Abstract
We have previously demonstrated that antagonism of glutamate NMDA receptors or activation of endocannabinoid receptors could reduce experimentally induced neuroinflammation within the hippocampus of young rats. In the current study, we investigated whether pharmacological manipulation of glutamate or endocannabinoid neurotransmission could reduce naturally-occurring neuroinflammation within the hippocampus of aged rats. We investigated whether UCM707, an inhibitor of endocannabinoid re-uptake, WIN- 55,212-2, an endocannabinoid receptor agonist, and URB597, an inhibitor of endocannabinoid catabolism, or memantine, a non-competitive, low-affinity, inhibitor of the open NMDA receptor channel, could reduce the number of MHC II-IR microglia within the hippocampus. All of the drugs, except URB597, reduced the number of reactive microglia, as compared to vehicle treated rats. The current results suggest potential pharmacological approaches that may mitigate the pathological consequences of chronic brain inflammation associated with numerous neurodegenerative diseases.
Highlights
Neuroinflammation contributes to the pathogenesis of numerous age-related neurodegenerative disorders [1,2,3]
The current studied determined whether pharmacological manipulation of glutamate or endocannabinoid neurotransmission within the aged rat brain could reduce a critical indicator of neuroinflammation, the number of activated microglia
The current study demonstrated that pharmacological manipulation of glutamate or cannabinoid neurotransmission can significantly reduce the number of MHC II-IR microglia within the aged hippocampus
Summary
Neuroinflammation contributes to the pathogenesis of numerous age-related neurodegenerative disorders [1,2,3]. Naturally occurring neuroinflammation does not respond to anti-inflammatory drugs [4] which may explain the numerous failures of interventional studies using anti-inflammatory therapies in patients with Alzheimer’s disease [5]. We investigated some alternative approaches using drugs that we have previously shown could effectively reduce the pathological, neurochemical, molecular, genetic and behavioral expressions of experimentally-induced neuroinflammation in the young rat brain [6,7,8,9,10,11,12]. The current studied determined whether pharmacological manipulation of glutamate or endocannabinoid neurotransmission within the aged rat brain could reduce a critical indicator of neuroinflammation, the number of activated microglia. We have previously demonstrated that memantine can reduce the cognitive and pathological consequences of chronic neuroinflammation in young rats exposed to lipopolysaccharide [10,12]
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