Search

Glutamate is a major excitatory neurotransmitter that is stored in vesicles located in the presynaptic terminal. Glutamate is transported into vesicles via the vesicular glutamate transporter (VGLUT). In the present study, the age‑associated changes of the major VGLUTs, VGLUT1 and VGLUT2, in the hippocampus were investigated, based on immunohistochemistry and western blot analysis at postnatal month 1 (PM1; adolescent), PM6, PM12 (adult group), PM18 and PM24 (the aged groups). VGLUT1 immunoreactivity was primarily detected in the mossy fibers, Schaffer collaterals and stratum lacunosum‑moleculare. By contrast, VGLUT2 immunoreactivity was observed in the granule cell layer and the outer molecular layer of the dentate gyrus, stratum pyramidale, Schaffer collaterals and stratum lacunosum‑moleculare in the hippocampal CA1‑3 regions. VGLUT1 immunoreactivity and protein levels remained constant across all age groups. However, VGLUT2 immunoreactivity and protein levels decreased in the PM3 group when compared with the PM1 group. VGLUT2 immunoreactivity and protein levels were not altered in the PM12 group; however, they increased in the PM18 group. In addition, in the PM18 group, highly immunoreactive VGLUT2 cells were also identified in the stratum radiatum and oriens of the hippocampal CA1 region. In the PM24 group, VGLUT2 immunoreactivity and protein levels were significantly decreased and were the lowest levels observed amongst the different groups. These results suggested that VGLUT1 may be less susceptible to the aging process; however, the increase of VGLUT2 in the non‑pyramidal cells in the PM18 group, and the consequent decrease in VGLUT2, may be closely linked to age‑associated memory impairment in the hippocampus. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of hypothyroidism on cyclooxygenase‑2 (COX‑2) and pro‑inflammatory cytokines in the dentate gyrus to elucidate the roles of COX‑2 in the hypothyroid hippocampus. Hypothyroidism was induced in rats by treating with 0.03% 2‑mercapto‑1‑methyl‑imidazole dissolved in drinking water for 5 weeks. The animals were sacrificed at 12 weeks of age. Hypothyroidism rats exhibited decreased triiodothyronine and thyroxine levels in the serum, while the levels of thyroid‑stimulating hormone and the weight of thyroid glands were significantly higher in the hypothyroid rats compared with those in the vehicle‑treated group. COX‑2 immunoreactivity was significantly increased in the hippocampal CA2/3 region and the dentate gyrus compared with the vehicle‑treated group. Levels of pro‑inflammatory cytokines including interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α were significantly higher in the hippocampal homogenates of hypothyroid rats. Cell proliferation and neuroblast differentiation based on Ki67 and doublecortin immunohistochemistry were decreased in the dentate gyrus of hypothyroid rats compared with those in the vehicle‑treated group. These results suggested that hypothyroidism‑mediated COX‑2 expression affected hippocampal plasticity by upregulating the levels of pro‑inflammatory cytokines in the hippocampus. Therefore, COX‑2 may be suggested as a candidate molecule for preventing hypothyroidism‑induced neurological side effects. [ABSTRACT FROM AUTHOR]