title: The beneficial effects of leptin on REM sleep deprivation-induced cognitive deficits in mice.
abstract: Leptin, a 167 amino acid peptide, is synthesized predominantly in the adipose tissues and plays a key role in the regulation of food intake and body weight. Recent studies indicate that leptin receptor is expressed with high levels in many brain regions that may regulate synaptic plasticity. Here we show that deprivation of rapid eye movement (REMD) sleep resulted in impairment of both cue and contextual fear memory. In parallel, surface expression of GluR1 was reduced in the amygdala. Intraperitoneal injection of leptin to the REMD mice rescued memory impairment and reversed surface GluR1 reduction. Using whole-cell recording to evaluate the synaptic function of the thalamus-lateral amygdala (LA) pathway, we found a decrease in frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) concomitant with reduced AMPA/NMDA ratios in the REMD mice. By contrast, paired-pulse facilitation (PPF) was increased. The effects of REMD on mEPSCs and AMPA/NMDA ratio could be reversed by leptin treatment, whereas on PPR it could not. Phosphatase and tensin homolog (PTEN), a dual protein/lipid phosphatase, down-regulates the effect of the PI-3 kinase pathway. Fear conditioning increased whereas REMD led to a decrease in the phosphorylated states of PTEN, Akt, and glycogen synthase kinase-3β (GSK3β), and the effects of REMD were reversed by leptin. These results suggest that both pre- and postsynaptic functions of the thalamus-LA pathway were altered by fear conditioning and REMD in opposite directions. Leptin treatment reversed REMD-induced memory deficits primarily by a postsynaptic action by restoring surface expression of GluR1 without affecting PPR.
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan 701.
authors.forename: Hsiao-Fu
authors.initials: HF
authors.lastname: Chang
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Su
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Chang
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Po-Wu
authors.initials: PW
authors.lastname: Gean
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D003214:Conditioning, Classical; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D012892:Sleep Deprivation / Q000150:complications* / Q000378:metabolism*
chemical_list: D020738:Leptin