associated cerebral cortical malformations. To understand the potential role of the inflammatory cytokine interleukin 6 (IL-6) in the pathogenesis of these lesions, we analyzed the IL-6 system in TSC and FCDIIb cortical lesions and in control cortex (CTX). Greater messenger RNA and protein levels of IL-6 and of its receptors (i.e. IL-6 receptor [IL-6R] and glycoprotein 130 [gp130]) were observed in TSC and FCDIIb lesions versus CTX. Immunohistochemical analyses indicated that IL-6 and IL-6R were strongly expressed in misshapen cells, namely, dysmorphic neurons, giant neurons, and balloon cells. Glycoprotein 130 was diffusely expressed in nearly all cell types. Most IL-6/IL-6R+ misshapen cells colabeled with neuronal rather than astrocytic markers, suggesting a neuronal lineage; most IL-6/IL-6R+ balloon cells in FCDIIb expressed glial fibrillary acidic protein. Protein levels of Janus kinase 2 and phosphorylated signal transducer and activator of transcription 3 were greater than in CTX, suggesting involvement of the gp130-Janus kinase 2-signal transducer and activator of transcription 3 pathway in IL-6 signal transduction. Soluble IL-6R, but not soluble gp130, was greater in TSC and FCDIIb lesions than in CTX, indicating activation of this trans-signaling pathway. These results suggest that overexpression in the IL-6 system and activation of IL-6 signal transduction pathways may contribute to the pathogenesis of cortical lesions in TSC and FCDIIb.

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