Alzheimer risk factors age and female sex induce cortical Aβ aggregation by raising extracellular zinc [Alzheimer risk factors age and female sex induce cortical A beta aggregation by raising extracellular zinc]

Datki, Zsolt ✉ [Datki, Zsolt László (neurobiológia), szerző] Pszichiátriai Klinika (SZTE / SZAOK); Galik-Olah, Zita [Oláh, Zita (Kutató Biológus), szerző] Pszichiátriai Klinika (SZTE / SZAOK); Janosi-Mozes, Emese [Jánosi-Mózes, Emese (Neurobiológus), szerző] Pszichiátriai Klinika (SZTE / SZAOK); Szegedi, Viktor [Szegedi, Viktor (Idegtudomány), szerző] Élettani, Szervezettani és Idegtudományi Tanszék (SZTE / TTIK / BI); Kalman, Janos [Kálmán, János (Pszichiátria), szerző] Pszichiátriai Klinika (SZTE / SZAOK); Hunya, Ákos Gábor [Hunya, Ákos (neurobiológia), szerző] Orvosi Vegytani Intézet (SZTE / SZAOK); Fulop, Livia [Fülöp, Lívia (Neurodegeneratív ...), szerző] Orvosi Vegytani Intézet (SZTE / SZAOK); Tamano, Haruna; Takeda, Atsushi; Adlard, Paul A.; Bush, Ashley I. ✉

Angol nyelvű Szakcikk (Folyóiratcikk) Tudományos
Megjelent: MOLECULAR PSYCHIATRY 1359-4184 1476-5578 25 (11) pp. 2728-2741 2020
  • SJR Scopus - Cellular and Molecular Neuroscience: D1
  • Általános orvostudomány
  • Biológiai tudományok
  • Klinikai orvostan
  • Pszichiátria
  • Pszichiátriai betegségek
Aging and female sex are the major risk factors for Alzheimer's disease and its associated brain amyloid-beta (A beta) neuropathology, but the mechanisms mediating these risk factors remain uncertain. Evidence indicates that A beta aggregation by Zn(2+)released from glutamatergic neurons contributes to amyloid neuropathology, so we tested whether aging and sex adversely influences this neurophysiology. Using acute hippocampal slices, we found that extracellular Zn2+-elevation induced by high K(+)stimulation was significantly greater with older (65 weeks vs 10 weeks old) rats, and was exaggerated in females. This was driven by slower reuptake of extracellular Zn2+, which could be recapitulated by mitochondrial intoxication. Zn2+:A beta aggregates were toxic to the slices, but A beta alone was not. Accordingly, high K(+)caused synthetic human A beta added to the slices to form soluble oligomers as detected by bis-ANS, attaching to neurons and inducing toxicity, with older slices being more vulnerable. Age-dependent energy failure impairing Zn(2+)reuptake, and a higher maximal capacity for Zn(2+)release by females, could contribute to age and sex being major risk factors for Alzheimer's disease.
Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
2022-10-02 22:16