Glucose metabolism links astroglial mitochondria to cannabinoid effects.

Astrocytes take up glucose from the bloodstream to provide energy to the brain, thereby allowing neuronal activity and behavioural responses1-5. By contrast, astrocytes are under neuronal control through specific neurotransmitter receptors5-7. However, whether the activation of astroglial receptors can directly regulate cellular glucose metabolism to eventually modulate behavioural responses is unclear. Here we show that activation of mouse astroglial type-1 cannabinoid receptors associated with mitochondrial membranes (mtCB1) hampers the metabolism of glucose and the production of lactate in the brain, resulting in altered neuronal functions and, in turn, impaired behavioural responses in social interaction assays. Specifically, activation of astroglial mtCB1 receptors reduces the phosphorylation of the mitochondrial complex I subunit NDUFS4, which decreases the stability and activity of complex I. This leads to a reduction in the generation of reactive oxygen species by astrocytes and affects the glycolytic production of lactate through the hypoxia-inducible factor 1 pathway, eventually resulting in neuronal redox stress and impairment of behavioural responses in social interaction assays. Genetic and pharmacological correction of each of these effects abolishes the effect of cannabinoid treatment on the observed behaviour. These findings suggest that mtCB1 receptor signalling can directly regulate astroglial glucose metabolism to fine-tune neuronal activity and behaviour in mice.

Loss of the neurodevelopmental gene Zswim6 alters striatal morphology and motor regulation.

The zinc-finger SWIM domain-containing protein 6 (ZSWIM6) is a protein of unknown function that has been associated with schizophrenia and limited educational attainment by three independent genome-wide association studies. Additionally, a putatively causal point mutation in ZSWIM6 has been identified in several cases of acromelic frontonasal dysostosis with severe intellectual disability. Despite the growing number of studies implicating ZSWIM6 as an important regulator of brain development, its role in this process has never been examined. Here, we report the generation of Zswim6 knockout mice and provide a detailed anatomical and behavioral characterization of the resulting phenotype. We show that Zswim6 is initially expressed widely during embryonic brain development but becomes restricted to the striatum postnatally. Loss of Zswim6 causes a reduction in striatal volume and changes in medium spiny neuron morphology. These changes are associated with alterations in motor control, including hyperactivity, impaired rotarod performance, repetitive movements, and behavioral hyperresponsiveness to amphetamine. Together, our results show that Zswim6 is indispensable to normal brain function and support the notion that Zswim6 might serve as an important contributor to the pathogenesis of schizophrenia and other neurodevelopmental disorders.

The Community Balance and Mobility Scale: A VALID ASSESSMENT TOOL OF BALANCE IN CARDIAC REHABILITATION PATIENTS.

PURPOSE: Many patients participating in cardiac rehabilitation (CR) programs have decreased balance. This is a concern, as it may affect their ability to optimally perform physical exercise in CR and thus decrease CR efficacy. Despite this concern, balance is typically not assessed as part of CR intake. This may be attributable to the fact that a suitable balance assessment tool has not been identified for higher-functioning CR patients. A potential solution to this issue is using the Community Balance and Mobility Scale (CBMS), which has been used to assess balance in higher-functioning clinical populations; however, its use in a CR population has never been investigated. Therefore, the purpose of this study was to determine the reliability and validity of the CBMS for assessing balance in CR patients. METHODS: Fifty-three participants were recruited from local CR programs to perform the CBMS. Dynamic posturography was also measured in a subset of participants (n = 31) using the Limits of Stability (LOS) test. RESULTS: Analysis of CBMS scores revealed that the mean CBMS score was 61.9 ± 16.2 (out of 96) and that no floor or ceiling effects were observed for any participants. CBMS scores were significantly correlated with the LOS results (0.41-0.53). Interrater reliability between novice and expert testers was strong (r = 0.95), with all differences falling within the 95% limits of agreement. CONCLUSION: Overall, these results suggest that the CBMS is a valid tool to measure balance in CR patients and can be reliably administered by health care professionals with minimal training.