Original articleTNFα Signaling in Depression and Anxiety: Behavioral Consequences of Individual Receptor Targeting
Section snippets
Mouse Strains and Genotyping
Mice carrying the Tnfrsf1atm1Mak mutation (TNFR1−/−; Pfeffer et al 1993) and Tnfrsf1btm1Mwm (TNFR2−/−; Erickson et al 1994) mutations, respectively, were purchased from the Jackson Laboratory (Bar Harbor, Maine). Both strains have been back-crossed to C57Bl/6 mice for at least 10 generations and were maintained at the Jackson Laboratory by nullXnull sib breedings. Heterozygotes were produced by crosses with wild type C57Bl/6J mice, and these animals were then interbred to produce TNFR1−/− or
Expression of TNFR1 and TNFR2 in the Brain
To verify that TNFR1 and TNFR2 are expressed in brain, we compared mRNA expression levels for the two receptors in five brain regions using real-time PCR analysis (Figure 1). In addition, we tested whether levels of the less abundant receptor, TNFR2, were changed in TNFR1−/− brains. For TNFR1, significant differences were noted between brain regions (F[4,8] = 7.88, p < .01) in TNFR1+/+ mice, with highest expression levels in the brain stem (.658 ± .065) and lowest levels in the cerebellum (.250
Discussion
We examined the expression profiles of TNFR1 and TNFR2 in five major brain regions. The expression of TNFR1 varied among the regions, but both receptors were found throughout the brain. Overall, the level of TNFR1 was approximately 2.5-fold higher than that of TNFR2. These results are consistent with the report that TNFR1 and 2 are constitutively expressed by microglia, whereas astrocytes and oligodendrocytes only express TNFR1 (Dopp et al 1997). The high expression of TNFR1 in the brain stem
References (59)
- et al.
Further evidence for the depressive effects of cytokinesAnhedonia and neurochemical changes
Brain Behav Immun
(2002) Role of the serotonergic system in the forced swimming test
Neurosci Biobehav Rev
(1995)- et al.
Fear conditioning and latent inhibition in mice lacking the high affinity subclass of nicotinic acetylcholine receptors in the brain
Neuropharmacology
(2000) - et al.
Antibodies to lymphotoxin alpha (LT alpha) and LT beta recognize different glial cell types in the central nervous system
J Neuroimmunol
(1997) - et al.
Roles of tumor necrosis factor-alpha receptor subtypes in the pathogenesis of the tristetraprolin-deficiency syndrome
Blood
(2001) - et al.
An assessment of the effects of central interleukin-1beta, -2, -6, and tumor necrosis factor-alpha administration on some behavioural, neurochemical, endocrine and immune parameters in the rat
Neuroscience
(1998) Innate immunity at the forefront of psychoneuroimmunology
Brain Behav Immun
(2004)- et al.
Differential expression, cytokine modulation, and specific functions of type-1 and type-2 tumor necrosis factor receptors in rat glia
J Neuroimmunol
(1997) - et al.
Serum interleukin-6 concentration in schizophreniaElevation associated with duration of illness
Psychiatry Res
(1994) - et al.
Brain-derived TNFalpha mediates neuropathic pain
Brain Res
(1999)