Modulation of tyrosine hydroxylase gene expression in rat brain and adrenals by exposure to cold

Abstract

The long-term changes in tyrosine hydroxylase (TH) activity induced by chronic exposure to cold in brain noradrenergic neurons of the locus coeruleus (LC) were analyzed and compared to those measured in a peripheral tissue such as adrenals. This analysis was made possible at the level of one single tissue corresponding to one animal by the use of sensitive methods that allow assay of TH activity, protein, and mRNA levels in parallel from the same homogenate. The three parameters were measured in brain structures and adrenals of rats maintained at 4 degrees C during 4 days and were compared to those of control animals kept at normal housing temperature (22 degrees C). LC of rats exposed to cold contained 200% more TH mRNA than controls. The amount of TH protein in this area rose to as much as 164% that of controls. Similarly, the activity of the enzyme increased to 140% of the normal value. Thus, these observations show that 1) the increase in TH mRNA was much higher than the increase in protein levels, and that 2) the newly synthesized molecules have about the same activity as that present under normal conditions. In contrast to the LC, no variation of these parameters was observed in the substantia nigra. In the adrenals, the variations in the different parameters were qualitatively similar to that observed in the LC, although they were quantitatively higher: TH mRNA, TH protein, and TH activity levels were respectively 330%, 182%, and 167% that of control adrenals. Altogether, these results demonstrate that exposure to cold induces an alteration in TH synthesis in brain noradrenergic neurons as well as in adrenals.

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

“…The stressful event (forced swimming) combined with repeated i.p. injections resulted in increased activity of the LC NA system, evidenced by an increase of TH and galanin mRNA levels in the LC, in agreement with previous findings (Biguet et al, 1986;Berod et al, 1987;Richard et al, 1988;Austin et al, 1990;Holmes et al, 1995). Stress-induced hyperactivity of the LC neurons and increased release of NA have been proposed to contribute to development of human depression (Nestler et al, 1990; see Mongeau et al, 1997;Grant and Weiss, 2001;Morilak and Frazer, 2004).…”

Chronic Cold Stress Reduces the Spontaneous Activity of Ventral Tegmental Dopamine Neurons

“…These two effects may not be independent of each other, since increased burst-firing in LC neurons prolongs the inhibition of DA neurons following LC stimulation (Grenoff et al 1993). This, as well as differential changes in TH activity and gene expression in the LC and midbrain (Ortiz et al 1996;Richard et al 1988;Zigmond et al 1974) may contribute to the apparent persistence and sensitization of the activation of forebrain NE transmission versus the apparent adaptation of the mesolimbic/mesocortical DA systems. It is important to note, however, that changes in DA release cannot be easily predicted from changes in neuronal firing rate.…”

“…Previous work has shown that initial responses to cold-restraint include elevation of plasma corticosterone (e.g., Dallman et al 2000) increases in tyrosine hydroxylase mRNA and activity in the adrenal glands and locus coeruleus (Fluharty et al 1985;Richard et al 1988) and increases in release or turnover of cortical norepinephrine and dopamine (Dallman et al 2000;Dunn and File 1983;c.f., Stanford 1993). These and other effects such as increased vulnerability to gastric ulcers have led to the conclusion that this procedure represents a relatively severe stressor that affects not only the exquisitely sensitive mesocortical dopamine system but also mesolimbic and nigrostriatal DA systems (Dunn and File 1983).…”

Locus coeruleus stimulation by corticotropin-releasing hormone suppresses in vitro cellular immune responses

“…Relevant populations include patients experiencing chronic stress (Chapel1 et al, 1986;Richard et al, 1988;Melia and Duman, 199 l), or neuropsychiatric disorders that may be associated with a hypersection of CRH (Holsboer et al, 1984;Nemeroff et al, 1984;Gold et al, 1986) and CNS diseases that are associated with a depletion of locus coeruleus neurons (Tavalato and Argenteiro, 1980;Singh et al, 1987;Chan-Palay, 1991;German et al, 1992).…”

“…Electrophysiological studies show that the locus coeruleus is activated by CRH (Ehlers et al, 1983;Valentino et al, 1983;Foote, 1987, 1988;De Sarro et al, 1992) and exposure to noxious stimuli (Abercrombie and Jacobs, 1987). Furthermore, stressors increase activity of locus coeruleus neurons, as reflected by the expression of the immediate-early gene c-Fos (Pezzone et al, 1993) and the activity of tyrosine hydroxylase, the rate limiting enzyme for norepinephrine biosynthesis (Zigmond et al, 1974;Richard et al, 1988;Weiner et al, 1991;Melia et al, 1992). Therefore, the integrative reactivity of the locus coeruleus and its projections (for review, see Foote et al, 1983;Moore and Card, 1984;Aston-Jones et al, 199 1;Valentino et al, 1992) to sensory stimuli is the basis for the present hypothesis, which poses that activation of this nucleus is part of the neural circuit that modifies immunologic function.…”