AG230 Sigma-AldrichGlial Fibrillary Acidic Protein, porcine

There is much controversy regarding the extent of axon regeneration/sprouting ability in adult human brain. However, intrinsic differences in axon/neurite growth capability amongst striatal (caudate, putamen, nucleus accumbens) subdivisions could conceivably underlie, in part, their differential vulnerability in degenerative human brain disorders. To establish whether the distribution of axon growth markers in mature human striatum might be uniform or heterogeneous, we measured the intra-striatal pattern, in autopsied brain of normal subjects (n=40, age 18-99), of proteins involved in regulating axon growth. These proteins included polysialylated neural cell adhesion molecule (PSA-NCAM), microtubule-associated proteins TUC-4 (TOAD/Ulip/CRAMP-4) and doublecortin (DCX), and Bcl-2. The distribution of the marker proteins within the striatum was heterogeneous and inversely related to the pattern of dopamine loss previously characterized in Parkinson's disease (PD), with levels in nucleus accumbensgreater than caudategreater than putamen, ventralgreater than dorsal, and rostral putamengreater than caudal. In contrast, distribution of glial markers including glial fibrillary acidic protein (GFAP) and human leukocyte antigens (HLA-DRα and HLA-DR/DQ/DPβ), other Bcl-2 family proteins, and control proteins neuron-specific enolase and α-tubulin in the striatum was either homogeneous or had a pattern unmatched to dopamine loss in PD. The putamen also showed more marked age-dependent decreases in concentrations of PSA-NCAM, TUC-4, and DCX and increases in GFAP levels than caudate. We conclude that the intrastriatal pattern of several key axon growth proteins is heterogeneous in adult human brain. Further investigation will be required to establish whether this pattern, which was inversely correlated with the pattern of dopamine loss in PD, is involved to any extent in the pathophysiology of this degenerative disorder.

For many temperate-zone avian species, termination of breeding occurs when individuals no longer respond to previously stimulatory day lengths, a condition called photorefractoriness. Long day lengths induce significantly greater expression of c-fos and fos-related antigens (FRAs) in the tuberal hypothalamus of the photosensitive hen than that of the photorefractory hen. The tuber is also a site of photoinducible glial expression of type 2 iodothyronine deiodinase (Dio2), which converts thyroxine into its active form, triiodothyronine (T3). T3 induces withdrawal of glial processes from gonadotrophin-releasing hormone (GnRH) I nerve terminals, which is believed to permit the efficient release of GnRH I into the associated portal vasculature. Using a riboprobe, we tested whether long days induce Dio2 mRNA expression in the turkey tuber and, if so, whether this expression is reduced in photorefractory hens. Long days significantly induced rostral and caudal tuberal hypothalamic Dio2 expression in photosensitive hens. Photorefractory hens had reduced expression of Dio2 with most subjects expressing no detectable mRNA in the rostral tuber and variably attenuated amounts throughout the medial and caudal tuber. We also performed double-label immunohistochemistry to identify co-localisation between FRAs and glial fibrillary acidic protein, a glial marker. FRAs were present in the nuclei of a few astrocytes in the median eminence and infundibular nucleus of the tuber. The temporal and spatial coincidence between FRA and Dio2 expression, their mutual association with glia, and the attenuation of their response during photorefractoriness suggests that the two events are linked and that photorefractoriness involves a reduced capacity for photo-inducible gene expression within glia of the tuberal hypothalamus.