Title:

The role of mouse zinc-sensing GPR39 receptor in memory functions associated with Alzheimer’s disease

Author:

Rychlik, Michał

Subject:

hippocampus ; dementia ; episodic memory ; memantine ; trace metals

Abstract:

In the mammalian brains synaptic zinc acts as a neuromodulator and a neurotransmitter. Synapses are also where toxic forms of amyloid beta (Aβ) are formed, which is the first step of a pathological cascade leading to Alzheimer’s dementia (AD) in humans. Evidence gathered over the span of last 25 years shows that synaptic zinc exacerbates the effects of Aβ; and, that by binding zinc Aβ disrupts the physiological functions of the ion. One of the most understudied physiological functions in this regard is neurotransmission through the zincergic GPR39 receptor. The main aim of this work was to establish whether GPR39 modulates memory in mice, especially: an analogue of declarative memory affected in early stages of AD in humans i.e. episodic memory. Secondly, the effects of both acute and chronic pharmacological manipulations of GPR39 with its agonist (TC-G 1008) on declarative memory of mice were investigated; as well as, the effect of GPR39 knock-out (KO) on the action of memantine – a drug used in pharmacotherapy of AD. Lastly, the procognitive potential of both drugs was tested in a model of neurodegeneration – the constitutive heterozygous KO of brain-derived neurotropic factor (Bdnf).

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

farmakologia ; neurologia

Degree grantor:

Rada Dyscypliny Nauki farmaceutyczne

Promoter:

Młyniec, Katarzyna

Date:

2022

Date issued:

2021

Type:

Praca doktorska

Call number:

ZB-135618

Language:

eng

Access rights:

nieograniczony