Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology

Olmos-Alonso, Schetters, et al. recently conducted a study to research potential ways to prevent patients from developing Alzheimer’s Disease (AD). Specifically they wanted to see the effect that activation of the colony-stimulating factor 1 receptor (CSF1R) had on progression of the disease, since the CSF1R promotes the creation and activation of microglial cells, which can lead to many neurodegenerative disorders, such as AD. The study provided some early evidence that inhibition of CSF1R could be a potential treatment to prevent the progression of AD.

Although this study only used mice, I think it was interesting to see that they had potentially found a pathway to interrupt in order to prevent, or at least slow, the progression of Alzheimer’s. As some one who has Alzheimer’s in his family history, it at least eases my fears when I see that steps are being made towards treatments for the disorder. I do realize that a lot more work and research needs to be done into this pathway and how exactly a medication could treat it, but I still found this article to be noteworthy. What do you think?

Link to the article

Olmos-Alonso, Adrian, Sjoerd T. T. Schetters, Sarmi Sri, Katharine Askew, Renzo Mancuso, Mariana Vargas-Caballero, Christian Holscher, V. Hugh Perry, and Diego Gomez-Nicola. “Pharmacological Targeting of CSF1R Inhibits Microglial Proliferation and Prevents the Progression of Alzheimer’s-like Pathology.” Brain 139.3 (2016): 891-907. Web.

Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical serotonin/glutamate neurotransmission

In a novel study by Linge and colleagues, cannabidiol (CBD) was shown to exhibit strong anxiolytic and antidepressant effects in mice. The study also elucidated CBD’s mechanism of action on serotonin receptors in the brain. Their findings indicate that CBD could represent a novel fast-acting antidepressant drug.

CBD is the main non-psychotomimetic component of marijuana. This means that behind THC, the compound responsible for many of the mind-altering affects we collectively refer to as a “high,” CBD produces the majority of it’s therapeutic benefit without inducing highness. Utilizing the olfactory bulbectomy (OBX) mouse model of depression, researchers studied the behavioral efficacy of CBD via the enhancement of serotonergic and glutamatergic transmission through the modulation of 5-HT 1A receptors. Classical antidepressants act through similar serotonergic attenuation whereas the effects of fast-acting antidepressants seem to be mediated mainly by glutamatergic signalling.

The results of this study shows that CBD exerts rapid antidepressant-like effects as evidenced by the reversal of OBX-induced hyperactivity immediately after the first injection. Additionally, its efficacy is maintained and improved with the repeated administration, as anhedonia (inability to feel pleasure) was completely relieved after one week of treatment with a dose of 50 mg/kg. The findings also revealed a crucial role of 5-HT 1A and CB1 receptors in the behavioral and anxiolytic effects of CBD. As anxiety is a complex syndrome affected by different brain processes, the two receptors could be implicated in the anxiety outcome at different levels.

In summary, the fast onset of antidepressant action of CBD and the simultaneous anxiolytic effects, combined with the broad range for therapeutic dosage and the lack of psychotomimetic effects shows a strong therapeutic advantage for its use in clinical practice compared to other antidepressant alternatives.

Linge R, Jiménez-Sánchez L, Campa L, et al. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors. Neuopharmacology 2016;103:16-26

Modulation of Cell-Mediated Immunity to Suppress High Fat Diet-Induced Obesity and Insulin Resistance

This study was designed to test the effects that cyclosporine A and fingolimod may have on obesity caused by high fat diets and insulin resistance.  This study was conducted in mice that were fed a high fat diet, and that were regularly injected for fifteen weeks with cyclosporine A, fingolimod, or a control.

The study begins by validating its importance due to the large spike in American obesity.  The study reported that 34.9% of American adults are considered obese.  Cyclosporine A is used in organ transplant patients to help prevent the immune system from rejecting the organ.  Fingolimod, on the other hand, is used as a first-line defense in patients experiencing a relapsing form of multiple sclerosis.

Of the mice, those injected with cyclosporine A had an average body weight that was 34% less than the control mice.  Those mice treated with fingolimod were about 16% less in body weight.  They found that the cyclosporine A mice maintained weight gain suppression throughout the entire experiment, while the fingolimod mice had slowed weight gain after week 7.  To rule out the thought that there could be lean mass being lost a body composition analysis was completed using EchoMRI.  It was found that the lean mass of the mice was unaffected, but the cyclosporine A mice had 60.8% less fat mass than the control.  The fingolimod mice had about 22.2% less fat mass than the control mice.

The results of this study were that cyclosporine A and fingolimod both were able to suppress weight gain, improve the mice’s sensitivity to insulin, and reduce their hepatic fat accumulation.  It concluded that this is a promising option that should continue to be looked into and developed.

Pharmacists see countless patients suffering from diabetes type 2 and other weight related conditions.  How would an injection like this affect the way pharmacists discussed lifestyle changes and nutrition expert recommendations?  Do you feel there would be a push from patients to receive the shot rather than make changes similar to the pressure physicians feel to prescribe antibiotics?

 

Pharm Res.  2016;33(2):395-403.