What may be the anatomical basis that secretin can improve the mental functions in autism?

Autism was first described and characterized as a behavioral disorder more than 50 years ago. The major abnormality in the central nervous system is a cerebellar atrophy. The characteristic histological sign is a striking loss or abnormal development in the Purkinje cell count. Abnormalities were also found in the limbic system, in the parietal and frontal cortex, and in the brain stem. The relation between secretin and autism was observed 3 years ago. Clinical observations by Horváth et al. [J. Assoc. Acad. Minor. Physicians 9 (1998) 9] supposed a defect in the role of secretin and its receptors in autism. The aim of the present work was to study the precise localization of secretin immunoreactivity in the nervous system using an immunohistochemical approach. No secretin immunoreactivity was observed in the forebrain structures. In the brain stem, secretin immunoreactivity was observed in the mesencephalic nucleus of the trigeminal nerve, in the superior olivary nucleus, and in scattered cells of the reticular formation. The most intensive secretin immunoreactivity was observed in the Purkinje cells of the whole cerebellum and in some of the neurons of the central cerebellar nuclei. Secretin immunoreactivity was also observed in a subpopulation of neurons in the primary sensory ganglia. This work is the first immunohistochemical demonstration of secretin-immunoreactive elements in the brain stem and in primary sensory ganglia.

Comparative study on the appearance of various bioactive peptides in foregut derivates during the ontogenesis.

Bioactive peptides have an important multifunctional role in the gastrointestinal tract. In the present study we have investigated the dynamism of the appearance of PACAP (pituitary adenylate cyclase activating polypeptide), VIP (vasoactive intestinal polypeptide), gastrin, and secretin immunoreactivities in human foregut derivates during the ontogenesis using an immunohistochemical approach. None of these peptides were observed in the foregut derivates of an 8-week-old embryo. VIP immunoreactive nerve fibers appeared by the 11th week in the smooth muscle layers of the stomach. No other peptide immunoreactivities were observed of this stage. In 18- and 20-week old fetuses PACAP, secretin, and gastrin immunoreactive cells appeared in the developing glands of the stomach. In the duodenum gastrin immunoreactivity was present in the Lieberkühn's glands and secretin immunoreactive cells were seen between the surface epithelial cells. In the pancreas secretin immunoreactivity was found in the Langerhans islets; however, PACAP immunreactivity was observed in the exocrine portion. The distribution of VIP fibers did not change during the fetal life and it was similar to the adult pattern. According to our results the appearance of PACAP, secretin, and gastrin in the developing glands suggests their role in the proliferation and differentiation of the epithelial derivates.

Distribution of pituitary adenylate cyclase activating polypeptide (PACAP) immunoreactive elements in the brain stem of rats studied by immunohistochemistry.

In the present work the distribution of pituitary adenylate cyclase activating polypeptide (PACAP) immunoreactive elements in rat brain stem were described using immunohistochemistry. The following structures were PACAP immunoreactive: 1. The dorsomedial and ventrolateral cell columns of the motor nuclei of cranial nerves. 2. Primary somatosensory cells in the mesencephalic nucleus of the trigeminal nerve and central axons of the branchial cranial nerves in the spinal trigeminal tract. 3. Visceral afferent fibers in the solitary tract and cell bodies in the dorsal motor nucleus of the vagus. 4. Second and third order sensory neurons of the cochlear and vestibular systems. 5. Scattered fibers in various regions of the brain stem and well-defined fiber bundles in the interpeduncular area. 6. Cell bodies in the red nucleus, substantia niga, in some cell groups of the reticular formation and in the raphe nuclei, as well as in the pontine dorsolateral tegmentum.

VIP fibers in rat optic chiasm and optic nerve arising from the hypothalamus.

This is the first report showing VIP fibers in the optic chiasm and the optic nerves of intact rats. These fibers form a fan-shaped dorso-medial bundle in the optic nerves. After colchicine injection into the vitreous body VIP fibers could be followed farther in the optic nerve toward the eye when compared to intact rats. After removal of eyes (enucleation) the VIP fiber-bundle became more prominent and VIP immunoreactive perikarya appeared in the supraoptic and para ventricular nuclei. When five-nine months after the enucleation Phaseolus vulgaris leucoagglutinin was administered to the paraventricular or supraoptic area, the anterogradely transported tracer was demonstrated in the optic nerve. These observations suggest the existence of a hypothalamic projection to the eye, which is, at least in part, VIP immunoreactive.

