Swimming exercise versus L-carnosine supplementation for Alzheimer's dementia in rats: implication of circulating and hippocampal FNDC5/irisin.

Recent studies have suggested that irisin may act as a potential neurokine. Exercise and L-carnosine supplementation showed neuroprotective effects in Alzheimer's disease (AD)-like conditions. However, the regulation of irisin in the hippocampus of streptozotocin (STZ)-induced memory impairment and its relation to insulin signalling remain to be investigated. This study was designed to compare the effect of swimming exercise and L-carnosine intake on serum, CSF and hippocampal irisin in rats received intracerebroventricular (ICV) injection of STZ. Rats were recruited in swimming paradigm, received oral carnosine (100 mg/kg/day) or vehicle treated. After 5 weeks, rats were sacrificed after neurobehavioural testing. CSF and serum irisin were determined. Hippocampal tissues were used to assess expression of FNDC5/irisin, BDNF and proteins related to insulin signalling, in addition to ß-amyloid peptide and phosphorylated tau protein levels. We observed decreased hippocampal, but not CSF or serum, irisin in ICV-STZ-injected rats. Exercise and carnosine intake almost normalized hippocampal FNDC5/irisin expression which was associated with reduced soluble ß-amyloid peptide and phosphorylated tau protein, improved BDNF and insulin signalling proteins, with corresponding mitigated cognitive impairments. However, hippocampal FNDC5/irisin was not correlated with serum or CSF irisin levels. Histologically, both interventions ameliorated the hippocampal damage in STZ-injected rats. The current study reveals that carnosine is equivalent to exercise in reversing cognitive decline and Alzheimer's biomarkers. In both interventions, enhancement of hippocampal FNDC5/irisin and insulin signalling may be involved in mediating these neuroprotective effects.

Crosstalk of hypothalamic chemerin, histamine, and AMPK in diet-and olanzapine-induced obesity in rats.

AIM: Contradiction overwhelms chemerin link to feeding behavior. Neither the chemerin central role on appetite regulation nor its relation to hypothalamic histamine and AMPK is verified. MAIN METHODS: Food intake, body weight and hypothalamic biochemical changes were assessed after a single intra-cerebroventricular or intraperitoneal injection (ip) (1 µg/kg or 16 µg/kg, respectively) or chronic ip administration (8 µg/kg/day) of chemerin for 14 or 28 days. Hypothalamic neurobiochemical changes in chemerin/histamine/AMPK induced by either 8-week high fat diet (HFD) or food restriction were also investigated. To confirm chemerin-histamine crosstalk, these neurobiochemical changes were assessed under settings of H1-receptor agonism and/or antagonism by betahistine and/or olanzapine, respectively for 3 weeks. KEY FINDINGS: Chemerin-injected rats exhibited anorexigenic behavior in both acute and chronic studies that was associated with a decreased AMPK activity in the arcuate nucleus (ARC). However, with long-term administration, chemerin anorexigenic effect gradually ceased. Contrarily to food restriction, 8-week HFD increased ARC expression of chemerin and its receptor CMKLR1, reducing food intake via an interplay of H1-receptors and AMPK activity. Blockage of H1-receptors by olanzapine disrupted chemerin signaling pathway with an increased AMPK activity, augmenting food intake. These changes were reversed to normal by betahistine coadministration. SIGNIFICANCE: Chemerin is an anorexigenic adipokine, whose dysregulation is implicated in diet, and olanzapine-induced obesity through a histamine/AMPK axis in the ARC. Hypothalamic chemerin/CMKLR1 expression is a dynamic time-dependent response to changes in body weight and/or food intake. Targeting chemerin as a novel therapeutic approach against antipsychotic- or diet-induced obesity is worth to be further delineated.