Outline Enhancement of endogenous neuroprotective mechanisms – therapeutic strategies in brain damage [supervisors: prof. dr hab. Justyna Rogalska, NCU/prof. Karol Dokładny, University of New Mexico, USA]

The research planned to be performed under the PhD thesis is the part of the Emerging Field project: “New insight into chronic diseases: from risk factors, through prevention, diagnosis to treatment”

The pathophysiology of neurological disorders involves deleterious changes in cellular homeostasis. The mechanisms that lead to neuronal injury are complex and multifactorial. During these diseases the cellular functions can be disturbed by excitotoxicity, overproduction of reactive oxygen species or inflammation.

Neurons have developed their own endogenous cellular protective systems. The chronicity of neurodegenerative diseases allows the brain to engage compensatory mechanisms to counteract neuronal damage. Some of them are preventing cell death and others are allowing functional recovery after injury. The endogenous neuroprotective factors involved in neurons survival, include neurotrophic factors and their signalling pathways, processes regulating the redox status, and different pathways regulating cell death. Improving the effectiveness of this natural protection might help the remaining neural circuits to compensate for lost or broken circuits and enhance overall network performance and neurological function. The high efficiency of these mechanisms is crucial for cell survival. However, over time, these compensatory mechanisms can fail, and some may even become co-pathogenic. From a therapeutic perspective, it is crucial to determine how to encourage the neuroprotective mechanisms or alleviate the pathogenic once.

The research will focus on interaction of cerebrovascular disease e.g. stroke and neurodegeneration. It seems that new therapeutic targets could include protection of the endothelium, the blood-brain barrier, and other components of the neurovascular unit. Previous studies have shown that the activation of mineralocorticoid receptors (MR) raise the chance of neuronal survival, suggest­ing that it presents an adaptive mechanism, activated in response to damage. However, some data demonstrate that increased hippocampal MR expression is associated with a shift towards increased expression of pro-inflammatory genes at the expense of anti-inflammatory factors. As the consequence the inflammation-induced injury of vascular system can develop. Thus the protective role of MR receptors is not clear-cut. In order to develop effective therapies based on the properties of the described receptors, it is crucial to elucidate the consequences of MR activity under pathological conditions in the nervous system. There are no detailed, molecular studies focusing on processes occurring in the neurons after MR activation.

The aim of the project is to evaluate methods of the encouragement of endogenous mechanisms to compensate for lost or broken neural circuits. The state-of-the-art technologies will be used including molecular techniques (e.g. qRT-PCR, Bio-Plex Multiplex immunoassays, Flow cytometry), biochemical analysis and spectrophotochemical techniques; cell culture techniques; microscopy (confocal, TEM - transmission electron microscope); experimental techniques on animals (behavioural tests, electrophysiology).

Our foreign partner prof. Karol Dokladny, who is a physiologist will manage the part of the project concerning the neurovascular interaction and inflammation. Due to our interdisciplinarity (biology, medicine), we can look at neurodegenerative diseases in an innovative, multidirectional way. The identification of neuronal adaptive processes may facilitate the design of novel drugs that mimic the self-protective capacity of the brain or develop/improve the therapies to encourage the adaptive mechanisms.

What is funded

A doctoral student who does not hold a degree of doctor shall receive a doctoral scholarship.

The amount of a monthly doctoral scholarship shall be at least:1) 37% of a professor’s salary – up to the month in which the mid-term evaluation was conducted*; 2) 57% of a professor’s salary – after the month in which the mid-term evaluation was conducted*.

[*According to the legal status in 2020, the scholarship is gross: 1) 2.371,70 PLN, 2) 3.653,70 PLN.]

Duration

4 years.

Eligibility

A Master degree (a magister or a magister inżynier degree) or an equivalent degree, or the diploma, entitling to apply for the award of a degree of doctor in the country in the education system of which the higher education institution which issued it operates.

Taking part in the recruitment process.