Stephen A. Berman

Cell proliferation in the brains of NMDAR NR1 transgenic mice.

We have used genetically engineered NMDA receptor NR1+/- mice in which the gene for the NR1 subunit was modified in such a way that these mice express only 50% of the NR1 subunit. The NR1 subunit is necessary for NMDA receptor channel function. We investigated the effects of reduced NMDA receptor function on cell proliferation in the hippocampus and the amygdala of the adult mouse brain. Transgenic (NR1+/-) and wild-type (NR1+/+) mice were injected with BrdU. We collected brain sections cutting through the rostro-caudal extension of the entire hippocampus of the NR1+/- and NR1+/+ (wild-type) mice. The phenotype of BrdU-positive cells was identified by double labeling with antibodies to neuronal or glial markers. Our results show that the NR1+/- mice, which express the NMDAR NR1 subunit at a low level, have a significant (p<0.01) increase in the number of BrdU-positive cells in the dentate gyrus and the amygdala compared to NR1+/+ mice. Some of these dividing cells express the neuronal marker NeuN. Our results indicate that low expression of the NR1 subunit significantly increases cell proliferation and neurogenesis, suggesting that low NMDARs activity contributes to the increase in cell proliferation in the adult brain.

Differential responses of human neuroblastoma and glioblastoma to apoptosis.

Staurosporine, a protein kinase and etoposide, a topoisomerase II inhibitor, are known to enhance apoptosis. The differential effects of these agents on T98G glioblastoma and SK-N-SH neuroblastoma, cell lines both derived from human tumors, have not been determined. We assessed cellular viability, DNA fragmentation and laddering, chromatin condensation, and Poly(ADP-ribose) polymerase (PARP) cleavage induced by these agents at a series of concentrations and times. In addition, to gain an understanding of the mechanism by which these agents work, we measured Protein Kinase C (PKC) activity. Staurosporine induced significant alterations in all apoptotic parameters tested in both cell lines. Etoposide induced apoptotic alterations similar to those caused by staurosporine in neuroblastoma but produced no detectable apoptotic changes in glioblastoma cells. Etoposide induced membrane but not cytosolic PKC activity in neuroblastoma but had no effect on PKC activity in glioblastoma. Our results show that the induction of apoptosis is cell type dependent. PKC activity appears to be crucial in the initiation of apoptosis.

Pathological left-handedness and preserved function associated with a slowly evolving brain tumor.

The authors report the serial neuropsychological evaluations of a patient, with acquired left‐handedness who had a massive brain tumor that infiltrated the entire temporal and posterior parietal lobes of the left hemisphere. Although the patient had pre‐operative impairment of non‐verbal memory, follow‐up assessment 31 and 66 months after the tumor was resected revealed cognitive functions to be in the high‐average to superior range. This case demonstrates the sparing of neuropsychological functions that can be seen with a slowly evolving lesion. The authors suggest that such functional sparing may be due to transfer of function rather than to the residual function of tumor‐infiltrated neuronal tissue. Possible mediators of functional preservation include slow lesion growth, the patients youth at disease onset and the large size of the lesion.