Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice

Vigneshwaran Pitchaimani; Somasundaram Arumugam; Rajarajan Amirthalingam Thandavarayan; Vengadeshprabhu Karuppagounder; Remya Sreedhar; Rejina Afrin; Meilei Harima; Hiroshi Suzuki; Shizuka Miyashita; Mayumi Nomoto; Hirohito Sone; Kenji Suzuki; Kenichi Watanabe

doi:10.1016/j.neulet.2014.07.009

Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice

Neurosci Lett. 2014 Sep 5:579:134-9. doi: 10.1016/j.neulet.2014.07.009. Epub 2014 Jul 17.

Affiliations

¹ Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
² Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan; Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX 77030, USA.
³ Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan; Department of Hematology, Endocrinology and Metabolism, Niigata City 951-8510, Japan.
⁴ Department of Hematology, Endocrinology and Metabolism, Niigata City 951-8510, Japan.
⁵ Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City 951-8510, Japan.
⁶ Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan. Electronic address: watanabe@nupals.ac.jp.

PMID: 25043191
DOI: 10.1016/j.neulet.2014.07.009

Abstract

BAD-deficient mice and fasting have several common functional roles in seizures, beta-hydroxybutyrate (BHB) uptake in brain and alteration in counterregulatory hormonal regulation during hypoglycemia. Neuronal specific insulin receptor knockout (NIRKO) mice display impaired counterregulatory hormonal responses during hypoglycemia. In this study we investigated the fasting mediated expression of p-BAD(ser155) and p-AKT(ser473) in different regions of brain (prefrontal cortex, hippocampus, midbrain and hypothalamus). Fasting specifically increases p-BAD(ser155) and p-AKT(ser473) in prefrontal cortex and decreases in other regions of brain. Our results suggest that fasting may increase the uptake BHB by decreasing p-BAD(ser155) in the brain during hypoglycemia except prefrontal cortex and it uncovers specific functional area of p-BAD(ser155) and p-AKT(ser473) that may regulates counter regulatory hormonal response. Overall in support with previous findings, fasting mediated hypoglycemia activates prefrontal cortex insulin signaling which influences the hypothalamic paraventricular nucleus mediated activation of sympathoadrenal hormonal responses.

Keywords: AKT; BAD; Betahydroxybutyrate; Fasting; Hypoglycemia; Prefrontal cortex.

Publication types

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

MeSH terms

Animals
Blood Glucose / metabolism
Brain Chemistry / genetics
Fasting / metabolism*
Insulin / physiology
Liver / metabolism
Mice
Mice, Knockout
Oncogene Protein v-akt / biosynthesis*
Oncogene Protein v-akt / genetics
Prefrontal Cortex / metabolism*
Receptor, Insulin / genetics
Signal Transduction / genetics
bcl-Associated Death Protein / biosynthesis*
bcl-Associated Death Protein / genetics

Substances

Bad protein, mouse
Blood Glucose
Insulin
bcl-Associated Death Protein
Receptor, Insulin
Oncogene Protein v-akt