Activity-based anorexia activates nesfatin-1 immunoreactive neurons in distinct brain nuclei of female rats.

Activity-based anorexia (ABA) is an established animal model for the eating disorder anorexia nervosa (AN). The pathophysiology of AN and the involvement of food intake-regulatory peptides is still poorly understood. Nesfatin-1, an anorexigenic peptide also involved in the mediation of stress, anxiety and depression might be a likely candidate involved in the pathogenesis of AN. Therefore, activation of nesfatin-1 immunoreactive (ir) brain nuclei was investigated under conditions of ABA. Female Sprague-Dawley rats were used and divided into four groups (n=6/group): activity-based anorexia (ABA), restricted feeding (RF), activity (AC) and ad libitum fed (AL). After the 21-day experimental period and development of ABA, brains were processed for c-Fos/nesfatin-1 double labeling immunohistochemistry. ABA increased the number of nesfatin-1 immunopositive neurons in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, locus coeruleus and in the rostral part of the nucleus of the solitary tract compared to AL and AC groups (p<0.05) but not to RF rats (p>0.05). Moreover, we observed significantly more c-Fos and nesfatin-1 ir double-labeled cells in ABA rats compared to RF, AL and AC in the supraoptic nucleus (p<0.05) and compared to AL and AC in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, dorsal raphe nucleus and the rostral raphe pallidus (p<0.05). Since nesfatin-1 plays a role in the inhibition of food intake and the response to stress, we hypothesize that the observed changes of brain nesfatin-1 might play a role in the pathophysiology and symptomatology under conditions of ABA and potentially also in patients with AN.

Differential distribution of individual subunits of strongly inwardly rectifying potassium channels (Kir2 family) in rat brain.

Inwardly rectifying potassium (Kir) channels modulate cellular excitability, membrane potential, and secretion of neurotransmitters and hormones. Kir channels with the strongest inward rectification belong to the Kir2 family. In this report, polyclonal monospecific affinity-purified antibodies against the less conserved carboxy-terminal sequences of Kir2.1, Kir2.2, Kir2.3, and Kir2.4 were used to analyze the detailed distribution of all members of the Kir2 family in the rat central nervous system. Kir2 channel expression is detected in neurons but not in glial cells. Kir2 protein distribution confirms the basic mRNA localization pattern given by in situ hybridization. Kir2.1 is detected throughout the whole brain but in particular subsets of neurons with highest expression in olfactory bulb and superior colliculus. Kir2.2 immunoreactivity is primarily displayed in several forebrain nuclei, hypothalamus, cerebellum, and spinal cord. The Kir2.3 subunit is predominantly localized in olfactory bulb, basal ganglia, cortex, and cerebellar Purkinje cells. In contrast, Kir2.4-positive staining is detected at significantly lower levels in most neurons throughout the rat brain with highest expression in brainstem motoneurons. Thus, our data show a more widespread distribution of Kir2.4 than previously determined. In summary, the widespread presence of all four Kir2 channel subunits in the rat brain provides further evidence for their important role in central signal processing and neural transmission.