Unilateral cortical application of interleukin-1beta (IL1beta) induces asymmetry in fos, IL1beta and nerve growth factor immunoreactivity: implications for sleep regulation.

Unilateral injection of interleukin-1 beta (IL1beta) into the somatosensory cortex enhances EEG slow wave activity ipsilaterally during non-rapid eye movement sleep [Yasuda, T., Yoshida, H., Garcia-Garcia, F., Kay, D., Krueger, J.M., 2005. Interleukin-1beta has a role in cerebral cortical state-dependent electroencephalographic slow-wave activity. Sleep 28, 177-184]. We show that a similar unilateral microinjection of IL1beta (10 ng) into layer VI or onto the surface of the primary somatosensory cortex induced increases in the neuronal activity marker, Fos, relative to the contralateral side that received saline or heat-inactivated IL1beta. When IL1beta was microinjected into layer VI, increases in Fos-immunoreactive nuclei were evident in layers II, III and VI of the somatosensory cortex and connected cortical regions, such as the endopiriform, secondary somatosensory, piriform and prefrontal cortex. Asymmetrical increases in Fos were also observed in subcortical regions, such as the reticular thalamus, which receives a main cortical projection, and hypothalamic regions implicated in sleep regulation, such as the ventrolateral preoptic area and dorsal median preoptic nucleus. Fos activation was not observed in many other brain regions. In the reticular thalamus and somatosensory cortex, the number of IL1beta-immunoreactive glial cells increased. Further, the number of NGF-immunoreactive cells in the primary somatosensory cortex and magnocellular preoptic nucleus increased on the IL1beta-injected side. These results are consistent with the hypothesis that sleep is initiated within the cortex after the local activation of specific cytokines and that whole organism sleep is coordinated via cortical connections with the subcortical sites.

Unilateral cortical application of tumor necrosis factor alpha induces asymmetry in Fos- and interleukin-1beta-immunoreactive cells within the corticothalamic projection.

A unilateral microinjection of tumor necrosis factor alpha (TNFalpha) (150 ng) onto the primary somatosensory cortex induces state-dependent asymmetries in electroencephalographic (EEG) slow wave activity during non-rapid eye movement sleep in rats [H. Yoshida, Z. Peterfi, F. Garcia-Garcia, R. Kirkpatrick, T. Yasuda, J.M. Krueger, State-specific asymmetries in EEG slow wave activity induced by local application of TNF alpha, Brain Res. 1009 (2004) 129-136]. In the current study, analogous TNFalpha injections were performed to determine Fos- and interleukin-1beta (IL1beta) immunoreactivity (IR). A unilateral microinjection of TNFalpha increased the number of Fos- and IL1beta-IR cells in the primary somatosensory cortex relative to the contralateral side that received heat-inactivated TNFalpha. These asymmetric TNFalpha-induced increases in the number of Fos- and IL1beta-IR cells were evident along the outside surface of the cortex (mainly layers II and III) in a restricted rostral to caudal zone. Asymmetrical increases in the number of Fos-IR cells were also observed in the subcortical region that receives the main cortical projection from the somatosensory cortex, the somatic region of the reticular nucleus of the thalamus (reticular thalamus). The IL1beta-IR cells double-labeled with glial fibrillary acidic protein (GFAP), suggesting that many of the IL1beta-IR cells were astrocytes. The number of the IL1beta-IR cells in the reticular thalamus increased significantly ipsilateral to the TNFalpha injection. Current results indicated that Fos- and IL1beta-IR may be utilized to study the functional neuroanatomy involved in the TNFalpha-mediated state-dependent enhancement of EEG slow wave activity.