Vulnerability of adult hippocampus to toxicity after postnatal exposure of nursing male albino rats to iron overload : Histomorphometric and ultrastructural study

Abstract

Background: The association of iron overload with neurodegenerative diseases and cognitive deficits in aging were previous reported. Developing hippocampus is highly sensitive to changes in iron homeostasis that might lead to long term irreversible impact on its functions. Objective: To examine the possible histopathological changes in adult hippocampal subregions CA1, CA3 and DG subjected to excess iron administration at critical early postnatal life. Materials and Methods: 20 male rat pups weighing 50-55gm were selected and randomly divided into 2 groups (10 per each). The control received 0.5 ml normal saline intraperitoneally once daily for 21 consecutive days. Iron treated group received intraperitoneal injection of ferrous sulfate dissolved in 0.5 ml normal saline at a dose of 3 mg/kg/day for 21 days. After sacrifice, brain specimens were processed for histomorphometric and ultrastructural study. Results: Iron deposits were reported only in treated group using Prussian blue. Obvious degeneration of principal neurons with significant decrease in their number and increased immunoreactivity to caspase 3 and glial fibrillary acid protein (GFAP)were observed in all studied subfields of iron treated hippocampus. Astrogliosis, astrocyte damage and disruption of blood brain barrier were also noticed. Conclusion: There was pronounced degenerative changes in all studied subregions of iron treated hippocampus indicating its extreme sensitivity to changes in iron homeostasis, hence iron overload could be considered highly toxic insult on growing hippocampal tissue.

Acetylated oligopeptide and N‐acetylcysteine protect against iron overload‐induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2/HO‐1 and downregulation of MMP‐9/TIMP‐1 and GFAP

“…The antiapoptotic effect of NAC was also reported by Xiong et al62 Additionally, immunohistochemical examination of anti-claudin showed low expression in the DG region of the iron-treated group. This outcome is in line with the earlier research conducted by Dawood et al10 Claudins, among other components, form the backbone of tight junctions in the BBB. Iron overload causes BBB disruption, permeability disturbance, and a decrease in the expression of tight junction proteins.…”

“…In addition, the oxidative damage that occurs after iron overload is thought to induce apoptosis, which in turn boosts neurodegeneration 22 . Members of the caspase family are proteolytic enzymes that induce apoptosis via extrinsic and intrinsic apoptotic pathways 10 . Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that maintains astrocyte structure and formation.…”

“…The hippocampus is an essential neural region responsible for higher neural functions like long‐term memory and spatial navigation, emotions, learning, and social behavior. It is very susceptible to oxidative stress, and iron overload can lead to degenerative changes in the hippocampal subfields 10 …”

“…22 Members of the caspase family are proteolytic enzymes that induce apoptosis via extrinsic and intrinsic apoptotic pathways. 10 Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that maintains astrocyte structure and formation. Iron deposition in the hippocampus leads to the degeneration of principal neurons and increased immunoreactivity to GFAP.…”

“…Iron deposition in the hippocampus leads to the degeneration of principal neurons and increased immunoreactivity to GFAP. 10 N-acetylcysteine is a powerful antioxidant that is derived from Lcysteine and is widely used as a mucolytic. It exerts its effects either directly by quenching some oxidants or indirectly by acting as a precursor of cysteine, which is the rate-limiting step in glutathione production.…”