Development-Related Expression of AKAP79 in the Striatal Compartments of the Human Brain

Abstract

The expression of AKAP79 which tethers regulatory proteins within postsynaptic densities has been studied in the two striatal compartments, i.e. patches and matrix, at different stages of the developing human brain by means of immunohistochemistry. The two striatal compartments exhibit various intensities of diffuse immunolabelling and a different number of immunoreactive nerve cells. From the 14th to 20th gestational week a nearly homogeneous distribution of immunoreactive structures in the two compartments of the striatum is seen. Thereafter, a decrease in immunoreactive structures within the matrix is observed (22nd–25th week, intermediate stage). From the 27th week onwards the patch compartment contains distinctly more immunoreactive puncta and nerve cells. Thus, the patches stand out clearly in the immunopreparations. This distribution pattern does not change during proceeding development. AKAP79-immunoreactive nerve cells closely resemble those constituting the class of medium-sized inhibitory projection neurons that receive the dopaminergic input of the striatum. Literature data suggest that AKAP79 may be functionally attributed to dopaminergic inputs. Accordingly, the patterns of AKAP79 expression can at least in part be correlated with the sequential occurrence of dopaminergic innervation. The mature matrix containing a dopaminergic innervation being as dense as in the patches displays distinctly less AKAP79-immunoreactive neurons and puncta than the patches. This discrepancy might indicate that a subpopulation of matrix neurons may, despite dopaminergic input, not express AKAP79.

A Potential Role for a Genetic Variation of AKAP5 in Human Aggression and Anger Control

“…A similar expression pattern was observed in the medial OFC (BA 11). To verify the validity of these findings, AKAP5 immunoreactivity was also assessed in the hippocampus and striatum, brain regions that have previously been shown to express AKAP5 (Sik et al, 2000; Ulfig et al, 2001; Figure 4A, bottom row). Western blotting using the same primary antibody revealed expression of the previously observed AKAP5-immunoreactive band at approximately 75 kDa (Gardner et al, 2006) in the detergent-insoluble pellet fractions of the human hippocampus and cingulate cortex (Figure 4B), but not in the cerebellum, compatible with previous observations for the AKAP5 ortholog in rodents (Ostroveanu et al, 2007), thus confirming the specificity of the antibody.…”

“…Protein structure prediction suggests that this amino acid substitution might influence protein folding and curvature (Figure 1B) Based on cell-biological findings and animal experiments about AKAP function as a key synchronizer of neuronal events (Tunquist et al, 2008) and its association with GPCR signaling, we therefore hypothesized that the polymorphism might influence human aggression as well as aggression-related emotions and their control. Previous expression studies of the human AKAP5 gene product (AKAP79) showed a high abundance in several CNS regions relevant for emotional and motivational processes, including the amygdala, the hippocampus and the striatum (Sik et al, 2000; Ulfig et al, 2001, 2003), also pointing to a role of AKAP5 in human emotional processing.…”

The non-human primate striatum undergoes marked prolonged remodeling during postnatal development

“…The ontogeny of the human striatum has not been studied comprehensively, and, indeed, very few studies have been done. Most studies to date have focused on the fetal brain (13–40 weeks gestation) and have shown in striatum patchy distributions with striosomal enrichments of acetylcholinesterase (AChE) and muscarinic cholinergic binding sites (Nastuk and Graybiel, 1985), AChE and NADPH-diaphorase (Sajin et al, 1992), calbindin (Letinic and Kostovic, 1996), dopamine D1 receptor and dynorphin mRNA (Brana et al, 1996), glutamate receptor scaffold kinase anchoring protein (Ulfig et al, 2001), and synaptophysin (Ulfig et al, 2000). A study of postnatal human brain revealed an inversion from an immature pattern of calbindin-enriched striosomes to a mature pattern of calbindin-enriched matrix sometime between term gestation to 18 months of life (Letinic and Kostovic, 1996).…”

Effects of AKAP5 Pro100Leu Genotype on Working Memory for Emotional Stimuli

“…AKAP5 is expressed throughout the human brain, including the amygdala, the hippocampus, and the striatum as well as distributed cortical regions like the anterior cingulate and the dorsolateral prefrontal and orbitofrontal cortices [38], [44], [78], [79]. While copy number variations of the AKAP5 gene have been implicated in the risk for schizophrenia and bipolar disorder [80], the Pro100Leu polymorphism has thus far not been associated with risk for major psychiatric disorders.…”