Neurochemistry international
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Several lines of evidence from both animal and clinical studies have demonstrated that dorsal column (DC) pathway plays a critical role in visceral pain transmission from the spinal cord to supraspinal center. The descending pain modulation pathway from the rostral ventromedial medulla (RVM) area has been implicated in visceral nociceptive neurotransmission. Previous studies have demonstrated that the multiple protein kinase signaling transduction cascades in the RVM area contribute to the descending facilitation of inflammatory pain and neuropathic pain. ⋯ Our results showed that acetic acid-induced visceral nociception produced a persistent activation of ERK in the RVM area and a microinjection of a mitogen-activated ERK kinase (MEK) inhibitor, U0126, into the RVM area significantly inhibited the visceral noxious stimulation-induced behaviors in rats. A microinjection of lidocaine into the nucleus gracilis (NG) also inhibited the activation of ERK in the RVM area. The current study indicates that activated ERK signaling pathway in the RVM area is dependent on afferent input from dorsal column pathway and may contribute to acetic acid-induced visceral nociception.
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An increasing amount of evidence has emerged to suggest that neuroinflammatory process is involved in the pathogenesis of Parkinson's disease (PD). Activated microglia and astrocytes are found in the substantia nigra (SN) of Parkinson's disease brains as well as in animal models of Parkinson's disease. Although reactive astrocytes are involved in the progression of PD, the role of reactive astrocytes in neuroinflammation of PD has received limited attention to date. ⋯ Besides, GSK-3β inhibitor LiCl and SB415286 inhibited the GSK-3β/NF-κB signaling pathway, leading to the reduction of proinflammatory molecules in 6-OHDA-activated astrocytes. These results confirmed that GSK-3β inhibitor LiCl and SB415286 provide protection against neuroinflammation in 6-OHDA-treated astrocytes. Therefore, GSK-3β may be a potential therapeutic target for the treatment of PD.
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Traumatic brain injury (TBI) is a devastating disease that commonly causes persistent mental disturbances and cognitive deficits. Although studies have indicated that overproduction of free radicals, especially superoxide (O2(-)) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a common underlying mechanism of pathophysiology of TBI, little information is available regarding the role of apocynin, an NADPH oxidase inhibitor, in neurological consequences of TBI. Therefore, the present study evaluated the therapeutic potential of apocynin for treatment of inflammatory and oxidative damage, in addition to determining its action on neuromotor and memory impairments caused by moderate fluid percussion injury in mice (mLFPI). ⋯ Moreover, apocynin treatment reduced oxidative damage (protein carbonyl, lipoperoxidation) and was effective against mLFPI-induced Na(+), K(+)-ATPase activity inhibition. The present results were accompanied by effective reduction in lesion volume when analyzed 7days after neuronal injury. These data suggest that superoxide (O2(-)) derived from NADPH oxidase can contribute significantly to cognitive impairment, and that the post injury treatment with specific NADPH oxidase inhibitors, such as apocynin, may provide a new therapeutic approach to the control of neurological disabilities induced by TBI.
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Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. ⋯ In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any effect of etazolate and fluoxetine on CORT and BDNF levels in normal control mice. In conclusion, the results of the present study suggested compelling evidences that etazolate has more marked effect on depression-like behavior in mice, which is atleast in part may be related to their modulating effects on the HPA axis and BDNF level.
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Exposure of an organism to stress, results in oxidative stress and increased nitric oxide (NO) production in the brain. The role of the processes caused by chronic stress in the prefrontal cortex has not been fully investigated. Considering that chronic stress increases NO production by the enzyme nitric oxide synthase (NOS), we examined the cytosolic neuronal (nNOS) or inducible (iNOS) protein levels in the prefrontal cortex of rats exposed to 21d of chronic social isolation stress, an animal model of depression, alone or in combination with 2h of acute immobilization or cold (4°C) stress (combined stress). ⋯ Downregulated redox GSH status as well as decreased activity of CuZnSOD and MnSOD suggests the existence of oxidative stress which remained as such following combined stressors. Changes in redox-status associated with decreased Hsp70i protein expression enabled NF-κB translocation into the nucleus, causing increased cytosolic nNOS and iNOS protein expression. Results suggest that NOS signaling pathway plays a differential role between acute and chronic stress whereby state of oxidative/nitrosative stress after chronic social isolation is caused, at least in part, by NF-κB activation and increased iNOS protein expression.