title: Reduced intestinal brain-derived neurotrophic factor increases vagal sensory innervation of the intestine and enhances satiation.
abstract: Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF(-/-)) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF(-/-) mice were increased, but stomach IGLEs were normal. INT-BDNF(-/-) mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF(-/-) mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF(-/-) mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF(-/-) mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF(-/-) mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF(-/-) mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation.
authors: Behavioral Neurogenetics Laboratory, Department of Psychological Sciences, Purdue University, West Lafayette, Indiana 47907.
authors: Jessica E
authors: JE
authors: Biddinger
authors: Behavioral Neurogenetics Laboratory, Department of Psychological Sciences, Purdue University, West Lafayette, Indiana 47907 au_gc@psych.purdue.edu.
authors: Edward A
authors: EA
authors: Fox
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000502:physiology; D001823:Body Composition / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency* / Q000235:genetics; D004435:Eating / Q000235:genetics; D005247:Feeding Behavior / Q000502:physiology; D007422:Intestines / Q000294:innervation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D009475:Neurons, Afferent / Q000502:physiology*; D009620:Nodose Ganglion / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012527:Satiation / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008840:Microfilament Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C058992:Tagln protein, mouse; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
keywords: food intake; growth factor; ingestive behavior; meal patterns; nodose ganglion; vagus nerve