title: Prolonged hyperglycemia & hyperinsulinemia increases BDNF mRNA expression in the posterior ventromedial hypothalamus and the dorsomedial hypothalamus of fed female rats.
abstract: Brain-derived neurotrophic factor (BDNF) plays a key role in neuronal development, synaptic plasticity, and the central control of energy homeostasis. Peripheral metabolic signals such as leptin and glucose regulate hypothalamic BDNF gene expression. However, the effects of long-term hyperglycemia and/or hyperinsulinemia on BDNF mRNA levels in the hypothalamus and other brain regions where BDNF regulates physiological functions have not been investigated. Therefore, using in situ hybridization we examined whether high glucose, high insulin, or both affected BDNF gene expression in vivo. Ovariectomized, estrogen-replaced adult rats were fitted with indwelling jugular catheters and infused for 48 h with: saline (control), glucose (hyperglycemia-hyperinsulinemia), glucose with insulin (hyperinsulinemia only), diazoxide (Dzx) (control), or glucose with Dzx (hyperglycemia only). Glucose infusion (Hyperglycemia and hyperinsulinemia) significantly increased BDNF mRNA expression in the posterior ventromedial nucleus of the hypothalamus (pVMH) and in the dorsomedial nucleus of the hypothalamus (DMH). Unexpectedly, infusion of the KATP channel opener Dzx also increased BDNF mRNA expression in the pVMH and DMH. In contrast, no significant changes in BDNF mRNA expression were observed in the groups that were hyperinsulinemic only or hyperglycemic only. BDNF mRNA expression did not differ as a function of treatment in the anterior VMH, paraventricular nucleus of the hypothalamus, the hippocampus, or the amygdala. Hyperglycemia with and without hyperinsulinemia decreased BDNF mRNA levels in the pituitary. Plasma BDNF concentrations were not changed by any of the treatments. Our results suggest that hyperinsulinemia alone does not affect BDNF mRNA expression in the hypothalamus, hippocampus, or pituitary. Our study is the first to distinguish that within the hypothalamus, prolonged high glucose levels in non-fasted rats regulates BDNF gene expression in a brain nuclei-specific fashion.
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Medical Center, Stony Brook, NY, United States; Graduate Program in Neuroscience, Stony Brook University, Stony Brook, NY, United States.
authors.forename: A L
authors.initials: AL
authors.lastname: Negrón
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Medical Center, Stony Brook, NY, United States; Graduate Program in Genetics, Stony Brook University, Stony Brook, NY, United States.
authors.forename: M
authors.initials: M
authors.lastname: Beymer
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Medical Center, Stony Brook, NY, United States.
authors.forename: G
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Medical Center, Stony Brook, NY, United States.
authors.forename: K A
authors.initials: KA
authors.lastname: Warren
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Medical Center, Stony Brook, NY, United States. Electronic address: Maricedes.acosta@stonybrook.edu.
authors.forename: M
authors.initials: M
authors.lastname: Acosta-Martínez
mesh_terms: D000818:Animals; D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000009:adverse effects; D006943:Hyperglycemia / Q000139:chemically induced / Q000473:pathology*; D006946:Hyperinsulinism / Q000209:etiology / Q000473:pathology*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007986:Luteinizing Hormone / Q000378:metabolism; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D007328:Insulin; D012333:RNA, Messenger; D014665:Vasodilator Agents; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005947:Glucose; D003981:Diazoxide
keywords: brain-derived neurotrophic factor (BDNF); diazoxide; glucose; hyperglycemia; hypothalamus; insulin