CB1 Receptor Knockouts Have An Accelerated Cognitive Decline


Study finds that CB1 receptor knockout mice have increased brain inflammation, which leads to earlier cognitive decline.

Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1?/?), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus. The age-dependent decrease in neuronal numbers in Cnr1?/? mice was not related to decreased neurogenesis or to epileptic seizures. However, enhanced neuroinflammation characterized by an increased density of astrocytes and activated microglia as well as an enhanced expression of the inflammatory cytokine IL-6 during aging was present in the hippocampus of Cnr1?/? mice. The ongoing process of pyramidal cell degeneration and neuroinflammation can exacerbate each other and both contribute to the cognitive deficits. Deletion of CB1 receptors from the forebrain GABAergic, but not from the glutamatergic neurons, led to a similar neuronal loss and increased neuroinflammation in the hippocampus as observed in animals lacking CB1 receptors in all cells. Our results suggest that CB1 receptor activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation. (via.)


Heightened immune response in socially anxious


Everyone experiences social stress, whether it is nervousness over a job interview, difficulty meeting people at parties, or angst over giving a speech. In a new report, UCLA researchers have discovered that how your brain responds to social stressors can influence the body’s immune system in ways that may negatively affect health.

Lead author George Slavich, a postdoctoral fellow at the UCLA Cousins Center for Psychoneuroimmunology, and senior author Shelley Taylor, a UCLA professor of psychology, show that individuals who exhibit greater neural sensitivity to social rejection also exhibit greater increases in inflammatory activity to social stress. [...]

The researchers recruited 124 individuals — 54 men and 70 women — and put them into two awkward social situations. First, in the lab, the volunteers completed the Trier Social Stress Test (TSST), which involves preparing and delivering an impromptu speech and performing difficult mental arithmetic, both in front of a socially rejecting panel of raters wearing white lab coats. Mouth swabs were taken before and after the public-speaking tasks to test for changes in two key biomarkers of inflammatory activity — a receptor for tumor necrosis factor-? (sTNF?RII) and interleukin-6 (IL-6).

In a second session, 31 of the participants received an MRI brain scan while playing a computerized game of catch with what they believed were two other real people. The researchers focused on two areas of the brain known to respond to social stress — the dorsal anterior cingulate cortex (dACC) and the anterior insula.

At first, the game was between all three “players.” Halfway through the game, however, the research subject was excluded, leading to an experience of social rejection. The researchers then examined how differences in neural activity during social rejection correlated with differences in inflammatory responses to the TSST.

Their results showed that individuals who exhibited greater neural activity in the dorsal anterior cingulate cortex and anterior insula during social rejection in the brain scanner also exhibited greater increases in inflammatory activity when exposed to acute social stress in the lab.

“This is further evidence of how closely our mind and body are connected,” Slavich said. “We have known for a long time that social stress can ‘get under the skin’ to increase risk for disease, but it’s been unclear exactly how these effects occur. To our knowledge, this study is the first to identify the neurocognitive pathways that might be involved in inflammatory responses to acute social stress.” [...]

One critical question raised by the present findings is why neural sensitivity to social rejection would cause an increase in inflammation. There are several possible reasons, the authors note. For one, since physical threats have historically gone hand in hand with social threat or rejection, inflammation may be triggered in anticipation of a physical injury. Inflammatory cytokines — proteins that regulate the immune system — are released in response to impending (or actual) physical assault because they accelerate wound-healing and reduce the risk of infection.

via.

This may also be of interest: Tylenol (acetaminophen) eases social anxiety.