title: BDNF and AMPA receptors in the cNTS modulate the hyperglycemic reflex after local carotid body NaCN stimulation.
abstract: The application of sodium cyanide (NaCN) to the carotid body receptors (CBR) (CBR stimulation) induces rapid blood hyperglycemia and an increase in brain glucose retention. The commissural nucleus tractus solitarius (cNTS) is an essential relay nucleus in this hyperglycemic reflex; it receives glutamatergic afferents (that also release brain derived neurotrophic factor, BDNF) from the nodose-petrosal ganglia that relays CBR information. Previous work showed that AMPA in NTS blocks hyperglycemia and brain glucose retention after CBR stimulation. In contrast, BDNF, which attenuates glutamatergic AMPA currents in NTS, enhances these glycemic responses. Here we investigated the combined effects of BDNF and AMPA (and their antagonists) in NTS on the glycemic responses to CBR stimulation. Microinjections of BDNF plus AMPA into the cNTS before CBR stimulation in anesthetized rats, induced blood hyperglycemia and an increase in brain arteriovenous (a-v) of blood glucose concentration difference, which we infer is due to increased brain glucose retention. By contrast, the microinjection of the TrkB antagonist K252a plus AMPA abolished the glycemic responses to CBR stimulation similar to what is observed after AMPA pretreatments. In BDNF plus AMPA microinjections preceding CBR stimulation, the number of c-fos immunoreactive cNTS neurons increased. In contrast, in the rats microinjected with K252a plus AMPA in NTS, before CBR stimulation, c-fos expression in cNTS decreased. The expression of AMPA receptors GluR2/3 did not change in any of the studied groups. These results indicate that BDNF in cNTS plays a key role in the modulation of the hyperglycemic reflex initiated by CBR stimulation.
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Ave. 25 de Julio 965, Colima 28045, Mexico; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Guadalajara 44340, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Cuéllar
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Ave. 25 de Julio 965, Colima 28045, Mexico; Facultad de Medicina, Universidad de Colima, Ave. Universidad 333, Colima 28040, Mexico.
authors.forename: S
authors.initials: S
authors.lastname: Montero
authors.affiliation: Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Guadalajara 44340, Mexico.
authors.forename: S
authors.initials: S
authors.lastname: Luquín
authors.affiliation: Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Guadalajara 44340, Mexico; División de Investigación Quirúrgica, Centro de Investigación Biomédica de Occidente, IMSS, Guadalajara, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: García-Estrada
authors.affiliation: Facultad de Medicina, Universidad de Colima, Ave. Universidad 333, Colima 28040, Mexico.
authors.forename: V
authors.initials: V
authors.lastname: Melnikov
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Ave. 25 de Julio 965, Colima 28045, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Virgen-Ortiz
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Ave. 25 de Julio 965, Colima 28045, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Lemus
authors.affiliation: Facultad de Medicina, Universidad de Colima, Ave. Universidad 333, Colima 28040, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Pineda-Lemus
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Ave. 25 de Julio 965, Colima 28045, Mexico. Electronic address: rab@ucol.mx.
authors.forename: E
authors.initials: E
authors.lastname: de Álvarez-Buylla
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism*; D002344:Carotid Body / Q000187:drug effects* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D018377:Neurotransmitter Agents / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012966:Sodium Cyanide / Q000494:pharmacology; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018377:Neurotransmitter Agents; D016760:Proto-Oncogene Proteins c-fos; D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C000621230:Ntrk2 protein, rat; D020813:Receptor, trkB; D005947:Glucose; D012966:Sodium Cyanide
keywords: AMPA receptor; AMPA type glutamate receptors; Brain glucose retention; Brain-derived neurotrophic factor; CBR NaCN local application; Commissural nucleus tractus solitarius (cNTS); Hyperglycemic reflex