Zsolt Csaba

Growth hormone-releasing hormone, somatostatin, galanin and β-endorphin afferents to the hypothalamic periventricular nucleus

A combined retrograde tracing (wheat germ agglutinin-horseradish peroxidase-gold complex)-immunohistochemical technique was used to identify the origin of growth hormone-releasing hormone (GHRH)-immunoreactive (ir), beta-endorphin-ir, galanin (GAL)-ir and somatostatin (SRIH)-ir terminals in the hypothalamic periventricular nucleus, which contains all the hypophysiotrophic SRIH-ir neurons. Retrogradely labeled cells were mostly observed ipsilaterally in the arcuate, dorsomedial (DMH), suprachiasmatic nuclei and the parvocellular part of the paraventricular nucleus. They were less abundant in the ventromedial and periventricular nuclei and in the lateral hypothalamus. The proportion of retrogradely labeled GHRH cells was greater at the outer rim of the ventromedial nucleus (10%) than in the arcuate nucleus proper (3%). In the arcuate nucleus, 14% of the SRIH-ir cells projected to the periventricular nucleus. Of the GAL-ir cells in the arcuate and the DMH 10% were double-labeled. Scattered retrogradely labeled GAL-ir cells were observed in paraventricular and perifornical nuclei and in the lateral hypothalamus. Of the beta-Endorphin-ir cells in the ventral part of the arcuate nucleus 15% were retrogradely labeled. It is concluded that: (1) There is no major direct connection between the hypophysiotropic GHRH and SRIH neurons, respectively, located in the arcuate and periventricular nucleus. (2) GHRH projections to the periventricular nucleus arise mainly from cells located at the outer rim of the ventromedial nucleus. (3) Intrahypothalamic SRIH projections to the periventricular nucleus arise from arcuate SRIH neurons located along the wall of the third ventricle. (4) GAL neurons from the DMH and the arcuate nucleus innervate to the same extent the periventricular nucleus. (5) beta-Endorphin arcuate neurons strongly innervate the periventricular nucleus.

Somatostatin Receptor Type 2 Undergoes Plastic Changes in the Human Epileptic Dentate Gyrus

Temporal lobe epilepsy (TLE) is characterized by hippocampal sclerosis together with profound losses and phenotypic changes of different classes of interneurons, including those expressing somatostatin (SRIF). To understand the functional significance of the plasticity of SRIF transmission in TLE, unraveling the status of SRIF receptors is, however, a prerequisite. To address this issue, we characterized expression and distribution of the major SRIF receptor, the sst2 subtype, in hippocampal tissue resected in patients with TLE using complementary neuroanatomic approaches. In patients with hippocampal sclerosis, the number of cells expressing sst2 receptor mRNA as well as sst2 receptor-binding sites and immunoreactivity decreased significantly in the CA1-3, reflecting neuronal loss. By contrast, in the dentate gyrus, sst2 receptor mRNA expression was strongly increased in the granule cell layer, and sst2 receptor-binding sites and immunoreactivity was preserved in the inner but decreased significantly in the outer molecular layer. In this latter region, pronounced changes in SRIF terminal fields were observed. Decreased receptor density in the distal dendrites of granule cells is likely to reflect downregulation of sst2 receptors in response to physiopathologic release of SRIF. Because sst2 receptors have anticonvulsant and antiepileptogenic properties, this phenomenon may contribute to the etiology of TLE seizures.

Synaptic contacts of vesicular glutamate transporter 2 fibres on chemically identified neurons of the hypothalamic suprachiasmatic nucleus of the rat

The hypothalamic suprachiasmatic nucleus (SCN), which plays a pivotal role in the control of circadian rhythms, consists of several neuronal subpopulations characterized by different neuroactive substances. This prominent cell group has a fairly rich glutamatergic innervation, but the cell types that are targeted by this innervation are unknown. Therefore, the purpose of the present study was to examine the relationship between the afferent glutamatergic axon terminals and the vasoactive intestinal polypeptide (VIP)‐, arginine‐vasopressin (AVP)‐ and γ‐aminobutyric acid (GABA)‐positive neurons of the SCN. Glutamatergic elements were revealed via immunocytochemical double‐labelling for vesicular glutamate transporter type 1 (VGluT1) and type 2 (VGluT2), and brain sections were imaged via confocal laser‐scanning microscopy and electron microscopy. Numerous VGluT2‐immunoreactive axons were observed to be in synaptic contact with VIP‐ and GABA‐positive neurons, and only a few synapses were detected between VGluT2 boutons and AVP neurons. VGluT1 axon terminals exhibiting very moderate distribution in this cell group were observed to be in synaptic contact with chemically unidentified neurons. The findings provide the first morphological data on the termination of presumed glutamatergic fibres on chemically identified neurons of the rat SCN, and indicate that all three prominent cell types of the cell group receive glutamatergic afferents.

