The results of this elegant study published in the recent issue of Cell are the first to show that astrocytes play a key role in modulating neuronal activity and working memory.
A major downside of the medical use of marijuana is the drug’s ill effects on working memory, the ability to transiently hold and process information for reasoning, comprehension and learning. Researchers reporting in the March 2 print issue of the Cell Press journal Cell provide new insight into the source of those memory lapses. The answer comes as quite a surprise: Marijuana’s major psychoactive ingredient (THC) impairs memory independently of its direct effects on neurons. The side effects stem instead from the drug’s action on astroglia, passive support cells long believed to play second fiddle to active neurons.
With these experiments in mice, “we have found that the starting point for this phenomenon - the effect of marijuana on working memory - is the astroglial cells,” said Giovanni Marsicano of INSERM in France.
Read more here: How marijuana makes you forget.
Full article here: Cell. Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD. J. Han et al., 2012.
"Research is to see what everybody else has seen, and to think what nobody else has thought."
— Albert Szent-Györgi (1893-1986) U. S. biochemist
Morphological intricacy of neurons and glia in a mouse hippocampal organotypic slice. Credit to Dr. Chris Henstridge.
Nobel laureate Mario Cappecchi was the first to show a neuro-immune connection in psychiatric diseases. In this provocative and very interesting study Williamson and colleagues make a link between immunity and memory. They report that neonatal bacterial infection can have long-lasting negative effects on learning and memory later in adult life. Here is the abstract of the study published in October in the Journal of Neuroscience.
The proinflammatory cytokine interleukin-1β (IL-1β) is critical for normal hippocampus (HP)-dependent cognition, whereas high levels can disrupt memory and are implicated in neurodegeneration. However, the cellular source of IL-1β during learning has not been shown, and little is known about the risk factors leading to cytokine dysregulation within the HP. We have reported that neonatal bacterial infection in rats leads to marked HP-dependent memory deficits in adulthood. However, deficits are only observed if unmasked by a subsequent immune challenge [lipopolysaccharide (LPS)] around the time of learning. These data implicate a long-term change within the immune system that, upon activation with the “second hit,” LPS, acutely impacts the neural processes underlying memory. Indeed, inhibiting brain IL-1β before the LPS challenge prevents memory impairment in neonatally infected (NI) rats. We aimed to determine the cellular source of IL-1β during normal learning and thereby lend insight into the mechanism by which this cytokine is enduringly altered by early-life infection. We show for the first time that CD11b+ enriched cells are the source of IL-1β during normal HP-dependent learning. CD11b+ cells from NI rats are functionally sensitized within the adult HP and produce exaggerated IL-1β ex vivo compared with controls. However, an exaggerated IL-1β response in vivo requires LPS before learning. Moreover, preventing microglial activation during learning prevents memory impairment in NI rats, even following an LPS challenge. Thus, early-life events can significantly modulate normal learning-dependent cytokine activity within the HP, via a specific, enduring impact on brain microglial function.
Read the full study here
Abstract of the study published by Wilhelmsson et al., in PNAS.
Reactive astrocytes in neurotrauma, stroke, or neurodegeneration are thought to undergo cellular hypertrophy, based on their morphological appearance revealed by immunohistochemical detection of glial fibrillary acidic protein, vimentin, or nestin, all of them forming intermediate filaments, a part of the cytoskeleton. Here, we used a recently established dye-filling method to reveal the full three-dimensional shape of astrocytes assessing the morphology of reactive astrocytes in two neurotrauma models. Both in the denervated hippocampal region and the lesioned cerebral cortex, reactive astrocytes increased the thickness of their main cellular processes but did not extend to occupy a greater volume of tissue than nonreactive astrocytes. Despite this hypertrophy of glial fibrillary acidic protein-containing cellular processes, interdigitation between adjacent hippocampal astrocytes remained minimal. This work helps to redefine the century-old concept of hypertrophy of reactive astrocytes.
Full paper here