Present status of knowledge about the distribution and colocalization of PACAP in the forebrain.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a recently discovered member of the secretion family. 1. PACAP is a well conserved peptide during the phylogenesis. It has two bioactive amidated forms: PACAP38 and PACAP27 with 38 and 27 residues, respectively. 2. PACAP and its receptors are widely distributed in the central and peripheral nervous systems and in non-neural tissues. 3. In the central nervous system PACAP immunoreactive neuronal elements have been observed in the hypothalamus (magno- and parvocellular cell groups), both layers of the median eminence, the septum, the thalamus, the amygdaloid complex, the hippocampus, and various regions of the cortex. 4. In the periphery, PACAP was found in small sensory and parasympathetic neurons. 5. In the hypothalamus PACAP partially colocalizes with oxytocin- and tyrosine hydroxylase-immunoreactivities. In the septum there is no colocalization between the two immunoreactivities, but PACAP- and tyrosine hydroxylase-immunoreactive fibers were often found to establish synaptic contacts with the same, unlabeled dendrite. It was reported that in the periphery, in sensory neurons PACAP colocalized with substance-P and in parasympathetic neurons with acetylcholin. 6. PACAP functions as a neurotransmitter, hypothalamic releasing factor, posterior pituitary hormone, and trophic factor of the nervous tissue. PACAP also participates in neuro-immunoendocrine mechanisms.

Arrangement of neurons in the medullary reticular formation and raphe nuclei projecting to thoracic, lumbar and sacral segments of the spinal cord in the cat.

The distribution of neurons in the medullary reticular formation and raphe nuclei projecting to thoracic, lumbar and sacral spinal segments was studied, using the technique of retrograde transport of horseradish peroxidase (HRP), alone or in combination with nuclear yellow (NY). Retrogradely labeled cells were observed in the lateral tegmental field (FTL), paramedian reticular nucleus, magnocellular reticular nucleus (Mc), in the gigantocellular nucleus (Gc), lateral reticular nucleus (LR), lateral paragigantocellular nucleus (PGL), rostral ventrolateral medullary reticular formation (RVR), as well as in the medullary raphe nuclei following the injection of the tracer substance(s) into various levels of the spinal cord. The FTL, the ventral portion of the paramedian reticular nucleus (PRv), Mc, LR, PGL and the raphe nuclei were found to project to thoracic, lumbar and sacral spinal segments. This projection was bilateral; the contralaterally projecting fibers crossed the midline at or near their termination site. The dorsal portion of the paramedian reticular nucleus (PRd), Gc and the RVR projected mainly to thoracic segments. This projection was unilateral. Experiments in which the HRP-injection was combined with lesion of the spinal cord showed that some descending raphe-spinal axons coursed presumably alongside the central canal. Experiments with two tracer substances suggested that some reticulo- and raphe-spinal neurons had axon collaterals terminating both in thoracic and sacral spinal segments.

Distribution of hypothalamic neurons projecting to the thoracic and sacral spinal segments in the cat.

The distribution of hypothalamic neurons participating in hypothalamo-spinal projections (hypothalamo-spinal HSP neurons) to the thoracic and sacral segments was studied using the technique of retrograde axonal transport. Horseradish peroxidase (HRP) and nuclear yellow (NY) were injected into various thoracic and/or sacral spinal cord segments. The retrogradely labeled cells were distributed in a continuous crescent-shaped field in the posterior, dorsolateral and lateral regions of the hypothalamus: starting from the ventral tegmental area (VTA), through the posterior hypothalamic nucleus (PH), the supramammillary nucleus (SM), the dorsal- and lateral hypothalamic area (AH1) and LH), the dorsomedial nucleus (DM) as well as in the paraventricular nucleus (PV). Neurons in all of the above hypothalamic nuclei project as caudally as to the sacral segments. The projection is bilateral and the contralaterally projecting fibres cross the midline at or near their termination site. Projection to thoracic segments is mainly ipsilateral. HSP neurons projecting to upper thoracic and sacral segments showed different patterns of distribution. A sacral injection resulted in most labeled neurons in the SM and LH and less labeled neurons in the PV, than a thoracic injection of comparable size and locations. Experiments with two tracer substances suggested that some of HSP neurons had divergent axon collaterals terminating both in thoracic and sacral spinal segments.

