Caudal brainstem Fos expression is restricted to periventricular catecholamine neuron-containing loci following intraventricular administration of 2-deoxy- d -glucose

Abstract

Reports that food intake is stimulated by fourth ventricular administration of glucose antimetabolites or uptake inhibitors suggest that glucose deprivation within the periventricular caudal brainstem activates compensatory neural mechanisms that restore global metabolic stasis. In the present study, Fos immunocytochemistry was employed to characterize the distribution of neurons within this region of the male rat brain that undergo genomic activation in response to intraventricular delivery of the antiglycolytic agent, 2-deoxy-D-glucose (2DG). Fos immunoreactivity (-ir) was only detected in the locus coeruleus (LC), nucleus of the solitary tract (NTS), and area postrema (AP) following drug treatment, whereas immunostaining for Fos was absent from these structures in the vehicle-treated control group. Dual-label immunocytochemical processing of sections of these loci for Fos- and tyrosine hydroxylase (TH)-ir revealed that, in each site, a majority of TH-ir-positive neurons were co-labeled for this nuclear protein in response to this treatment paradigm. These results provide evidence for the transcriptional activation of catecholaminergic neurons in discrete periventricular caudal brainstem structures during central glucopenia. Taken together with pharmacological evidence for the initiation of glucoprivic regulatory signaling within neural tissue accessible from the fourth ventricle, the present findings suggest that LC A6, NTS precommissural C2 and commissural A2, and AP TH-ir-positive neurons may function to monitor and/or signal alterations in periventricular glucose metabolism as a means of defending central substrate balance.

Neuronal activation of brain vagal-regulatory pathways and upper gut enteric plexuses by insulin hypoglycemia

“…Our findings indicate that the LC may also participate in the central vagal response to hypoglycemia. In support of this indication, it has been reported that the LC sends direct projections to the medullary DMN (66), and intracerebroventricular injection of 2-DG induces Fos expression in the TH neurons of the NTS and LC (7).…”

“…It is interesting to note that, when serum glucose levels dropped below 80 mg/dl, Fos expression began to increase in these vagal-regulatory nuclei and further increased along with the decrease of glucose levels. Confirmation that the brain Fos induction by insulin hypoglycemia was related to hypoglycemia-induced cellular energy deficiency comes from the fact that acute glucose deprivation induced by 2-deoxyglucose (2-DG) induced similar vagal-mediated stimulation on visceral functions (32) and Fos expression in the PVN, DMN, and NTS (7,59). Finally, the observation that glucose microinjected into the DVC or injected into the portal vein inhibited insulin hypoglycemia-induced gastric acid secretion and motility (57,58) provides additional support for this view.…”

Hindbrain Neuroglucopenia Elicits Site-Specific Transcriptional Activation of Glutamate Decarboxylase-Immunopositive Neurons in the Septopreoptic Area of Female Rat Brain

“…NTS and dorsal vagal motor nucleus, and the adjacent area postrema (AP), and are characterized by a catecholaminergic phenotype in the NTS [27,28,29]. Corroborative studies in our laboratory have demonstrated immediate-early gene expression by tyrosine hydroxylase-immunopositive neurons in the NTS/AP in response to pharmacological induction of local glucopenia [30]. While the NTS provides both direct and indirect innervation to the ARH [31], the neuroanatomical and neurochemical mechanisms by which hindbrain signaling of neuroglucopenia may be conveyed to POMC neurons in the latter site remain unclear.…”

Transcriptional Activation of Nucleus tractus solitarii/Area postrema Catecholaminergic Neurons by Pharmacological Inhibition of Caudal Hindbrain Monocarboxylate Transporter Function

“…Catecholaminergic (CA) neurons in this neural structure are a logical focus of inquiry, since these cells are electrophysiologically and genomically responsive to glucose deficits [14,15,16], and it is reported that metabolically ‘sensitive’ neurons in the NTS/AP respond in a similar manner to alterations in glucose and lactate availability [13]. The present studies therefore investigated the role of NTS/AP CA neurons in signaling of lactate deficits by examining whether pharmacological inhibition of lactate transport in the caudal hindbrain by 4-CIN elicits transcriptional activation of these cells.…”