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The Protective Effects of IGF-I against β-Amyloid-related Downregulation of Hippocampal Somatostatinergic System Involve Activation of Akt and Protein Kinase A.
Neuroscience 2018; 374:104-118N

Abstract

Somatostatin (SRIF), a neuropeptide highly distributed in the hippocampus and involved in learning and memory, is markedly reduced in the brain of Alzheimer's disease patients. The effects of insulin-like growth factor-I (IGF-I) against β amyloid (Aβ)-induced neuronal death and associated cognitive disorders have been extensively reported in experimental models of this disease. Here, we examined the effect of IGF-I on the hippocampal somatostatinergic system in Aβ-treated rats and the molecular mechanisms associated with changes in this peptidergic system. Intracerebroventricular Aβ25-35 administration during 14 days (300 pmol/day) to male rats increased Aβ25-35 levels and cell death and markedly reduced SRIF and SRIF receptor 2 levels in the hippocampus. These deleterious effects were associated with reduced Akt and cAMP response element-binding protein (CREB) phosphorylation and activation of c-Jun N-terminal kinase (JNK). Subcutaneous IGF-I co-administration (50 µg/kg/day) reduced hippocampal Aβ25-35 levels, cell death and JNK activation. In addition, IGF-I prevented the reduction in the components of the somatostatinergic system affected by Aβ infusion. Its co-administration also augmented protein kinase A (PKA) activity, as well as Akt and CREB phosphorylation. These results suggest that IGF-I co-administration may have protective effects on the hippocampal somatostatinergic system against Aβ insult through up-regulation of PKA activity and Akt and CREB phosphorylation.

Authors+Show Affiliations

Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain; Unidad Predepartamental de Medicina, Universidad Jaume I, Castellón, Spain.Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain; CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain; CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain.Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain; CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain; CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain; IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.Department of Physiology, Medical School, Universidad de Alcalá, Alcalá de Henares, Spain.Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain; CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: vicente.barriossa@salud.madrid.org.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29406271

Citation

Aguado-Llera, David, et al. "The Protective Effects of IGF-I Against β-Amyloid-related Downregulation of Hippocampal Somatostatinergic System Involve Activation of Akt and Protein Kinase A." Neuroscience, vol. 374, 2018, pp. 104-118.
Aguado-Llera D, Canelles S, Frago LM, et al. The Protective Effects of IGF-I against β-Amyloid-related Downregulation of Hippocampal Somatostatinergic System Involve Activation of Akt and Protein Kinase A. Neuroscience. 2018;374:104-118.
Aguado-Llera, D., Canelles, S., Frago, L. M., Chowen, J. A., Argente, J., Arilla, E., & Barrios, V. (2018). The Protective Effects of IGF-I against β-Amyloid-related Downregulation of Hippocampal Somatostatinergic System Involve Activation of Akt and Protein Kinase A. Neuroscience, 374, pp. 104-118. doi:10.1016/j.neuroscience.2018.01.041.
Aguado-Llera D, et al. The Protective Effects of IGF-I Against β-Amyloid-related Downregulation of Hippocampal Somatostatinergic System Involve Activation of Akt and Protein Kinase A. Neuroscience. 2018 03 15;374:104-118. PubMed PMID: 29406271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Protective Effects of IGF-I against β-Amyloid-related Downregulation of Hippocampal Somatostatinergic System Involve Activation of Akt and Protein Kinase A. AU - Aguado-Llera,David, AU - Canelles,Sandra, AU - Frago,Laura M, AU - Chowen,Julie A, AU - Argente,Jesús, AU - Arilla,Eduardo, AU - Barrios,Vicente, Y1 - 2018/02/03/ PY - 2017/09/12/received PY - 2017/12/14/revised PY - 2018/01/18/accepted PY - 2018/2/7/pubmed PY - 2018/11/21/medline PY - 2018/2/7/entrez KW - Alzheimer’s disease KW - IGF-I KW - hippocampus KW - protein kinase A KW - somatostatin KW - β-amyloid SP - 104 EP - 118 JF - Neuroscience JO - Neuroscience VL - 374 N2 - Somatostatin (SRIF), a neuropeptide highly distributed in the hippocampus and involved in learning and memory, is markedly reduced in the brain of Alzheimer's disease patients. The effects of insulin-like growth factor-I (IGF-I) against β amyloid (Aβ)-induced neuronal death and associated cognitive disorders have been extensively reported in experimental models of this disease. Here, we examined the effect of IGF-I on the hippocampal somatostatinergic system in Aβ-treated rats and the molecular mechanisms associated with changes in this peptidergic system. Intracerebroventricular Aβ25-35 administration during 14 days (300 pmol/day) to male rats increased Aβ25-35 levels and cell death and markedly reduced SRIF and SRIF receptor 2 levels in the hippocampus. These deleterious effects were associated with reduced Akt and cAMP response element-binding protein (CREB) phosphorylation and activation of c-Jun N-terminal kinase (JNK). Subcutaneous IGF-I co-administration (50 µg/kg/day) reduced hippocampal Aβ25-35 levels, cell death and JNK activation. In addition, IGF-I prevented the reduction in the components of the somatostatinergic system affected by Aβ infusion. Its co-administration also augmented protein kinase A (PKA) activity, as well as Akt and CREB phosphorylation. These results suggest that IGF-I co-administration may have protective effects on the hippocampal somatostatinergic system against Aβ insult through up-regulation of PKA activity and Akt and CREB phosphorylation. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/29406271/The_Protective_Effects_of_IGF_I_against_β_Amyloid_related_Downregulation_of_Hippocampal_Somatostatinergic_System_Involve_Activation_of_Akt_and_Protein_Kinase_A_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(18)30071-X DB - PRIME DP - Unbound Medicine ER -