Immunohistochemical studies on the distribution of microcirculation-controlling factors in the cerebral cortex and hippocampal formation of the aged rat / 대한해부학회지

Recent studies have explored certain changes of neurons containing neuropeptides that are involved in the cerebral microcirculation with aging. However, the degree of loss of vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-containing neurons in the aged CNS has not yet been established with certainty. Nitric oxide (NO) from the neuronal NO synthase (nNOS) appears to play the principal role in the cerebral flow response to functional activation. Several findings suggest that NO production may be decreased in the aged rat. Therefore, changes with aging of VIP-, NPY- and NOS-containing neurons were demonstrated by immunohistochemistry in this study. A major loss of VIP-immunoreactive (IR) neurons in the aged rat brain was observed in the frontal cortex area 3, parietal cortex area 1, hindlimb area, temporal cortex area 1 & 2, monocular part of occipital cortex area 1, occipital cortex area 2, and retrosplenial cortex. The axis of VIP neurons in the aged group showed an irregular orientation tendency, especially in layers II and III. Major loss of NPY-IR neurons in the aged rat brain were observed in the retrosplenial cortex, frontal cortex areas 1 and 2, parietal cortex areas 1 and 2, occipital cortex areas 1 and 2, the temporal cortex, hippocampus proper and cingulate cortex. Loss of NPY-IR neurons was observed mostly in layers V and VI. The number of NOS-IR cells was significantly decreased in the aged rat, but the extent of changes was variable in each area.Morphologically, the number of dendritic branches seemed to be decreased in the aged group and the length of dendrites of VIP-, NPY- and NOS-IR neurons showed a tendency to shorten. These results indicate the involvement of VIP-, NPY- and NOS-IR neurons in the aging process in relation to the increased incidence to cerebrovascular disorders in the elderly, and provide the first morphological evidence for the loss of VIP-, NPY- and NOS-IR neurons in each area of cerebral cortex and the hippocampus of the aged rat by immunohistochemistry.

Immunocytochemical study on the distribution of NOS-immunoreactive neurons in the cerebral cortex of aged rats / 대한해부학회지

Nitric oxide (NO) involvement has been demonstrated in mechanisms of synaptic plasticity, particularly in hippocampal long-term potentiation, a mechanism that underlies certain forms of learning and memory. Further, NO has been shown to regulate various neurotransmitters which play an important role in learning and memory. Several findings suggest that NO production may be decreased in the aged rat. Changes in the nNOS-containing neurons with aging were demonstrated by immunocytochemistry and in situ hybridization. NOS-immunoreactive cells in aged rats were present in all cortical areas and the hippocampus, and the pattern of distribution was similar to that of the control group. The number of NOS-immunoreactive cells in the cerebral cortex was significantly decreased in the aged rats, but the extent of changes was variable in each area, and ranged from mild decrease (50%). Severely decreased areas were the cingulate cortex, parietal cortex area 1, temporal cortex area 1, 2, 3, medial part of occipital cortex area 2, monocular and binocular part of occipital cortex area 1, entorhinal cortex, hippocampus proper, dentate gyrus and subiculum. Moderately decreased areas (30~50%) were frontal cortex area 1, 2, 3, parietal cortex area 2, forelimb, hindlimb, lateral part of occipital cortex area 2. Slightly decreased area was insular cortex. Morphologically, the number of dendritic branches seemed to be decreased in aged group and the length of dendrites of NOS-IR neurons showed a tendency to shorten. These results indicate the involvement of neuronal system containing NOS in the aging brain, and provide the first morphological evidence for the loss of NOS neurons in the cerebral cortex of the aged rats by immunocytochemistry. Further multidisciplinary investigations involving normal aging and neurodegenerative disease such as Alzheimer's disease are needed to clarify the importance of nitric oxide changes in the cerebral cortex with aging.

Spatial and temporal expression patterns of apoptosis-related genes in rat spinal cord during normal aging / 대한해부학회지

The pattern of distribution in rat spinal cord and changing pattern during normal aging of c-Fos, Bcl-2, Bax, and p53 expression were investigated by immunohistochemical staining. Male Sprague-Dawley rats at the age of one week, five months, and two years were studied. C-Fos immunoreactivity was observed diffusely in gray matters in neonatal rats, preferentially located in deep dorsal horn and around central canal. Compared with those of neonatal rats, immunoreactive cells decreased prominently in adult rats. In aged rats, these cells were not seen in any segments. In a transverse section, spatial expression of Bcl-2 and Bax proteins showed a diffuse distribution pattern with immunore-activity more prominent in the anterior horn. Continuing expression of these proteins was shown in each age group. In adult rats, Bcl-2 immunoreactivity was decreased drastically compared to that of neonatal rats. The immunoreactivity was higher in aged than in adult rats, but the number of immunoreactive cells was not different between aged and neonatal rats. The number of Bax-immunoreactive cells was greater in adult than in neonatal rats; in aged rats, it was similar with that of adult rats. The spinal cords of neonatal rats were not p53-immunoreactive, though p53-positive cells were detected in all segments of adult spinal cord. P53-positive cells were stained along the cellular margin, with a pale central portion. The pattern of p53 immunoreactivity in adult and aged rats was similar; the number of p53-positive cells, however, was higher in aged rats than in adult. In conclusion, we demonstrated that the expression patterns of c-Fos, Bcl-2, Bax, and p53 proteins in rat spinal cord change during normal aging for the first time.