Cannabinoid CB1 Receptor Expression and Localization in the Dorsal Horn of Male and Female Rat and Human Spinal Cord.

Background: Preclinical and clinical evidence suggests that cannabis has potential analgesic properties. However, cannabinoid receptor expression and localization within spinal cord pain processing circuits remain to be characterized across sex and species.

Aims: We aimed to investigate the differential expression of the cannabinoid type 1 (CB1) receptor across dorsal horn laminae and cell populations in male and female adult rats and humans.

Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain.

The prevalence and severity of many chronic pain syndromes differ across sex, and recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific pain mechanisms converge once they reach neurons within the superficial dorsal horn, direct investigations using rodent and human preclinical pain models have been lacking. Here, we discovered that in the Freund's adjuvant in vivo model of inflammatory pain, where both male and female rats display tactile allodynia, a pathological coupling between KCC2-dependent disinhibition and N-methyl-D-aspartate receptor (NMDAR) potentiation within superficial dorsal horn neurons was observed in male but not female rats.

A systematic review of the effects of cannabis on cognition in people with multiple sclerosis.

Background: Multiple sclerosis (MS) is a chronic demyelinating disease which leads to sensory, motor, autonomic, and cognitive symptoms. Cannabis is a common way for persons with MS (pwMS) to seek symptomatic therapy. Given the capacity for both cannabis and MS to cause cognitive impairment, it is important to determine whether there is any negative impact when the two co-occur.

Differential expression of GluN2 NMDA receptor subunits in the dorsal horn of male and female rats.

N-methyl-D-aspartate receptors (NMDARs) are excitatory ionotropic glutamate receptors expressed throughout the CNS, including in the spinal dorsal horn. The GluN2 subtypes of NMDAR subunit, which include GluN2A, GluN2B, and GluN2D in the dorsal horn, confer NMDARs with structural and functional variability, enabling heterogeneity in synaptic transmission and plasticity. Despite essential roles for NMDARs in physiological and pathological pain processing, the distribution and function of these specific GluN2 isoforms across dorsal horn laminae remain poorly understood.

The impact of dextran sodium sulphate and probiotic pre-treatment in a murine model of Parkinson's disease.

Background: Recent work has established that Parkinson's disease (PD) patients have an altered gut microbiome, along with signs of intestinal inflammation. This could help explain the high degree of gastric disturbances in PD patients, as well as potentially be linked to the migration of peripheral inflammatory factors into the brain. To our knowledge, this is the first study to examine microbiome alteration prior to the induction of a PD murine model.

Quantum dot conjugated saporin activates microglia and induces selective substantia nigra degeneration.

Parkinson's disease (PD) is characterized by profound microglial driven inflammatory processes and the loss of dopamine neurons of the substantia nigra (SNc). Both microglia and dopamine neurons that are affected in the SNc are particularly vulnerable to environmental toxicants and finding more selective ways of targeting these cell types is of importance. Quantum dots (QDs) might be a useful vehicle for selectively delivering toxicants to microglia and owing to their fluorescent capability, they can be microscopically tracked within the cell.

Interactive effects of ghrelin and ketamine on forced swim performance: Implications for novel antidepressant strategies.

The efficacy of ketamine to alleviate depressive symptoms has promoted a wealth of research exploring alternate therapeutic targets for depression. Given the caveats of ketamine treatment taken together with the increasingly greater emphasis on combinatorial therapeutic approaches to depression, we sought to asses whether the hypothalamic "hunger hormone", ghrelin, would augment the effects of ketamine. Indeed, ghrelin has recently been found to possess antidepressant potential and may be especially effective against the metabolic and feeding deficits observed with depression.