Roles of Adenosine Receptor (subtypes A1 and A2A) in Cuprizone-Induced Hippocampal Demyelination.

Hippocampal demyelination in multiple sclerosis (MS) has been linked with cognitive deficits, however, patients could benefit from treatment that induces oligodendroglial cell function and promotes remyelination. We investigated the role of A1 and A2A adenosine receptors (AR) in regulating oligodendrocyte precursor cells (OPCs) and myelinating oligodendrocyte (OL) in the demyelinated hippocampus using the cuprizone model of MS. Spatial learning and memory were assessed in wild type C57BL/6 mice (WT) or C57BL/6 mice with global deletion of A1 (A1AR-/-) or A2A AR (A2AAR-/-) fed standard or cuprizone diet (CD) for four weeks. Histology, immunofluorescence, Western blot and TUNEL assays were performed to evaluate the extent of demyelination and apoptosis in the hippocampus. Deletion of A1 and A2A AR alters spatial learning and memory. In A1AR-/- mice, cuprizone feeding led to severe hippocampal demyelination, A2AAR-/- mice had a significant increase in myelin whereas WT mice had intermediate demyelination. The A1AR-/- CD-fed mice displayed significant astrocytosis and decreased expression of NeuN and MBP, whereas these proteins were increased in the A2AAR-/- CD mice. Furthermore, Olig2 was upregulated in A1AR-/- CD-fed mice compared to WT mice fed the standard diet. TUNEL staining of brain sections revealed a fivefold increase in the hippocampus of A1AR-/- CD-fed mice. Also, WT mice fed CD showed a significant decrease expression of A1 AR. A1 and A2A AR are involved in OPC/OL functions with opposing roles in myelin regulation in the hippocampus. Thus, the neuropathological findings seen in MS may be connected to the depletion of A1 AR.

High Environmental Temperature: Insights into Behavioural, Neurodevelopmental and Gut Microbiome Changes Following Gestational Exposure in Rats.

Adverse effects of changing climate have been associated with increase average global temperature resulting in environmental changes. We set out to investigate effects of environmental stress due to increased heat exposure on developmental milestones, behaviour, gut microbiota and neuroarchitecture in rat pups. Pregnant Wistar rats were held in standard temperature (ST) (26 ± 2 °C; control) or high temperature (HT) (40 ± 2 °C) housing. After parturition, a cohort of the HT group and their pups were moved to the control/ST housing (gestational-only-exposed pup [GE]) while the other subset remained in the HT housing (gestational and postnatal exposed pups [GE + PE]). At different time points, we examined neurodevelopmental milestones and behaviour in the pups. Following sacrifice changes in gut microbiota, neuroarchitecture, cytokine levels (TNF-α, IL-4, IL-10), SOD, MDA, expression of MBP, NeUN and GFAP were determined. We observed impaired positioning and placing of paws, prolonged righting reflex, delayed ear opening and significant decreased body weight gain in HT pups when compared with control. We identified Firmicutes and Proteobacteria and noted a significant difference in Firmicutes count between GE and GE + PE pups at P15. Furthermore, TNF-α, IL-4, IL-10 and MDA levels were increased in GE and GE + PE pups. There was also a reduction in MBP expression in the HT pups. Taken together, our results revealed a delay in neurodevelopmental milestones in pups exposed to high HT during gestation and post natal life. Pups whose dam were exposed to high HT during gestation also showed some set back but improved over the course of testing.