Decreased numerical density of kainate receptor-positive neurons in the orbitofrontal cortex of chronic schizophrenics.

We utilised postmortem brain tissue to quantify sections of left and right orbitofrontal cortex (area 11) from nine schizophrenic and eight control patients from the Charing Cross Prospective Schizophrenia Study immunostained for the presence of the kainate receptor (GluR5/6/7). The numerical density of neurons immunopositive for kainate receptor was measured. Other sections from the same blocks were stained with cresyl violet to determine the total neuronal numerical density. All measurements were made blind: diagnoses were only revealed by a third party after measurements were completed. There was a significant reduction (21%) in numerical density of kainate receptor-positive neurons in both cortices in the schizophrenic group (488 cells/mm2) compared to that in the control group (618 cells/mm2) (P=0.033). Nissl-stained tissue showed no significant difference in total neuronal numerical density between control and schizophrenic groups. These observations suggest that there are actually fewer kainate receptor-positive neurons in schizophrenic orbitofrontal cortex. There was no correlation of reduced kainate receptor-positive cell number with age at death, postmortem interval, or other possibly confounding neuropathology. Our results support the concept of there being reduced glutamatergic activity in frontal cortex in schizophrenia.

Laser photocoagulation alters the pattern of staining for neurotrophin-4, GFAP, and CD68 in human retina.

AIMS: To investigate the staining pattern of neurotrophin-3 (NT3), neurotrophin-4 (NT4), and brain derived neurotrophic factor (BDNF) as well as glial fibrillary acid protein (GFAP) and CD68 in lasered human retina. METHODS: Retinal laser photocoagulation was performed on four patients (two males, two females) with choroidal malignant melanoma 1-6 days before enucleation. Three other enucleated eyes with malignant melanoma and three normal cadaveric donor eyes were used as controls. Immunohistochemistry was performed to investigate the pattern of staining of NT3, NT4, BDNF, GFAP, and CD68 in 7 mm sections of fixed specimens. RESULTS: Expression of NT4 was detected in the inner and outer nuclear layers of all the retinal sections examined but no NT3 and BDNF staining was seen. NT4 staining was found to be less intense in lasered and melanoma controls compared to normal cadaveric donor retinas. There was an upregulation of GFAP expression in both lasered and control eyes with melanoma in comparison with normal controls. CD68 staining was only observed in retinal pigment epithelium and choroid of lasered eyes. CONCLUSION: NT4 is expressed in inner and outer nuclear layers of normal human retina and its expression is downregulated following laser photocoagulation. This occurs in parallel with an increased expression of GFAP suggesting that reactive changes in Muller cells may be responsible for reduced NT4 staining. Expression of CD68 at the site of laser injury is consistent with a wound healing process as a response to local damage.

Increased expression of NADPH-diaphorase in visual centres after unilateral optic nerve transection in the rat.

The present study shows an increase NADPH-d histochemical staining in the optic layers of the superior colliculus, the ventral nucleus of the lateral geniculate body and the primary visual cortex in the rat after transection of the contralateral optic nerve. The alteration was observed 4-60 days after the lesion, with a maximum at 30 days. These results suggest that retinal activity has a transneuronal and time-dependent regulatory effect on nitric oxide synthesis in denervated or visually deprived visual centres, an increase that may play a role in enhancing local blood flow and could be neuroprotective in function.

Protein gene product 9.5-immunoreactive retinal neurons in normal developing rats and rats with optic nerve or tract lesion.

The present immunocytochemical study indicates that protein gene product 9.5 (PGP 9.5) in the rat retina first appears in a population of neurons in the inner and central part of the neuroblast layer at embryonic day (E) 14. Presumptive horizontal cells which are PGP 9.5 positive were observed at E17. At birth, cells in the inner nuclear layer and ganglion cell layer (GCL) as well as the inner plexiform layer (IPL) were positive. Further differentiation, particularly the appearance and the formation of immunoreactive sublaminae in the IPL, was observed in the first 2 postnatal weeks. This pattern reached adult levels by postnatal day 14. In rats with unilateral neonatal optic tract lesion or optic nerve transection as young adults, 43-45% of the immunoreactive cells were lost in the GCL. However, only minor changes were detected in the IPL, suggesting that amacrine cells contribute mainly to the PGP 9.5 immunoreactivity in this laminar zone of the retina.

Injury-resistant retinal ganglion cells that are rich in cytochrome oxidase.

Previous studies have demonstrated that the vast majority of retinal ganglion cells (RGCs) die one month after optic nerve transection. However, a small percentage do not degenerate. The present study examined one aspect of the chemical nature of these surviving RGCs using cytochrome oxidase (CO) as a neuronal marker in whole-mounted retinae. In the normal retina, 4.3% of the total population of RGCs show high CO activity. One month after optic nerve transection, 37% of the CO-positive RGCs counted in the control retinae survive and, because they stain with CO, must be metabolically active. Previous studies have shown that only up to 10% of the total RGC population survive optic nerve transection. The implication of our results is that the CO-positive RGCs, as a subpopulation, are more resistant to injury than the general population of RGCs.