PMID- 36856802
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20230314
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 240
IP  - 4
DP  - 2023 Apr
TI  - Intranasal administration of interleukin-4 ameliorates depression-like behavior 
      and biochemical alterations in mouse submitted to the chronic unpredictable mild 
      stress: modulation of neuroinflammation and oxidative stress.
PG  - 935-950
LID - 10.1007/s00213-023-06336-4 [doi]
AB  - Physical and psychological stress modulates the hypothalamic pituitary adrenal 
      (HPA) axis, and the redox and inflammatory systems. Impairments in these systems 
      have been extensively reported in major depression (MD) patients. Therefore, our 
      study aimed to investigate the effects of the intranasal administration of 
      interleukin-4 (IL-4) in mice with depressive-like behavior induced by chronic 
      unpredictable mild stress (CUMS) for 28 days. On the 28th day, mice received IL-4 
      intranasally (1 ng/mouse) or vehicle (sterile saline), and after 30 min, they 
      were submitted to behavioral tests or euthanasia for blood collection and removal 
      of the adrenal glands, axillary lymph nodes, spleen, thymus, prefrontal cortices 
      (PFC), and hippocampi (HC). A single administration of IL-4 reversed CUMS-induced 
      depression-like behavior in the tail suspension test and splash test, without 
      evoking locomotor changes. IL-4 administration reduced the plasma levels of 
      corticosterone and the increased weight of suprarenal glands in stressed mice. 
      Moreover, IL-4 restored the expression of nuclear factor erythroid 2-related 
      factor 2 (NRF2), nuclear factor kappa B (NF-kB), interleukin 1 beta (IL-1beta), 
      IL-4, brain derived neurotrophic factor (BDNF), and indoleamine 2,3-dioxygenase 
      (IDO) in the PFC and HC and modulated oxidative stress markers in these brain 
      structures in stressed mice. Our results showed for the first time the 
      antidepressant-like effect of IL-4 through the modulation of neuroinflammation 
      and oxidative stress. The potential effect of IL-4 administered intranasally 
      arises as an innovative strategy for MD treatment.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Smaniotto, Thiago Angelo
AU  - Smaniotto TA
AD  - Technology Development Center, Division of Biotechnology, Neurobiotechnology 
      Research Group, Federal University of Pelotas, Pelotas, RS, 96010900, Brazil.
FAU - Casaril, Angela Maria
AU  - Casaril AM
AD  - Technology Development Center, Division of Biotechnology, Neurobiotechnology 
      Research Group, Federal University of Pelotas, Pelotas, RS, 96010900, Brazil.
FAU - de Andrade Lourenco, Darling
AU  - de Andrade Lourenco D
AD  - Technology Development Center, Division of Biotechnology, Neurobiotechnology 
      Research Group, Federal University of Pelotas, Pelotas, RS, 96010900, Brazil.
FAU - Sousa, Fernanda S
AU  - Sousa FS
AD  - Technology Development Center, Division of Biotechnology, Cancer Biotechnology 
      Laboratory, Federal University of Pelotas, Pelotas, RS, 96010900, Brazil.
FAU - Seixas, Fabiana K
AU  - Seixas FK
AD  - Technology Development Center, Division of Biotechnology, Cancer Biotechnology 
      Laboratory, Federal University of Pelotas, Pelotas, RS, 96010900, Brazil.
FAU - Collares, Tiago
AU  - Collares T
AD  - Technology Development Center, Division of Biotechnology, Cancer Biotechnology 
      Laboratory, Federal University of Pelotas, Pelotas, RS, 96010900, Brazil.
FAU - Woloski, Rafael
AU  - Woloski R
AD  - Technology Development Center, Division of Biotechnology, Bioinformatics and 
      Proteomics Laboratory, Federal University of Pelotas, Pelotas, RS, 96010900, 
      Brazil.
FAU - da Silva Pinto, Luciano
AU  - da Silva Pinto L
AD  - Technology Development Center, Division of Biotechnology, Bioinformatics and 
      Proteomics Laboratory, Federal University of Pelotas, Pelotas, RS, 96010900, 
      Brazil.
FAU - Alves, Diego
AU  - Alves D
AD  - Center of Chemical, Pharmaceutical and Food Sciences, Laboratory of Clean Organic 
      Synthesis, Federal University of Pelotas, Pelotas, RS, 96010900, Brazil.
FAU - Savegnago, Lucielli
AU  - Savegnago L
AD  - Technology Development Center, Division of Biotechnology, Neurobiotechnology 
      Research Group, Federal University of Pelotas, Pelotas, RS, 96010900, Brazil. 
      luciellisavegnago@yahoo.com.br.
AD  - Center of Chemical, Pharmaceutical and Food Sciences, Laboratory of Clean Organic 
      Synthesis, Federal University of Pelotas, Pelotas, RS, 96010900, Brazil. 
      luciellisavegnago@yahoo.com.br.
LA  - eng
PT  - Journal Article
DEP - 20230301
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 207137-56-2 (Interleukin-4)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Depression/psychology
MH  - *Interleukin-4
MH  - Neuroinflammatory Diseases
MH  - Administration, Intranasal
MH  - Oxidative Stress
MH  - Stress, Psychological/psychology
MH  - Disease Models, Animal
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Hippocampus
OTO - NOTNLM
OT  - CUMS
OT  - HPA axis
OT  - Interleukin-4
OT  - Neuroinflammation
OT  - Neuromodulation
OT  - Oxidative stress
EDAT- 2023/03/02 06:00
MHDA- 2023/03/15 06:00
CRDT- 2023/03/01 11:13
PHST- 2022/03/30 00:00 [received]
PHST- 2023/02/03 00:00 [accepted]
PHST- 2023/03/02 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/03/01 11:13 [entrez]
AID - 10.1007/s00213-023-06336-4 [pii]
AID - 10.1007/s00213-023-06336-4 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2023 Apr;240(4):935-950. doi: 
      10.1007/s00213-023-06336-4. Epub 2023 Mar 1.