Distribution of neurons in the lateral pontine tegmentum projecting to thoracic, lumbar and sacral spinal segments in the cat.

The course of descending fibers projecting to the spinal cord and the arrangement of their parent cells located in various nuclei of the dorso-lateral pontine tegmentum were studied using the horseradish peroxidase (HRP) retrograde axonal transport technique. Retrogradely labeled neurons were found in the locus coeruleus (LC), subcoeruleus (SC), Kölliker-Fuse nucleus (KF) and in the lateral parabrachial nucleus (LPB) after HRP injections into various spinal segments. Neurons innervating the thoracic spinal cord were found to be arranged in the ventral portion of the LC and in the entire SC; their axons descended ipsilaterally. Neurons with descending axons to lumbar segments were seen mainly in the ventral portion of the LC and in the medial portion of SC. Most of their axons were also seen to descend ipsilaterally. Neurons projecting to sacral segments occurred in the entire LC and in the medial portion of the SC. Large part of descending fibers crossed the midline at the level of (or near) the termination site. Neurons of all portions of the KF and LPB projected to the thoracic spinal cord only ipsilaterally, while many descending fibers innervating the sacral segments crossed the midline.

Lamellar arrangement of neuronal somata in the dorsal root ganglion of the cat.

The retrograde transport of horseradish peroxidase (HRP) was used to study the distribution of perikarya in the dorsal root ganglia (DRGs). Injections of HRP subcutaneously into a small area of the foreleg, flank, perineum, the central pad of the forepaw, muscles of the foreleg, the wall of the urinary bladder, and mucosa of the rectum resulted in many retrogradely labeled perikarya in one DRG. Labeled perikarya were distributed in the ganglia proximally to distal elongated slabs or columns, especially in cases of subcutaneous injections. A similar slab, or columnar distribution, of HRP-labeled perikarya was noticed when the tracer was injected into the spinal cord preceded by the transection of all dorsal root filaments but one. Perikarya located along the lateral border of the ganglion were labeled through rostral filaments, and perikarya distributed along the medial border were labeled through caudal filaments. A segmental somatotopic map has been conceived for the DRG as an intermediate territory between the periphery and the spinal cord.

Sensitivity of the short-range spinal interneurons of the cat to experimental spinal cord trauma.

The technique of retrograde axoplasmic transport was used to demonstrate the effect of experimental spinal cord injury on the spinal interneurons in the upper lumbar and lower thoracic segments of cats. Force of varied intensity was applied to the dorsal surface of the spinal cord and horseradish peroxidase (HRP) was injected into the next caudal segment. A large impact (250 to 350 gm-cm) inducing permanent paraplegia of the hind legs blocked the axoplasmic transport instantaneously in both cranial and caudal directions. If 1 week elapsed between the trauma and injection, neurons cranial to the trauma did not show any evidence for retrograde axoplasmic transport, while few neurons in the caudal direction were labeled with HRP. A moderate impact (150 gm-cm) which rendered the animals only transiently paraplegic spared the axoplasmic transport in some neurons both cranially and caudally to the injection. No obvious recovery or additional loss in the number of HRP-labeled neurons could be found in the cats if the injections followed the trauma by 1 week. The loss of spinal cord neurons following the injury seems to be the immediate mechanical consequence of the trauma.

Descending course of primary afferent collaterals in the cat's spinal cord.

After injecting horseradish-peroxidase into the lower thoracic, lumbar and sacral spinal cord segments of cats, labelled perikarya were found in several spinal ganglia localized cranially to the site of injection. The segmental distance between the injection site and the rostralmost localized ganglion with labelled cells varied depending on the medio-lateral localization of the injection. The longest distance (10 segments) was achieved by medial injections. Primary sensory neurones with long descending collaterals belong to large ganglion cells.