L.J. Garey

A Pivotal Role for Glutamate in the Pathogenesis of Schizophrenia, and Its Cognitive Dysfunction

There is mounting evidence of a glutamate dysfunction in schizophrenia, as suggested by the fact that schizophrenia and phencyclidine psychosis are similar and phencyclidine is known to block the N-methyl-D-aspartate (NMDA) subtypes of glutamate. Both occur mainly after puberty, suggesting they may share similar underlying developmental processes. Direct evidence is now accumulating from the study of messenger RNA that glutamate receptor deficiencies occur in schizophrenia and are regionally and specifically distributed. These results find support from studies of memory, electrophysiological findings, clinical treatment, and pharmacological studies in mammals and humans. Our recent findings of: a) a marked decrease in pyramidal cell dendritic spines in layer III of the frontal and temporal cortex, and b) a greater than 0.90 correlation between decrease in mRNA for the NMDA glutamate receptor and cognitive deterioration in elderly schizophrenics, present the strongest evidence to date that glutamate dysfunction plays an important role in schizophrenia.

Bcl-2 proto-oncogene protein immunoreactivity in normally developing and axotomised rat retinas

This study demonstrates immunocytochemically that bcl-2 (B cell lymphoma) proto-oncogene protein is expressed by two populations of retinal cells, one in the inner retina representing developing neurons or glia at perinatal stages, and the other identified as Müller cells from postnatal day 10 onward. An increase in bcl-2 immunoreactivity was detected in the Müller cell processes after neonatal optic tract lesion or optic nerve transection in adult rats. These results suggest that bcl-2 protein may function on cellular differentiation, maturation and homeostasis in the inner retina, and its expression by Müller cells can be up-regulated by the degeneration of ganglion cells.

Distribution of β-amyloid Precursor and B-cell Lymphoma Protooncogene Proteins in the Rat Retina after Optic Nerve Transection or Vascular Lesion

The expression of beta-amyloid precursor protein (APP) and B-cell lymphoma protooncogene protein (Bcl-2) in retinal cells in the rat was studied using immunocytochemistry at different times after intraorbital optic nerve transection or vascular lesion. Three hours to one month after transection of the optic nerve, a significant increase in APP and Bcl-2 immunostaining was observed in retinal Müller glia but not in retinal neurons. In contrast, injury to blood vessels that supply the eye without cutting the optic nerve resulted in a complete loss of APP and Bcl-2 immunostaining in Müller cells and an increase in immunoreactivity in distinct populations of retinal neurons. The overall pattern of APP immunostaining in Müller cells and neurons was essentially the same as that of Bcl-2 under identical experimental conditions. These results suggest that the expression of APP and Bcl-2 in retinal cells is dependent on the nature and severity of injury, and that rapid and common mechanisms are involved in regulating the expression of these molecules.

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.