Publications by authors named "Ako Kato"

Article Synopsis
  • Monoacylglycerol lipase (MAGL) breaks down 2-arachidonoylglycerol (2-AG) in the brain, leading to increased neuroinflammation and reduced prostaglandins when inhibited.
  • MAGL inhibition, either through pharmacological means or genetic deletion, results in heightened microglial reactivity in the cerebellum and impaired motor coordination, but not in the hippocampus.
  • Using a COX-2 inhibitor can mitigate cerebellar function deficits and microglial reactivity without affecting the hippocampus, suggesting region-specific effects of MAGL inhibition in the brain.
View Article and Find Full Text PDF

Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug with only incompletely understood mechanisms of action. Previous work, using models of acute nociceptive pain, indicated that analgesia by acetaminophen involves an indirect activation of CB receptors by the acetaminophen metabolite and endocannabinoid reuptake inhibitor AM 404. However, the contribution of the cannabinoid system to antihyperalgesia against inflammatory pain, the main indication of acetaminophen, and the precise site of the relevant CB receptors have remained elusive.

View Article and Find Full Text PDF

Neuroplastic changes at the spinal synapses between primary nociceptors and second order dorsal horn neurons play key roles in pain and analgesia. NMDA receptor-dependent forms of long-term plasticity have been studied extensively at these synapses, but little is known about possible contributions of the endocannabinoid system. Here, we addressed the role of cannabinoid (CB)1 receptors in activity-dependent plasticity at these synapses.

View Article and Find Full Text PDF

A new class of N-acetyl-D-glucosamine (GlcNAc) mimics for E-selectin antagonists was designed and synthesized. The mimic consists of a cyclohexane ring substituted with alkyl substituents adjacent to the linking position of the fucose moiety. Incorporation into E-selectin antagonists led to the test compounds 8 and the 2'-benzoylated analogues 21, which exhibit affinities in the low micromolar range.

View Article and Find Full Text PDF

Diminished synaptic inhibition in the spinal dorsal horn is a major contributor to chronic pain. Pathways that reduce synaptic inhibition in inflammatory and neuropathic pain states have been identified, but central hyperalgesia and diminished dorsal horn synaptic inhibition also occur in the absence of inflammation or neuropathy, solely triggered by intense nociceptive (C-fiber) input to the spinal dorsal horn. We found that endocannabinoids, produced upon strong nociceptive stimulation, activated type 1 cannabinoid (CB1) receptors on inhibitory dorsal horn neurons to reduce the synaptic release of gamma-aminobutyric acid and glycine and thus rendered nociceptive neurons excitable by nonpainful stimuli.

View Article and Find Full Text PDF