Decreased levels of Brain-Derived Neurotrophic Factor (BDNF) are a common finding in schizophrenia. Another well-documented protein linked to schizophrenia is intracellular Ca2+-independent Phospholipase (PLA2). However, the potential association between PLA2 and BDNF with regard to schizophrenia has yet to be examined. In the present study, male and female BDNF knockout mice, a possible genetic model of schizophrenia, were exposed to prenatal stress and tested in the nest test, open field test and T-maze. Following behavioral tests, whole brain and plasma samples were harvested to measure the activity of PLA2. BDNF knockout mice showed cognitive deficits in the T-maze. Furthermore, there was a quadratic association of PLA2 with performance in the open field test. Moreover, BDNF deficiency and female sex were associated with elevated plasma PLA2 levels. The cognitive impairment of BDNF heterozygous mice as well as their increased PLA2 activity in plasma is consistent with findings in schizophrenia patients. The particular elevation of PLA2 activity in females may partly explain sex differences of clinical symptoms in schizophrenia (e.g. age of onset, severity of symptoms). Additionally, PLA2 was significantly correlated with body and adrenal weight after weaning, whereby the latter emphasizes the possible connection of PLA2 with steroidogenesis.

Brain Derived Neurotrophic Factor Deficiency is Associated with Cognitive Impairment and Elevated Phospholipase A2 Activity in Plasma of Mice / M. Schmidt, A.C. Rossetti, C. Brandwein, M.A. Riva, P. Gass, P. Elsner, J. Hesse-Macabata, U. Hipler, S. Smesny, B. Milleit. - In: NEUROSCIENCE. - ISSN 0306-4522. - 480:(2022), pp. 167-177. [10.1016/j.neuroscience.2021.11.024]

Brain Derived Neurotrophic Factor Deficiency is Associated with Cognitive Impairment and Elevated Phospholipase A2 Activity in Plasma of Mice

A.C. Rossetti
Secondo
;
M.A. Riva;
2022

Abstract

Decreased levels of Brain-Derived Neurotrophic Factor (BDNF) are a common finding in schizophrenia. Another well-documented protein linked to schizophrenia is intracellular Ca2+-independent Phospholipase (PLA2). However, the potential association between PLA2 and BDNF with regard to schizophrenia has yet to be examined. In the present study, male and female BDNF knockout mice, a possible genetic model of schizophrenia, were exposed to prenatal stress and tested in the nest test, open field test and T-maze. Following behavioral tests, whole brain and plasma samples were harvested to measure the activity of PLA2. BDNF knockout mice showed cognitive deficits in the T-maze. Furthermore, there was a quadratic association of PLA2 with performance in the open field test. Moreover, BDNF deficiency and female sex were associated with elevated plasma PLA2 levels. The cognitive impairment of BDNF heterozygous mice as well as their increased PLA2 activity in plasma is consistent with findings in schizophrenia patients. The particular elevation of PLA2 activity in females may partly explain sex differences of clinical symptoms in schizophrenia (e.g. age of onset, severity of symptoms). Additionally, PLA2 was significantly correlated with body and adrenal weight after weaning, whereby the latter emphasizes the possible connection of PLA2 with steroidogenesis.
BDNF; mouse model; phospholipase A2; polyunsaturated fatty acids; schizophrenia; Animals; Brain-Derived Neurotrophic Factor; Female; Humans; Male; Mice; Phospholipases A2; Cognition Disorders; Cognitive Dysfunction; Schizophrenia
Settore BIO/14 - Farmacologia
18-nov-2021
Article (author)
File in questo prodotto:
File Dimensione Formato  
NSC-20-1744_R3-2 (1).pdf

accesso aperto

Tipologia: Pre-print (manoscritto inviato all'editore)
Dimensione 4.48 MB
Formato Adobe PDF
4.48 MB Adobe PDF Visualizza/Apri
1-s2.0-S0306452221005832-main.pdf

solo utenti autorizzati

Tipologia: Publisher's version/PDF
Dimensione 714.55 kB
Formato Adobe PDF
714.55 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/929846
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact