Neuroscience
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Cannabinoids (CBs) have recently been approved to exert broad anti-inflammatory activities in experimental models of multiple sclerosis (MS). It has been demonstrated that these compounds could also have effects on neurodegeneration, demyelination, and autoimmune processes occurring in the pathology of MS. However, the clinical use of CBs is limited by their psychoactive effects. ⋯ This effect of CBD and PEA was accompanied by diminished inflammation, demyelination, axonal damage and inflammatory cytokine expression while concurrent administration of CBD (5mg/kg) and PEA (5mg/kg) was not as effective as treatment with either drug per se. These results suggest that, CBD and PEA, non-psychoactive CBs, attenuate neurobehavioral deficits, histological damage, and inflammatory cytokine expression in MOG-immunized animals. However, there is an antagonistic interaction between CBD and PEA in protection against MOG-induced disease.
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Interleukin-23 (IL-23) is required for T helper 17 (Th17) cell responses and IL-17 production in ischemic stroke. We previously showed that the IL-23/IL-17 axis aggravates immune injury after cerebral infarction in mice. However, IL-23 might activate other cytokines and transcription factor forkhead box P3 (Foxp3) production in cerebral ischemia. We aimed to determine whether IL-23p19 knockdown prevents cerebral ischemic injury by reducing ischemic-induced inflammation. ⋯ IL-23p19 knockdown prevents delayed cerebral ischemic injury by dampening the ischemia-induced inflammation, and is a promising approach for clinically managing ischemic stroke.
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This study aimed to clarify whether ischemia-induced early growth response 1 (EGR1) influenced the outcomes of experimental stroke by regulating brain-derived neurotrophic factor (BDNF) expression. ⋯ Ischemia-induced EGR1 expression may exaggerate brain injury by reducing BDNF expression. Inhibiting EGR1 may become a potential treatment for improving outcomes of ischemic stroke.
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Human African trypanosomiasis or sleeping sickness is a severe, neglected tropical disease caused by the extracellular parasite Trypanosoma brucei. The disease, which leads to chronic neuroinflammation, is characterized by sleep and wake disturbances, documented also in rodent models. In rats and mice infected with Trypanosoma brucei brucei, we here tested the hypothesis that the disease could target neurons of the lateral hypothalamus (LH) containing orexin (OX)-A or melanin-concentrating hormone (MCH), implicated in sleep/wake regulation. ⋯ Interestingly, in infected mice the diurnal spontaneous Fos oscillation was reversed, with a proportion of OX-A/Fos neurons significantly higher at daytime than at nighttime. Altogether the findings reveal a progressive decrease of OX-A and MCH neurons and dysregulation of OX-A neuron diurnal activity in rodent models of sleeping sickness. The data point to the involvement of these peptidergic neurons in the pathogenesis of sleep/wake alterations in the disease and to their vulnerability to inflammatory signaling.
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Cyclic AMP signaling is critical for activity-dependent refinement of neuronal circuits. Global disruption of adenylyl cyclase 1 (AC1), the major calcium/calmodulin-stimulated adenylyl cyclase in the brain, impairs formation of whisker-related discrete neural modules (the barrels) in cortical layer 4 in mice. Since AC1 is expressed both in the thalamus and the neocortex, the question of whether pre- or postsynaptic (or both) AC1 plays a role in barrel formation has emerged. ⋯ In the third line, all calcium-stimulated adenylyl cyclases (both AC1 and AC8) are deleted in cortical excitatory neurons. These mice have normal barrels. Taken together, these results indicate that thalamic AC1 plays a major role in patterning and refinement of the mouse TC circuitry.