Accumulating evidence suggests that changes in dietary folate intake may modulate the risks of Alzheimer's disease (AD) through as yet unknown mechanisms. The aims of the present study were to investigate how dietary folate affects the brain folate distribution, levels of oxidised lipid and DNA damage in the absence/presence of β-amyloid(25–35) (Aβ) peptide challenge, a pathogenic hallmark of AD. Male Wistar rats were assigned to diets with folic acid at 0 (folate deprivation; FD), 8 (moderate folate; MF) and 8 mg folic acid/kg diet+0·003 % in drinking-water (folate supplementation; FS) for 4 weeks. A single injection of Aβ peptide (1 mg/ml) or the vehicle solution was intracerebroventricularly (icv) administrated to rats a week before killing. Brain folate, a marker of oxidative injury, and neuronal death were assayed. In the absence of an Aβ injection, FD rats showed reduced folate levels, and increased 2-thiobarbituric acid-reactive substances and a mitochondrial (mt)DNA 4834 bp large deletion (mtDNA4834 deletion) in the hippocampus compared with the counterpart brains of control rats (P < 0·05). A single icv injection of Aβ peptide potentiated lipid peroxidation in the medulla of FD rats, which was ameliorated by feeding FD rats with the MF and FS diets (P < 0·05). Feeding the FS diet to Aβ-injected rats enriched brain folate levels and reduced mtDNA4834 deletion in the hippocampal and medullary regions compared with corresponding tissues of Aβ+FD rats (P < 0·05). Aβ+FS rats had reduced rates of neuronal death in the frontal cortex compared with Aβ+FD rats (P < 0·05). Taken together, our data revealed that folate deprivation differentially depleted brain folate levels, and increased lipid peroxidation and mtDNA4834 deletions, particularly, in the hippocampus. Upon Aβ challenge, the FS diet may protect various brain regions against lipid peroxidation, mitochondrial genotoxicity and neural death associated with folate deprivation.

We have examined the effects of neonatal monocular enucleation on the volume of the dorsal lateral geniculate nucleus (dLGN), the area of area 17, and the size and numbers of geniculate relay neurons identified by retrograde transport of HRP from cortex. Compared to values for normal animals, the only significant change contralateral to the remaining eye was an increase in relay cell radius. The effects ipsilateral to the remaining eye were more widespread: we found significant reductions in the volume of the dLGN (27% reduction), the area of striate cortex (22%), and the number (16%) and average soma radius (6%) of geniculate relay neurons. The relay neurons were also more densely packed, suggesting that other geniculate cell types were affected similarly, although this was not explicitly examined. These changes were not uniform throughout the nucleus, and as such, reflected the changes in retinal input. The greatest reduction in cell size occurred in the region of the ipsilateral dLGN receiving the most sparse retinal input subsequent to enucleation. Nor was the shrinkage of the dLGN uniform, being most apparent in the coronal plane especially along the axis orthogonal to the pia; there appeared to be little change in the anteroposterior extent. Shrinkage in area 17 ipsilateral to the remaining eye was the same (about 22%) whether it was defined by myelin staining or transneuronal transport of WGA-HRP. These results show that the transneuronal changes seen in the organization of visual cortex after early monocular enucleation in rodents are associated with only a moderate loss of geniculate relay cells.

As a major morphological feature in establishing the form of the nervous system, it is recognized that neurons are initially overproduced, then naturally occurring cell death reduces the neuron number to the functional requirement. However, the mechanisms controlling the selective elimination of certain neurons during a general phase of cell death are not fully understood. One event that seems to be pivotal is the establishment of neural connections, the degree of which may be influential regarding the fate of specific neurons. However, little quantitative evidence is available to either support or refute this theory. In this current study, a Stereological measurement of gap junction per neuron was carried out within the invertebrate model system of the tapeworm metacestode Mesocestoides corti, which has previously been shown to overproduce neurons during the asexual reproduction stage of its life-cycle. Novel Stereological estimation methods with ‘ vertical sections’ indicated that prior to asexual division the cerebral ganglion possessed approximately 268 neurons, each with a gap junction surface area of 250 μm2. As division progressed, the neuron number increased to approximately 700, while the total surface area of gap junction remained statistically unchanged. As a result the surface area of gap junction per neuron decreased to 106 μm2, less than half that in the undividing stage. These results provide the first non-biased quantitative data regarding changes in the mean surface area of gap junction per neuron in a developing cerebral ganglion.