Projects / Programmes
Involvement of PACAP in Alzheimer disease and depression: a postmortem human brain study
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Public mental health, Alzheimer disease, depression, aging of world population, neurodegenerative disorders, socioeconomic burden, brain disease, solutions, development of novel terapeutic targets, an integrated approach to solving a problem of today's society
Researchers (5)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
13310 |
PhD Gorazd Drevenšek |
Neurobiology |
Researcher |
2020 - 2023 |
329 |
| 2. |
55045 |
Zala Slabe |
Neurobiology |
Researcher |
2020 - 2023 |
9 |
| 3. |
52101 |
PhD Dick Frans Swaab |
Neurobiology |
Head |
2020 - 2023 |
236 |
| 4. |
21503 |
PhD Maja Zorović |
Neurobiology |
Researcher |
2020 - 2023 |
71 |
| 5. |
08289 |
PhD Marko Živin |
Neurobiology |
Researcher |
2020 - 2023 |
233 |
Organisations (1)
Abstract
Background. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is involved in the stress response and presumed to play a key role in mood disorders and in neurodegeneration. In rodents PACAP is expressed and released in many brain areas and can bind to multiple receptors. Information on PACAP in the human brain in health and disease is lacking. Methods. We will firstly determine in postmortem human brain the immunocytochemical localization of PACAP throughout the hypothalamus. Subsequently, we will measure in the paraventricular nucleus (PVN) of the hypothalamus, the motor of the stress response, changes in the amount of PACAP in Major depressive disorder (MDD) and bipolar disorder (BD) compared to matched controls. In addition, we will determine PACAP in the PVN of an unique cohort of Alzheimer (AD) patients with and without depression. Finally, the alterations in the expression of PACAP receptors PAC1, VPAC1, VPAC2 and CD38 will be determined in MDD and BD by qPCR in the prefrontal cortex (PFC), which is one of the main release sites of this neuropeptide. Aim The present study will start, therefore, with a systematic immunocytochemical description of the distribution of PACAP cell bodies, fibers and terminals in the hypothalamus. Subsequently we will determine by quantitative immunocytochemistry changes in PACAP in the PVN in MDD and BD. In addition, PACAP changes will be determined in the PVN in a unique cohort of AD patients that were followed for the presence or absence of depressive symptoms. PACAP in the PVN has never been determined in depressed and non-depressed AD patients nor in MDD patients. Moreover, we will determine by qPCR the alterations in PACAP and its receptors in two PFC areas, the DLPFC and ACC in MDD and BD. Special attention will be paid to the possible presence of sex difference and the relationship to psychotic features and suicide. Hypotheses: H1. After immunocytochemical staining (ICC) of a human tissue with antibody Rabbit anti-PACAP-38 (T-4473), there will be staining of neurons and fibers in the paraventricular nucleus of the hypothalamus. H2. There will be differences in the hypothalamus between men and women; women are expected to have more PACAP staining present in the paraventricular nucleus. H3. There will be more staining in patients with major depressive disorder (MDD) than in control, and it is expected that the paraventricular nucleus of female MDD patients will be more stained. H4. There will be more staining in patients with bipolar disorder (BD) than in control, and it is expected that the paraventricular nucleus of female BD patients will be more stained. H5.There will be a higher expression of PACAP in Alzheimer patients with major depressive disorder. H6. There will be lower expression in those without major depressive disorder. H7. The expectation is that control patients will have an even lower level of expression of PACAP than Alzheimer patients with and without a Major Depressive Disorder. Discussion. Our results can support a crucial role of PACAP in mood disorders, possibly by stimulation of the HPA-axis, through activation of corticotropin-releasing hormone (CRH) neurons. PACAP may be a novel therapeutic target for neurodegeneration, mood disorders, especially in BD and depression in AD.
