PMID- 24094876
OWN - NLM
STAT- MEDLINE
DCOM- 20140721
LR  - 20211203
IS  - 1873-3360 (Electronic)
IS  - 0306-4530 (Linking)
VI  - 38
IP  - 12
DP  - 2013 Dec
TI  - TNF-alpha and its receptors modulate complex behaviours and neurotrophins in 
      transgenic mice.
PG  - 3102-14
LID - S0306-4530(13)00329-6 [pii]
LID - 10.1016/j.psyneuen.2013.09.010 [doi]
AB  - Tumour necrosis factor-alpha (TNF-alpha) plays an important role not only in immunity but 
      also in the normal functioning of the central nervous system (CNS). At 
      physiological levels, studies have shown TNF-alpha is essential to maintain synaptic 
      scaling and thus influence learning and memory formation while also playing a 
      role in modulating pathological states of anxiety and depression. TNF-alpha signals 
      mainly through its two receptors, TNF-R1 and TNF-R2, however the exact role that 
      these receptors play in TNF-alpha mediated behavioural phenotypes is yet to be 
      determined. METHODS: We have assessed TNF(-/-), TNF-R1(-/-) and TNF-R2(-/-) mice 
      against C57BL/6 wild-type (WT) mice from 12 weeks of age in order to evaluate 
      measures of spatial memory and learning in the Barnes maze (BM) and Y-maze, as 
      well as other behaviours such as exploration, social interaction, anxiety and 
      depression-like behaviour in a battery of tests. We have also measured 
      hippocampal and prefrontal cortex levels of the neurotrophins nerve growth factor 
      (NGF) and brain derived neurotrophic factor (BDNF) as well as used 
      immunohistochemical analyses to measure number of proliferating cells (Ki67) and 
      immature neurons (DCX) within the dentate gyrus. RESULTS: We have shown that 
      young adult TNF(-/-) and TNF-R1(-/-) mice displayed impairments in learning and 
      memory in the BM and Y-maze, while TNF-R2(-/-) mice showed good memory but slow 
      learning in these tests. TNF(-/-)and TNF-R2(-/-) mice also demonstrated a 
      decrease in anxiety like behaviour compared to WT mice. ELISA analyses showed 
      TNF(-/-) and TNF-R2(-/-) mice had lower levels of NGF compared to WT mice. 
      CONCLUSION: These results indicate that while lack of TNF-alpha can decrease 
      anxiety-like behaviour in mice, certain basal levels of TNF-alpha are required for 
      the development of normal cognition. Furthermore our results suggest that both 
      TNF-R1 and TNF-R2 signalling play a role in normal CNS function, with knockout of 
      either receptor impairing cognition on the Barnes maze.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Camara, Marie Lou
AU  - Camara ML
AD  - Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, 
      SA, Australia; Discipline of Anatomy, School of Medicine, James Cook University, 
      Townsville, QLD, Australia.
FAU - Corrigan, Frances
AU  - Corrigan F
FAU - Jaehne, Emily J
AU  - Jaehne EJ
FAU - Jawahar, M Catharine
AU  - Jawahar MC
FAU - Anscomb, Helen
AU  - Anscomb H
FAU - Koerner, Heinrich
AU  - Koerner H
FAU - Baune, Bernhard T
AU  - Baune BT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130920
PL  - England
TA  - Psychoneuroendocrinology
JT  - Psychoneuroendocrinology
JID - 7612148
RN  - 0 (Dcx protein, mouse)
RN  - 0 (Doublecortin Protein)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tnfrsf1a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Anxiety/psychology
MH  - Behavior, Animal/*physiology
MH  - Depression/psychology
MH  - Doublecortin Protein
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Exploratory Behavior/physiology
MH  - Female
MH  - Immunohistochemistry
MH  - Interpersonal Relations
MH  - Learning/physiology
MH  - Male
MH  - Maze Learning/physiology
MH  - Memory/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Motor Activity/physiology
MH  - Nerve Growth Factors/*metabolism
MH  - Receptors, Tumor Necrosis Factor/genetics/*physiology
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type II/metabolism
MH  - Recognition, Psychology/physiology
MH  - Signal Transduction/physiology
MH  - Tumor Necrosis Factor-alpha/genetics/*physiology
OTO - NOTNLM
OT  - Anxiety
OT  - Cognition
OT  - Depression
OT  - Neurogenesis
OT  - Neurotrophins
OT  - Sociability
OT  - TNF-R1
OT  - TNF-R2
OT  - TNF-alpha
EDAT- 2013/10/08 06:00
MHDA- 2014/07/22 06:00
CRDT- 2013/10/08 06:00
PHST- 2013/04/04 00:00 [received]
PHST- 2013/09/09 00:00 [revised]
PHST- 2013/09/09 00:00 [accepted]
PHST- 2013/10/08 06:00 [entrez]
PHST- 2013/10/08 06:00 [pubmed]
PHST- 2014/07/22 06:00 [medline]
AID - S0306-4530(13)00329-6 [pii]
AID - 10.1016/j.psyneuen.2013.09.010 [doi]
PST - ppublish
SO  - Psychoneuroendocrinology. 2013 Dec;38(12):3102-14. doi: 
      10.1016/j.psyneuen.2013.09.010. Epub 2013 Sep 20.