Memantine Administration Enhances Glutamatergic and GABAergic Pathways in the Human Hippocampus of Alzheimer's Disease Patients

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10499711" target="_blank" >RIV/00179906:_____/25:10499711 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378041:_____/25:00638016 RIV/61383082:_____/25:00001523 RIV/00216208:11110/25:10499711 RIV/00216208:11120/25:43928625 a 2 dalších

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kXvTRzMEQ3" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kXvTRzMEQ3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/pmic.70006" target="_blank" >10.1002/pmic.70006</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Memantine Administration Enhances Glutamatergic and GABAergic Pathways in the Human Hippocampus of Alzheimer's Disease Patients

Popis výsledku v původním jazyce

One of the traditional treatments in Alzheimer&apos;s disease (AD) is administration of memantine, the NMDA receptor antagonist. However, the molecular mechanism of the complex memantine action and the impact on the hippocampal proteome in humans is unknown. In this study, hippocampal proteins extracted from formalin-fixed paraffin-embedded post mortem tissues obtained from healthy donors (n = 15), AD patients not treated with memantine (n = 11), and AD patients treated with memantine (n = 8) were investigated using tandem mass tag (TMT)-based quantitative proteomics. Memantine medication induced subtle but distinct changes in the hippocampal proteome in AD patients. Although it did not prevent the metabolic and physiologic decline associated with AD pathology, memantine administration upregulated several mitochondrially encoded proteins and mitigated the proteomic pattern of activated phagocytes. Furthermore, memantine specifically enhanced the expression of postsynaptic glutamatergic and GABAergic receptors and components of the respective pathways without affecting presynaptic proteome. This suggests that memantine treatment in AD patients not only alleviates excitotoxic stress by inhibiting NMDA receptor activity, but also triggers broader adaptations in the synaptic signaling and plasticity.

Název v anglickém jazyce

Memantine Administration Enhances Glutamatergic and GABAergic Pathways in the Human Hippocampus of Alzheimer's Disease Patients

Popis výsledku anglicky

One of the traditional treatments in Alzheimer&apos;s disease (AD) is administration of memantine, the NMDA receptor antagonist. However, the molecular mechanism of the complex memantine action and the impact on the hippocampal proteome in humans is unknown. In this study, hippocampal proteins extracted from formalin-fixed paraffin-embedded post mortem tissues obtained from healthy donors (n = 15), AD patients not treated with memantine (n = 11), and AD patients treated with memantine (n = 8) were investigated using tandem mass tag (TMT)-based quantitative proteomics. Memantine medication induced subtle but distinct changes in the hippocampal proteome in AD patients. Although it did not prevent the metabolic and physiologic decline associated with AD pathology, memantine administration upregulated several mitochondrially encoded proteins and mitigated the proteomic pattern of activated phagocytes. Furthermore, memantine specifically enhanced the expression of postsynaptic glutamatergic and GABAergic receptors and components of the respective pathways without affecting presynaptic proteome. This suggests that memantine treatment in AD patients not only alleviates excitotoxic stress by inhibiting NMDA receptor activity, but also triggers broader adaptations in the synaptic signaling and plasticity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Proteomics

ISSN

1615-9853

e-ISSN

1615-9861

Svazek periodika

25

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

8

Strana od-do

42-49

Kód UT WoS článku

001525456600001

EID výsledku v databázi Scopus

2-s2.0-105010136089