title: Adipokine pathways are altered in hippocampus of an experimental mouse model of Alzheimer's disease.
abstract: A growing body of evidence suggests that β-amyloid peptides (Aβ) are unlikely to be the only factor involved in Alzheimer's disease (AD) aetiology. In fact, a strong correlation has been established between AD patients and patients with type 2 diabetes and/or cholesterol metabolism alterations. In addition, a link between adipose tissue metabolism, leptin signalling in particular, and AD has also been demonstrated. In the present study we analyzed the expression of molecules related to metabolism, with the main focus on leptin and prolactin signalling pathways in an APPswe/PS1dE9 (APP/PS1) transgenic mice model, at 3 and 6 months of age, compared to wild-type controls. We have chosen to study 3 months-old APP/PS1 animals at an age when neither the cognitive deficits nor significant Aβ plaques in the brain are present, and to compare them to the 6 months-old mice, which exhibit elevated levels of Aβ in the hippocampus and memory loss. A significant reduction in both mRNA and protein levels of the prolactin receptor (PRL-R) was detected in the hippocampi of 3 months old APP/PS1 mice, with a decrease in the levels of the leptin receptor (OB-R) first becoming evident at 6 months of age. We proceeded to study the expression of the intracellular signalling molecules downstream of these receptors, including stat (1-5), sos1, kras and socs (1-3). Our data suggest a downregulation in some of these molecules such as stat-5b and socs (1-3), in 3 months-old APP/PS1 brains. Likewise, at the same age, we detected a significant reduction in mRNA levels of lrp1 and cyp46a1, both of which are involved in cholesterol homeostasis. Taken together, these results demonstrate a significative impairment in adipokine receptors signalling and cholesterol regulation pathways in the hippocampus of APP/PS1 mice at an early age, prior to the Aβ plaque formation.
authors: Antoni Camins PhD, Unitat de Farmacologia i Farmacognosia, Facultat de Farmàcia, Universitat de Barcelona, Spain. Avda/ Diagonal 643, E-08028 Barcelona, Spain. Tel: +34 93 4024531, Fax: +34 934035982, Email: camins@ub.edu.
authors: I
authors: I
authors: Pedrós
authors: D
authors: D
authors: Petrov
authors: G
authors: G
authors: Artiach
authors: S
authors: S
authors: Abad
authors: C
authors: C
authors: Ramon-Duaso
authors: F
authors: F
authors: Sureda
authors: M
authors: M
authors: Pallàs
authors: C
authors: C
authors: Beas-Zarate
authors: J
authors: J
authors: Folch
authors: A
authors: A
authors: Camins
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D000072556:Cholesterol 24-Hydroxylase; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D008569:Memory Disorders; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D020837:SOS1 Protein / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D013250:Steroid Hydroxylases / Q000235:genetics; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D054392:Adipokines; D016229:Amyloid beta-Peptides; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D012333:RNA, Messenger; D011973:Receptors, LDL; D054411:Receptors, Leptin; D011981:Receptors, Prolactin; D020837:SOS1 Protein; D050791:STAT Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins; D025521:Tumor Suppressor Proteins; D002784:Cholesterol; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase; D016283:Proto-Oncogene Proteins p21(ras)