Jytte Overgaard Larsen

Selective degeneration of dorsal root ganglia and dorsal nerve roots in methyl mercury-intoxicated rats: a stereological study

Abstract The components of the nervous system of rats that are most critically affected by methyl mercury are still a matter of debate. A recent stereological study of rats with typical symptoms resulting from methyl mercury intoxication demonstrated that the morphology of cerebellar granule cells and Purkinje cells were unchanged at the light microscopic level, even though there was pronounced degeneration of myelinated axons in dorsal nerve root nerves. In the present study, unbiased stereological methods were used to quantify morphological changes in the dorsal root ganglion, and dorsal and ventral nerve roots of the rats used in the previous study. The rats were treated with methyl mercury (2 mg daily/kg, per os) for a 19-day period that was followed by a 32-day period without treatment. The means of the total numbers of A-cell and B-cell perikarya in the dorsal root ganglion of the intoxicated rats were reduced by 60% and 24%, respectively. The mean volume of A-cell perikarya in rats of the experimental group was reduced by 22%, whereas the mean volume of B-cell perikarya was the same in the two groups. In the experimental group, the total number of myelinated axons in the dorsal nerve roots was reduced by 60%, whereas no difference was found in the ventral nerve roots. The areas of axon and myelin sheath, dorsal and ventral nerve roots were not affected. This study demonstrates that extensive loss of dorsal root ganglion cells and myelinated axons in dorsal nerve roots precedes light microscopical changes in the ventral nerve roots and the cerebellum of rats intoxicated with methyl mercury.

Neuron loss in cerebellar cortex of rats exposed to mercury vapor: a stereological study

Abstract Mercury vapor produces tremor in humans and experimental animals. We have previously reported that mercury vapor intoxication over an 8-week period induces only subtle changes in dorsal root ganglia and nerve roots in rats. In the present study we have carried out stereological analyses of the cerebellum of the same rats, and demonstrated significant losses of Purkinje cells (12.7%, 2P = 0.005) and granule cells (15.6%, 2P = 0.016). All sizes of Purkinje cells were lost with an equal probability, i.e. there were no indication of any preferential loss of any subpopulation of the neurons. The volume of the granular cell layer was significantly reduced (18.9%, 2P = 0.015), whereas the volumes of the molecular layer and the white matter were unchanged. Previous stereological studies have demonstrated that methyl mercury intoxication primarily induces degeneration in the peripheral nervous system, while sparing the cerebellum. We therefore suggest that metallic mercury vapor and methyl mercury have different toxicological profiles in rats, where metallic mercury vapor mainly affects the central nervous system and methyl mercury mainly affects the peripheral nervous system.

A stereological study of dorsal root ganglion cells and nerve root fibers from rats exposed to mercury vapor

Abstract Although mercury vapor is known to produce tremor and peripheral neuropathy, neuropathological studies of the effects of the vapor are few in number. The aim of the present study has been to evaluate the effect of mercury vapor on the morphology of the dorsal root ganglion and the spinal nerve roots. Adult male rats were exposed to mercury vapor for 33 days. The exposed rats developed somatic signs of intoxication and became increasingly irritable. The total numbers and volumes of A- and B-cell perikarya in the dorsal root ganglia, the total number of myelinated axons in the roots, and the cross-sectional areas of axon and myelin in the nerve roots were estimated using unbiased stereological principles. The mean cross-sectional area of myelin associated with nerve fibers in dorsal nerve roots of the exposed group was significantly reduced by 20% (2P = 0.014). A tendency towards a reduction was seen in axon area of myelinated nerve fibers in the dorsal nerve roots (2P = 0.087) and in the total numbers and mean volume of A-cell perikarya (2P = 0.059 and 2P = 0.087, respectively). No differences between the two test groups were found for any of the parameters measured in B-cells and ventral nerve roots. It is concluded that mercury vapor, in a dose sufficient to produce intoxication, induces only minor changes in dorsal root ganglion and nerve roots in rats.

