In the article “Cannabis and the Developing Brain: Insights into Its Long-Lasting Effects” by Yasmin L. Hurd, Olivier J. Manzoni, Mikhail V. Pletnikov, Francis S. Lee, Sagnik Bhattacharyya, and Miriam Melis, which appeared on pages [8250–8258][1] of the October 16, 2019 issue, one of the

While effective in treating abdominal pain, opioids have significant side effects. Recent legalization of cannabis will likely promote use of cannabinoids as an adjunct or alternative to opioids, despite a lack of evidence. We aimed to investigate whether cannabinoids inhibit mouse colonic nociception, alone or in combination with opioids at low doses. Experiments were performed on C57BL/6 male and female mice. Visceral nociception was evaluated by measuring visceromotor responses (VMR), afferent nerve mechanosensitivity in flat-sheet colon preparations, and excitability of isolated DRG neurons. Blood oxygen saturation, locomotion, and defecation were measured to evaluate side effects. An agonist of cannabinoid 1 receptor (CB1R), arachidonyl-2′-chloroethylamide (ACEA), dose-dependently decreased VMR. ACEA and HU-210 (another CB1R agonist) also attenuated colonic afferent nerve mechanosensitivity. Additionally, HU-210 concentration-dependently decreased DRG neuron excitability, which was reversed by the CB1...

The mature neocortex consists of 6 layers, which develop radially in an inside-out fashion wherein the deeper layers, closest to the proliferative regions, develop first, followed by the superficial layers ([Angevine and Sidman, 1961][1]). Differentiating neurons and progenitors express

Widespread legalization of recreational cannabis has resulted in an increase of past-month cannabis use among pregnant women, yet the long-term effects of prenatal cannabis exposure on cognitive flexibility and its underlying neural substrates remains l...

Cisplatin is a commonly used chemotherapy that has a dose limiting effect whereby 30-70% of patients develop peripheral neuropathy. Cisplatin induced neuropathy (CIN) presents in a stocking and glove pattern with patients reporting symptoms of allodynia...

The impact of various post-translational modifications (PTMs) on tau protein aggregation has been well documented. However, whether these PTMs such as phosphorylation or glycosylation are drivers of aggregation or mere functional modulators is still an ...

Cholesterol homeostasis is maintained by balancing synthesis, uptake, and catabolism, with excess cholesterol being acytylated (prior to storage) or oxidized (prior to excretion as bile acid). A growing body of literature suggests that brain cholesterol...

The cannabinoid system in the hippocampus is thought to mediate impairment of learning and memory in marijuana users. To test the hypothesis that adolescents are more sensitive than adults to the acute effects of marijuana on hippocampal cannabinoid function, we examined the effects of the cannabinoid agonist WIN55,212-2 on GABA-A receptor mediated inhibitory neurotransmission in the CA1 hippocampal area. Hippocampal slices were prepared from adolescent (ages 28-33 days) or adult (ages 100-150 days) rats. GABA-A receptor-mediated synaptic currents were pharmacologically isolated and recorded using a whole-cell patch clamp configuration. The GABA-A receptor-mediated currents in slices from adolescent rats showed a significant 35% decrease in the presence of WIN55,212-2 (1 uM) (n=6, p <0.01). However, there was no significant effect of WIN55,212-2 on synaptic responses of neurons from adult rats (n=4, p=0.1). The difference between the two groups was significant (p=0.03, independent t-test). This result sugg...

Action Potential Shaping by Stimulus History Gonzalo G. de Polavieja, Annette Harsch, Ingo Kleppe, Hugh P. C. Robinson, and Mikko Juusola (see pages [5657-5665][1]) In usual parlance, “action potential” is synonymous with all-or-none, with each event a uniform shape. In this view, the large

Alzheimer’s disease (AD) and other dementias are the leading cause of disability in older individuals, the prevalence of which has more than doubled in the last thirty years. Although recent AD clinical trials suggest that early or presymptomatic treatm...