Junichi Nomura

Projections of the vestibular nuclei to the thalamus in the rat: A Phaseolus vulgaris leucoagglutinin study

Injections of the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin were made into individual nuclei of the vestibular nuclear complex of the rat to identify specific projections to the thalamus. The results showed that the superior vestibular nucleus and the medial vestibular nucleus, especially its rostral‐to‐middle parts, project to the lateral part of the parafascicular thalamic nucleus (corresponding to the centromedian nucleus in primates), the transitional zone between the ventrolateral thalamic nucleus (VL) and the ventral posterolateral thalamic nucleus (VPL) (the region considered to be the nucleus ventralis intermedius of Vogt [Vogt C. 1909. La myeloarchitecture du thalamus du cercopitheque. J Psychol Neurol 12:285–324.]), the lateral part of the centrolateral thalamic nucleus and the dorsal part of the caudal VL; the spinal vestibular nucleus projects to the lateral part of the parafascicular thalamic nucleus, the transitional zone between the VL and the VPL, the caudal part of the ventrobasal complex, and the suprageniculate thalamic nucleus. These results suggest that vestibular information is transmitted not only to the cerebral cortex (mainly area 2V and area 3a) but also to the striatum. They also suggest that vestibular activity may affect gaze control by means of vestibulothalamocortical pathway in addition to vestibulo‐ocular and vestibulopremotoneuronal routes. J. Comp. Neurol. 407:318–332, 1999.

Long-Term Stress Degenerates, But Imipramine Regenerates, Noradrenergic Axons in the Rat Cerebral Cortex

Exposed to a forced walking stress for 2 weeks, some rats became persistently inactive (depression-model rats), whereas others gradually recovered from exhaustion (spontaneous recovery rats). We also studied rats exposed to short-term stress, rats without stress, and the model rats treated with imipramine or saline. We examined the density of noradrenergic axons in the frontal cortex using retrograde labeling of the locus coeruleus with horseradish peroxidase injected into the cortex and immunohistochemical staining of cortical axons with dopamine beta-hydroxylase antiserum. The density was significantly lower in the depression-model rats, but tended to be higher in the recovery rats and short-term stressed rats. Chronic treatment with imipramine significantly increased the density in the model rats. There was also a correlation between the density of noradrenergic axons and the recovery rate of activity. Our results suggest that cortical noradrenergic degeneration is involved in the pathogenesis of depression.

Potential antidepressant effects of lemon odor in rats

Antidepressant effects brought about by olfactory stimulation with various odorants were investigated with the forced swimming test, a reliable means for screening antidepressant effects. Lemon odor significantly reduced total immobility time and potentiated the imipramine-induced reduction of total immobility time in the test. This synergistic effect of lemon odor and imipramine was not due to lemon odor decreasing the metabolism of imipramine. Lemon odor decreased locomotor activity in the open field, suggesting its effects to differ from those of psychostimulants but to be similar to those of antidepressants. The effects of citral, which is one of the main components of lemon odor, were as strong as those of lemon odor. The remaining odorants tested in this study failed to have any effects on total immobility time in the forced swimming test or on locomotor activity in the open field.

Endocrine study of the maternity blues.

The relationship between several psychological variables and adrenocortical function of the blues is examined in a prospective study of 47 Japanese women. Psychological measures, including the psychiatric interview and assessment of the Schedule for Affective Disorders and Schizophrenia (SASD), the Research Diagnostic Criteria (RDC) and self-rating scales, were administered at the 36th week of pregnancy, on the 3rd or 4th day postnatal and one month after delivery. Twelve subjects (25.5%) were diagnosed as having the blues on the Steins scale. Women who developed the blues had significantly higher serum bound cortisol than the non-blues group. No significant correlation was obtained between the incidence of the blues and obstetric variables. At one month after delivery, four women (8.5%) were diagnosed as postpartum depression according to the RDC. Our finding that there was no consistent obstetric factor which predisposes women to develop the blues support the hypothesis that hyperadrenocorticalism is important in the genesis of this syndrome.

DEGENERATION OF LOCUS COERULEUS AXONS IN STRESS-INDUCED DEPRESSION MODEL

Antidepressants such as desipramine induce axonal regeneration of brain noradrenergic neurons. This novel action of antidepressants suggests the involvement of degeneration or retraction of brain noradrenergic axons in the pathophysiology of clinical depression. The present study was designed to further confirm this view in an animal model of stress-induced depression. The depression model was produced by exposing rats to prolonged forced walking stress. To see if axonal degeneration of noradrenergic neurons occurred in the depression model, the density of noradrenergic axons in the cerebral cortex was assessed by three different methods, antidromic stimulation technique, retrograde tracing with horseradish peroxidase and immunohistochemical staining with dopamine-beta-hydroxylase antiserum. These methods all assured of degenerative changes of noradrenergic axon terminals in the depression model. Furthermore, it was found that repeated treatments of the depression-model rats with imipramine could cause regeneration of cortical noradrenergic axons. These findings support the view that degeneration or retraction of noradrenergic axons is involved in the pathophysiology of depression.