A stereological study of dorsal root ganglion cells and nerve root fibers from rats treated with inorganic mercury

Abstract Unbiased stereological methods have been used to quantify the effects of inorganic mercury on the morphology of the fifth lumbar dorsal root ganglion cells and nerve root fibers. Adult male Wistar rats were treated with intraperitoneal injections of mercuric chloride (0.15 mg daily) for 30 days. The total numbers and mean volumes of A- and B-cell perikarya were estimated using the optical fractionator and the vertical rotator techniques. The total numbers of myelinated axons in the ventral and the dorsal roots were estimated with the two-dimensional fractionator technique and the areas of axon and myelin were estimated using the two-dimensional nucleator technique. No differences were found for any parameters in experimental and control animals, indicating that inorganic mercury intoxication alters neither the numbers or sizes of dorsal root ganglion cells and nerve root fibers nor the amount of myelin associated with the nerve fibers.

Effect of chronic lithium treatment with or without haloperidol on number and sizes of neurons in rat neocortex

The present study used stereological methods to determine whether long-term administration of lithium, with or without haloperidol, affects the number and average volume of neocortical neurons. Twenty-five rats were divided into three groups and given no treatment, lithium, or lithium combined with haloperidol. Serum lithium levels ranged from 0.5 to 0.8 mmol/l. Haloperidol was injected intraperitoneally at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the brains were prepared. Neocortical volume, density of neurons, total number of neurons and mean volume of neurons were estimated. As no differences were found between the groups, the present study provides no evidence for quantitative morphological changes in the cerebral cortex due to long-term ‘therapeutic’ levels of lithium, with or without haloperidol.

The volume of Purkinje cells decreases in the cerebellum of acrylamide — intoxicated rats, but no cells are lost

The effects of acrylamide intoxication on the numbers of granule and Purkinje cells and the volume of Purkinje cell perikarya have been evaluated with stereological methods. The analysis was carried out in the cerebella of rats that had received a dose of 33.3 mg/kg acrylamide, twice a week, for 7.5 weeks. The total numbers of cerebellar granule and Purkinje cells were estimated using the optical fractionator and the mean volume of the Purkinje cell perikarya was estimated with the vertical rotator technique. The volumes of the molecular layer, the granular cell layer and the white matter were estimated using the Cavalierí principle. The mean weight of the cerebellum of the intoxicated rats was 7% lower than that of the controls rats (2P=0.001). The numbers of the Purkinje cells and granule cells were the same in both groups, but the mean volume of the perikarya of the Purkinje cells in the intoxicated rats was 10.5% less than that of the control group (2P=0.004). The volume of the granular cell layer was reduced by 15% (2P=0.006) but there were no differences in the volumes of the molecular layer and the white matter in the intoxicated and control animals.

Structural preservation of cerebellar granule cells following neurointoxication with methyl mercury: a stereological study of the rat cerebellum

Methyl mercury intoxication causes ataxia. Structural changes of cerebellar and peripheral nerve tissues have been described. However, it is still unclear whether the ataxia is of cerebellar or peripheral origin. To clarify this question further, the effects of methyl mercury intoxication on the numbers of granule and Purkinje cells and the volume of Purkinje cell perikarya have been evaluated with stereological methods. Rats were intoxicated with methyl mercury, at a dose of 2 mg/kg per day for 19 successive days, and the analysis was carried out 2.5 or 4.5 weeks later. The total numbers of cerebellar granule cells and Purkinje cells were estimated using an optical fractionator and the mean volume of the Purkinje cells was estimated by the vertical rotator technique. The volumes of the granular cell layer, the molecular layer and the white matter were estimated using the Cavalieri principle. The intoxicated animals developed hindlimb incoordination when held by the tail. Although pronounced axonal degeneration occurred in the peripheral nervous system, no changes were found in cerebellar cell numbers or cell sizes in either of the test groups. The absence of detectable light microscopic changes in the cerebellum indicates that the peripheral nervous system is affected prior to the cerebellum in rats intoxicated with organic mercury.

Chronic lithium treatment with or without haloperidol fails to affect the morphology of the rat cerebellum

We used unbiased stereological principles to determine whether long-term administration of lithium at human therapeutic levels, with or without haloperidol, affects the number or sizes of cerebellar Purkinje cells or the volume of histological layers in the rat cerebellum. Twenty-eight rats were randomly divided into three groups, receiving either no treatment, lithium, or lithium combined with haloperidol. The serum lithium levels ranged from 0.50 to 0.77 mmol/l. Haloperidol was given at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the cerebelli were histologically prepared. No statistically significant differences were observed between the groups with respect to the cerebellar measures.