Neuroscience
-
Comparative Study
HAMI 3379, a CysLT2R antagonist, dose- and time-dependently attenuates brain injury and inhibits microglial inflammation after focal cerebral ischemia in rats.
Cysteinyl leukotrienes (CysLTs) induce inflammatory responses by activating their receptors, CysLT1R and CysLT2R. We have reported that CysLT2R is involved in neuronal injury, astrocytosis, and microgliosis, and that intracerebroventricular (i.c.v.) injection of the selective CysLT2R antagonist HAMI 3379 protects against acute brain injury after focal cerebral ischemia in rats. In the present study, we clarified features of the protective effect of intraperitoneally-injected HAMI 3379 in rats. ⋯ In comparison, the CysLT1R antagonist pranlukast did not affect microglial activation and IFN-γ release, but inhibited astrocyte proliferation and reduced serum IL-4. Thus, we conclude that HAMI 3379 has a protective effect on acute and subacute ischemic brain injury, and attenuates microglia-related inflammation. CysLT2R antagonist(s) alone or in combination with CysLT1R antagonists may be a novel class of therapeutic agents in the treatment of ischemic stroke.
-
Neurobiological and genetic mechanisms underlying increased intake of and preference for nutritive sugars over non-nutritive sweeteners are not fully understood. We examined the roles of subnuclei of the amygdala in the shift in preference for a nutritive sugar. Food-deprived mice alternately received caloric sucrose (1.0 M) on odd-numbered training days and a non-caloric artificial sweetener (2.5 mM saccharin) on even-numbered training days. ⋯ Microlesions with iontophoretic excitotoxin injections into the CeA did not block the training-dependent changes. These results suggest that food-deprived animals selectively shift their preference for a caloric sugar over a non-caloric sweetener through the alternate consumption of caloric and non-caloric sweet substances. The present data also suggest that the BLA, but not CeA, plays a role in the selective shift in sweetener preference.
-
Injury potential, which refers to a direct current voltage between intact and injured nerve ends, is mainly caused by injury-induced Ca2+ influx. Our previous studies revealed that injury potential increased with the onset and severity of spinal cord injury (SCI), and an application of applied electric field stimulation (EFS) with the cathode distal to the lesion could delay and attenuate injury potential formation. As Ca2+ influx is also considered as a major trigger for secondary injury after SCI, we hypothesize that EFS would protect an injured spinal cord from secondary injury and consequently improve functional and pathological outcomes. ⋯ Results suggest that early EFS could significantly reduce spinal cord degeneration and improve functional and historical recovery. Furthermore, these neuroprotective effects may be related to the inhibition of secondary apoptotic responses after SCI. These findings support further investigation of the future clinical application of EFS after SCI.
-
Repeated stress can elicit symptoms of depression and anxiety. The amygdala is a significant contributor to the expression of emotion and the basolateral amygdala (BLA) is a major target for the effects of stress on emotion. The adolescent time period may be particularly susceptible to the effects of stress on emotion. ⋯ The magnitude and dendritic location of these differences varied between the BA and LAT nuclei in strong contrast to the stress-induced increases in spine number seen in adults. These results demonstrate that repeated stress during adolescence has markedly different effects on BLA neuronal morphology, and the extent of these changes is BLA nucleus-dependent. Moreover, altered neuroanatomy was associated with age-dependent effects of repeated stress on generalization of fear, and may point to the necessity for different approaches to target stress-induced changes in adolescents.
-
Comparative Study
NAMPT inhibitor and metabolite protect mouse brain from cryoinjury through distinct mechanisms.
Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme in the biosynthesis of nicotinamide adenine dinucleotide (NAD). In the brain, NAMPT is primarily expressed in neurons and can prevent neuronal degeneration. NAMPT is also highly expressed in inflammatory cells, and is responsible for their activation. ⋯ In addition, FK866 significantly attenuated the activation of astrocytes and Iba1-positive macrophages/microglia, and decreased the NAD, while NMN had no such effects. Taken together, both FK866 and NMN attenuate traumatic brain injury. However, FK866 acts via the inhibition of the NAMPT activity in inflammatory cells resulting in the inhibition of inflammation, whereas NMN is effective via replenishing NAD.