Ageing of substantia nigra in humans: cell loss may be compensated by hypertrophy.

In a stereological study of the human substantia nigra (SN), the total number of melanin-positive and melanin-negative neurones from 28 male subjects aged 19-92 years was estimated using a uniform sampling design and optical disectors. There was a significant decrease in the total number of melanin-positive neurones as a function of age (r(2)=0.18, residual-CV=0.35, 2P=0.032). Using the rotator method, the size distribution of the melanin-positive neurones was estimated and showed a significant difference in mean cell volume of melanin-positive neurones between the seven youngest (21,077 microm(3)) and the seven oldest individuals (32,011 microm(3)), 2P=0.022. Using a combination of the total number of melanin-positive neurones and their size distribution, the total perikaryon volume of melanin-positive neurones could be estimated and showed no decrease with increasing age (r(2)=0.01, residual-CV=0.41, 2P=0.62). Age-related decline in dopamine-transporter neurones within the SN might explain the occurrence of extrapyramidal symptoms in many elderly individuals. Although age-related cell hypertrophy is usually considered to be an indication of cell degeneration or necrosis, this might not always be the case. The fact that motor symptoms, although present in many of the elderly, are of a limited nature despite the high percentage of lost neurones could be due to a compensatory increase in the cell body of dopamine-producing SN neurones. Thus, the total amount of cell substance capable of producing the essential transmitters might not be reduced to a critically low level as a result of ageing.

No deficit in total number of neurons in the prefrontal cortex in schizophrenics.

The prefrontal cortex (PFC), defined as the cortical region which has the major reciprocal connections with the mediodorsal thalamic nucleus (MD), has often been implicated in schizophrenia. Morphometric studies have shown altered neuronal density and structure in parts of the PFC in schizophrenic brains. In addition, the MD and nucleus accumbens have shown a significant deficit in total neuron number. The purpose of the present study was to estimate the total neuron number in the PFC in schizophrenics and controls. Using a stereological design, the PFC was studied in eight brains from schizophrenic patients and 10 age-matched control brains. The bilateral average total number of neurons in the PFC was estimated to be 2.76 x 10(9) (CV=S.D./mean=0.15) in the schizophrenic brains whereas that of controls was a non-significantly different value of 3.11 x 10(9) (CV=0.22; P=0.23). Furthermore, no significant differences were found between the two groups in neuronal density (P=0.10) or volume of the PFC (P=0.49). It is of course possible that a neuronal deficit, which cannot be revealed when estimating the total global number of neurons in the whole PFC, might exist in a subregion of the PFC. In conclusion, uniform loss of neuronal soma in the PFC does not appear to constitute the neural substrate of the pathological process in schizophrenia.

Stereological studies of the schizophrenic brain.

Stereological studies have contributed with important results to the understanding of brain abnormalities in schizophrenia. The data obtained from stereological studies of brains from schizophrenic patients, including studies of the thalamus, hippocampus, and cortex, are discussed and suggest a central role of the thalamic nuclei in the etiology of the disease. The basic stereological tools are presented and possible biases in quantification studies are discussed.