Clinical and experimental studies on the pathogenesis of depression.

Abstract (1) Serum TSH responses to TRH showed abnormal patterns in terms of diminished, delayed and exaggerated responses in more than one third of the depressed patients. (2) These findings suggest the pathogenetic importance of the hypothalamo-pituitary dysfunction in depressed patients. Because of this, a number of patients, especially those with diminished and delayed TSH responses to TRH, are prone to develop latent hypothyroidism which might make them resistant to antidepressants. (3) To elucidate the underlying mechanism of these clinical findings, changes in brain monoamines of ‘depression model rats’ were examined by the histochemical fluorescence method. (4) Fluorescence intensity in nerve cells of the ascending NA system (A1, A2, A5, A6, A7) was markedly increased and fluorescence intensity in cell bodies (A12) and nerve terminals (ext. ME) of the tubero-infundibular DA system was decreased.

The influence of restraint stress on the expression of mRNAs for IL-6 and the IL-6 receptor in the hypothalamus and midbrain of the rat

Using the reverse transcriptase-polymerase chain reaction (RT-PCR), we investigated the influence of restraint stress on the expression of the mRNA for interleukin-6 (IL-6) and the mRNA for the IL-6 receptor (IL-6R) in the rat brain. After rats had been restrained for 4 hours, the hypothalamus and midbrain were removed at fixed intervals up to 24 hours, and levels of IL-6 mRNA and of IL-6R mRNA in these regions were determined by RT-PCR. Restraint stress significantly enhanced the expression of IL-6 mRNA and reduced that of IL-6R mRNA in the midbrain, whereas the stress caused the reduced expression of IL-6R mRNA without any change in the level of IL-6 mRNA in the hypothalamus. After the stress, the expression of mRNAs for IL-6 and IL-6R continued to diminish in both regions. These findings indicate that the levels of mRNAs for both of IL-6 and IL-6R in the rat brain can be influenced by restraint stress.

The expressions of mRNAs for interleukin-6 (IL-6) and the IL-6 receptor (IL-6R) in the rat hypothalamus and midbrain during restraint stress.

Over the past few years, it has been reported that physical and psychological stress elevate plasma interleukin-6 (IL-6), and that neural cells can produce IL-6 and have receptors for IL-6 (IL-6R). However, it is unknown whether IL-6 plays a role in regulating the functions of neural cells in response to stress. We demonstrated recently, using the reverse transcriptase-polymerase chain reaction (RT-PCR), that the levels of mRNAs for IL-6 and IL-6R in the rat brain are changed by restraint stress for four hours. In the present study, we investigated the expression of mRNAs for IL-6 and the IL-6R in the rat hypothalamus and midbrain during restraint stress. After rats had been restrained for 10, 30, 60, 120 or 240 min, the hypothalamus and midbrain were removed immediately and levels of IL-6 mRNA and of IL-6R mRNA in these regions were determined by RT-PCR. The expression of mRNAs for IL-6 and IL-6R in both regions was reduced after short-term (30-60 min) restraint stress and tended to return toward the control level after 120 min restraint stress. After long-term (240 min) restraint stress, the level of IL-6 mRNA was significantly increased in the midbrain, while the level of IL-6R mRNA was significantly reduced in both regions. These findings suggest that the need for IL-6 might decline after short-term restraint stress and, moreover, that the synthesis and secretion of IL-6 might be enhanced and IL-6 might be needed as a neurotrophic factor in the midbrain after long-term stress.

The vestibular nuclei of the rat project to the lateral part of the thalamic parafascicular nucleus (centromedian nucleus in primates).

To clarify the vestibular projections to the centromedian-parafascicular nuclear complex, the Phaseolus vulgaris leucoagglutinin (PHA-L) and horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP), tracing studies have been done in rats. The data demonstrated that the lateral parafasicular nucleus received vestibular afferents mainly from the ventral part of medial vestibular nucleus, and the superior and inferior vestibular nuclei, with an ipsilateral predominance. These findings suggest the vestibular influence to the motor loop of the basal ganglia thalamocortical projections.

Psychoendocrine model of depression

Abstract (1) Hypothalamo-pituitary dysfunction appears to be the most significant finding of neuroendocrine studies of depression. (2) The underlying pathology of this dysfunction is probably a metabolic disturbance of brain monoamines. (3) Brain monoamines were examined by the fluorescence histochemical method in a stress-induced animal model of depression. (4) An increase in fluorescence intensity was found in the cell groups of the ascending NA system. (5) Cell bodies and nerve terminals of the tubero-infundibular DA system showed a decrease of fluorescence intensity. (6) The turnover rate of catecholamines in nerve terminals of the ascending NA system decreased.