Hepatic-portal vein infusions of glucagon-like peptide-1 reduce meal size and increase c-Fos expression in the nucleus tractus solitarii, area postrema and central nucleus of the amygdala in rats

We recently reported that brief, remotely controlled intrameal hepatic-portal vein infusions of glucagon-like peptide-1 (GLP-1) reduced spontaneous meal size in rats. To investigate the neurobehavioural correlates of this effect, we equipped male Sprague-Dawley rats with hepatic-portal vein catheters and assessed (i) the effect on eating of remotely triggered infusions of GLP-1 (1 nmol/kg, 5 min) or vehicle during the first nocturnal meal after 3 h of food deprivation and (ii) the effect of identical infusions performed at dark onset on c-Fos expression in several brain areas involved in the control of eating. GLP-1 reduced (P < 0.05) the size of the first nocturnal meal and increased its satiety ratio. Also, GLP-1 increased (P < 0.05) the number of c-Fos-expressing cells in the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala, but not in the arcuate or paraventricular hypothalamic nuclei. These data suggest that the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala play a role in the eating-inhibitory actions of GLP-1 infused into the hepatic-portal vein; it remains to be established whether activation of these brain nuclei reflect satiation, aversion, or both.

Spastin in the human and mouse central nervous system with special reference to its expression in the hippocampus of mouse pilocarpine model of status epilepticus and temporal lobe epilepsy

In the present in situ hybridization and immunocytochemical studies in the mouse central nervous system (CNS), a strong expression of spastin mRNA and protein was found in Purkinje cells and dentate nucleus in the cerebellum, in hippocampal principal cells and hilar neurons, in amygdala, substantia nigra, striatum, in the motor nuclei of the cranial nerves and in different layers of the cerebral cortex except piriform and entorhinal cortices where only neurons in layer II were strongly stained. Spastin protein and mRNA were weakly expressed in most of the thalamic nuclei. In selected human brain regions such as the cerebral cortex, cerebellum, hippocampus, amygdala, substania nigra and striatum, similar results were obtained. Electron microscopy showed spastin immunopositive staining in the cytoplasma, dendrites, axon terminals and nucleus. In the mouse pilocarpine model of status epilepticus and subsequent temporal lobe epilepsy, spastin expression disappeared in hilar neurons as early as at 2h during pilocarpine induced status epilepticus, and never recovered. At 7 days and 2 months after pilocarpine induced status epilepticus, spastin expression was down-regulated in granule cells in the dentate gyrus, but induced expression was found in reactive astrocytes. The demonstration of widespread distribution of spastin in functionally different brain regions in the present study may provide neuroanatomical basis to explain why different neurological, psychological disorders and cognitive impairment occur in patients with spastin mutation. Down-regulation or loss of spastin expression in hilar neurons may be related to their degeneration and may therefore initiate epileptogenetic events, leading to temporal lobe epilepsy.