Lesion of the insular cortex affects luteinizing hormone and testosterone secretion of rat - Lateralized effect

The possible involvement of the insular cortex in the neural control of the hypophyseal-testicular axis was studied in male rats. Right- but not left-sided lesion of the insular cortex resulted in a significant decrease in basal testosterone secretion in vitro and serum testosterone concentration. Both right- and left-sided lesions of the insular cortex induced significant increase in serum luteinizing hormone (LH) concentration. Unilateral lesion of the insular cortex on either sides had no effect on serum follicle stimulating hormone (FSH) level. The results indicate that the insular cortex is involved in the control of testosterone and LH secretion. The data further suggest that the right insular cortex plays a predominant role in the control of male endocrine reproductive processes.

Lesion of the amygdala on the right and left side suppresses testosterone secretion but only left-sided intervention decreases serum luteinizing hormone level

The effect of right- and left-sided intra- amygdaloid injection of kainic acid on the hypothalamo- hypophyseal-testicular axis was studied in rats. Both right- and left-sided injection of the neurotoxin into the amygdala resulted in a significant decrease in basal testosterone secretion in vitro of both testes and in serum testosterone concentration. In addition, left-sided administration of kainic acid significantly suppressed serum luteinizing hormone level, while right-sided intervention did not alter this parameter. The results of the present study provide further evidence on the involvement of the amygdala in the control of testicular steroidogenesis. Furthermore, the observations suggest functional asymmetry of the amygdala concerning the mechanism of suppressed testosterone secretion.

Effect of unilateral deafferentation in the medial basal portion of the temporal lobe on the hypophyseo-ovarian axis in rats: an age-dependent lateralized control mechanism

The possible physiological role of the medial basal portion of the temporal lobe (including the corticomedial amygdaloid nucleus) in the neural control of the hypophyseo-ovarian axis was studied in pre- and postpubertal as well as in adult rats. Unilateral deafferentiation of a small medio-basal portion of the temporal lobe was performed in unilaterally ovariectomized animals, and the rate of compensatory hypertrophy of the remaining ovary was recorded. In adults compensatory ovarian hypertrophy was significantly reduced following right- but not left-sided deafferentiation. Temporal lobe surgery did not significantly influence the usual compensatory ovarian growth in pre- and postpubertal rats. Serum luteinizing hormone levels decreased significantly in adults regardless of the side of brain interventions, while no obvious change in the hormone concentration could be observed in prepubertals. Serum follicle-stimulating hormone concentrations showed no alterations in any experimental group. In postpubertal rats the serum progesterone level was unchanged following brain surgery. The present observations indicate that unilateral deafferentation in the temporal lobe could modify compensatory ovarian hypertrophy by a direct neural mechanism and data further suggest functional laterality of these structures in the control of ovarian functions.

Testicular injection of 5,6-dihydroxytryptamine or vasectomy interferes with the local stimulatory effect of oxytocin on testicular steroidogenesis in immature rats

Previous studies indicated that in immature rats testicular administration of oxytocin stimulates testicular steroidogenesis. In the present study, testicular treatment with oxytocin (50 ng) was combined with pharmacological or surgical denervation of the testis in hemigonadectomized immature rats. For denervation 5,6-dihydroxytryptamine (160 micrograms/testis), a substance that destroys serotoninergic neuronal elements, was injected intratesticularly or vasectomy was performed, which also includes transection of the inferior testicular nerve. In 9-day-old animals both vasectomy and pretreatment of the testis with 5,6-dihydroxytryptamine prevented the oxytocin-induced rise in serum testosterone concentration. In addition, intratesticular injection of oxytocin combined with vasectomy resulted in a significant increase in in vitro basal testosterone secretion of the testis. A similar effect was not observed in the 5,6-dihydroxytryptamine-pretreated group receiving oxytocin. The results indicate that testicular innervation is involved in the control of local peptide effects, and data further suggest a differential role of these neural elements in intratesticular regulatory processes.

Effect of intratesticular administration of TRH or anti-TRH antiserum on function of rat testis.

The effect of intratesticular administration of thyrotropin-releasing hormone (TRH) and anti-TRH antiserum on steroidogenesis was studied in immature and adult rats. In 9-day-old animals local administration of the neuropeptide resulted in an increase in basal testosterone secretion in vitro. Similar treatment of 15-day-old rats suppressed hCG-stimulated testosterone secretion with no change in basal testosterone production. In both immature groups the treatment did not affect serum testosterone concentration. By contrast, in adults TRH decreased serum testosterone level, but did not influence basal and hCG-stimulated testosterone secretion. Both in immature and adult rats, the changes in steroidogenesis were evident 1 hour posttreatment. Five days after the administration of anti-TRH antiserum into the remaining testis of immature rats subjected to hemicastration just prior to the antiserum treatment, the alterations in steroidogenesis were opposite to those detected after treatment with TRH. In 9-day-old rats the antiserum suppressed steroidogenesis, while in 15-day-old animals it stimulated testosterone secretion. The results suggest that testicular TRH might exert a local action on testicular steroidogenesis, and the effect is age-dependent.