**3.3 IGF receptor expression in the brain**

IGF-1R mRNA is widely expressed in the developing CNS and persists at high levels in the mature brain especially in neuron-rich regions such as the olfactory bulb, the granule cell layer of the dentate gyrus and cerebellar cortex (Rotwein et al. 1988; Bondy et al. 1990; Bondy and Lee 1993; Werther et al. 1990). Glia cells have a lower IGF-1R expression than neurons and therefore regions mainly containing those cells, like white matter zones, show low IGF-1R mRNA levels (Bondy and Lee 1993). Some neurons, which are still in the process of developing, express increasing IGF-1R mRNA levels postnatal until they have reached maturity, for example Purkinje cells (Bondy et al. 1992). In the adult brain, high expression levels of IGF-1R mRNA are also found in the choroid plexus, meninges and vascular sheaths (Bondy et al. 1992; Bohannon et al. 1988; Werther et al. 1989; Matsuo et al. 1989; Marks, Porte, and Baskin 1991).

The IGF-2R is abundantly expressed in the CNS, especially in the pyramidal cell layers of the hippocampus, the granule cell layer of the dentate gyrus, olfactory bulbus, choroid plexus as well as in the microvasculature, retina, pituitary, brainstem and spinal cord (Hawkes and Kar 2004; Couce, Weatherington, and McGinty 1992; Wilczak et al. 2000; Valentino, Ocrant, and Rosenfeld 1990).

In addition to the IGF-1R and the IGF-2R, IR and IGF-1R hybrids are expressed in the brain, through which IGFs and insulin induce intracellular signalling. IRs are mainly expressed in regions that are linked to olfaction, appetite and autonomic functions, such as the olfactory bulb, limbic system and hypothalamus (Werther et al. 1987; Unger, Livingston, and Moss 1991) and seem to play a key-role in controlling feeding, body weight and reproduction (Bruning et al. 2000). Furthermore, IR expression is also present in remarkable concentration in the choroid plexus, circumventricular organs and brain microvessels (van Houten and Posner 1979, 1981; Werther et al. 1987) suggesting the IRs might contribute to the transport of insulin and possibly IGF-1 across the BBB.
