No abstract

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are among the human synucleinopathies, which share the neuropathological features of alpha-synuclein immunoreactive neuronal and/or glial aggregations, as well as progressive neuronal loss in select brain regions (e.g. dopaminergic substantia nigra and ventral tegmental area, cholinergic pedunculopontine nucleus). Despite a number of studies about brainstem pathologies in PD and DLB, there is currently no detailed information available regarding the presence of alpha-synuclein immunoreactive inclusions (a) in the cranial nerve, precerebellar, vestibular and oculomotor brainstem nuclei and (b) in brainstem fiber tracts and oligodendroctyes. Therefore, we performed a detailed analysis of the alpha-synuclein immunoreactive inclusion pathologies in the brainstem nuclei (Lewy bodies, LB; Lewy neurites, LN; coiled bodies, CB) and fiber tracts (LN, CB) of clinically diagnosed and neuropathologically confirmed PD and DLB patients. As also reported in previous studies, LB and LN were most prevalent in the substantia nigra, ventral tegmental area, pedunculopontine and raphe nuclei, periaqueductal gray, locus coeruleus, parabrachial nuclei, reticular formation, prepositus hypoglossal, dorsal motor vagal, and solitary nuclei. However, we for the first time demonstrated LB and LN in all cranial nerve nuclei, premotor oculomotor, precerebellar and vestibular brainstem nuclei, as well as LN in all brainstem fiber tracts. CB were present in nearly all brainstem nuclei and brainstem fiber tracts containing LB and/or LN. These novel brainstem findings can account for or contribute to a large variety of less well-explained PD and DLB symptoms (e.g. gait and postural instability, impaired balance and postural reflexes, falls, ingestive and oculomotor dysfunctions), and point to the occurrence of disturbances of intra-axonal transport processes and a transneuronal spread of the underlying pathological processes of PD and DLB along anatomical pathways in a prion-like manner.

Bone morphogenetic proteins (BMPs) induce autonomic neurogenesis in neural crest cultures and stimulate sympathetic neuron development when overexpressed in vivo. We demonstrate that inhibition of BMPs in the chick embryo bythe BMP antagonist Noggin prevents sympathetic neuron generation. In Noggin-treated embryos, the noradrenergic marker genes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), panneuronal neurofilament 160 (NF160) and SCG10 genes, and the transcriptional regulators Phox2b and Phox2a are not expressed in sympathetic ganglia. Whereas initial ganglion development is not affected, the expression of the basic helix-loop-helix transcription factor Cash-1 is strongly reduced. These results demonstrate that BMPs are essential for sympathetic neuron development and establish Cash-1 and Phox2 genes as downstream effectors of BMPs in this lineage.

Amphioxus neuroanatomy is important not just in its own right but also for the insights it provides regarding the evolutionary origin and basic organization of the vertebrate nervous system. This review summarizes the overall layout of the central nervous system (CNS), peripheral nerves, and nerve plexuses in amphioxus, and what is currently known of their histology and cell types, with special attention to new information on the anterior nerve cord. The intercalated region (IR) is of special functional and evolutionary interest. It extends caudally to the end of somite 4, traditionally considered the limit of the brain-like region of the amphioxus CNS, and is notable for the presence of a number of migrated cell groups. Unlike most other neurons in the cord, these migrated cells detach from the ventricular lumen and move into the adjacent neuropile, much as developing neurons do in vertebrates. The larval nervous system is also considered, as there is a wealth of new data on the organization and cell types of the anterior nerve cord in young larvae, based on detailed electron microscopical analyses and nerve tracing studies, and an emerging consensus regarding how this region relates to the vertebrate brain. Much less is known about the intervening period of the life history, i.e., the period between the young larva and the adult, but a great deal of neural development must occur during this time to generate a fully mature nervous system. It is especially interesting that the vertebrate counterparts of at least some postembryonic events of amphioxus neurogenesis occur, in vertebrates, in the embryo. The implication is that the whole of the postembryonic phase of neural development in amphioxus needs to be considered when making phylogenetic comparisons. Yet this is a period about which almost nothing is known. Considering this, plus the number of new molecular and immunocytochemical techniques now available to researchers, there is no shortage of worthwhile research topics using amphioxus, of whatever stage, as a subject.

Implant loading might have stimulated increased bone formation and thus may be a key factor in influencing positive osseointegration. In addition, immediately loaded implants may osseointegrate in a similar manner as delayed loaded implants.

Injections of the carbocyanine dye, DiI, into the lateral pallium of the silver lamprey reveal that this pallial region receives bilateral inputs from the olfactory bulbs, dorsomedial telencephalic neuropil, and the habenular nuclei, and ipsilateral inputs from the septum, preoptic area, medial pallium, thalamus, and, possibly, the striatum. The efferent projections of the lateral pallium form dorsal (olfacto-habenular tract of Heier) and ventral (olfacto-thalamic and hypothalamic tracts of Heier) bundles. The dorsal bundle terminates ipsilaterally in the dorsal pallium, medial pallium, habenular nuclei, and pretectum and contralaterally in the habenular nuclei and, possibly, the dorsal pallium. The ventral bundle terminates ipsilaterally in the septum, striatum, and preoptic areas and bilaterally within the hypothalamus. Injections of DiI into the medial pallium reveal bilateral inputs to this pallial formation from the olfactory bulbs, the dorsomedial telencephalic neuropil, septum, habenular nuclei, thalamic nuclei, preoptic area and hypothalamus, as well as ipsilateral inputs from the lateral pallium, dorsal isthmal grey and midbrain tegmentum. The efferent projections of the medial pallium form dorsal, ventral and descending bundles. The dorsal bundle terminates ipsilaterally in the dorsal and lateral pallia and in the olfactory bulb. The ventral bundle terminates ipsilaterally in the dorsal pallium and bilaterally within the lateral pallium and in preoptic and hypothalamic areas. The descending bundle terminates bilaterally in thalamic and hypothalamic areas and in the pretectum and optic tectum. These data support a number of earlier hypotheses concerning pallial homologues in lampreys and other vertebrates but suggest that the earlier hypothesis of an olfactory origin of the telencephalon of craniates should be rejected.

No abstract

SUMMARY Knowledge about intracellular signal transduction cascades is largely based on investigations of cultured cells whose responses to different stimuli are typically quantified via RIA, ELISA, or immunoblots. These techniques, which require relatively large amounts of biological material, are performed with homogenized cells and therefore do not allow localization of the molecules under investigation. We describe a protocol for recording dose-response curves directly from immunocytochemical preparations using rat pinealocytes as a model system. The cells were exposed to ␤-adrenergic stimuli inducing the phosphorylation of the transcription factor CREB (mediated by PKA), an increase in ICER protein levels, and synthesis and release of melatonin. Melatonin concentrations were determined by ELISA. cPKA, phosphorylated CREB, and ICER were demonstrated by immunocytochemistry and immunoblots. Dose-response curves were recorded by measuring the integrated density of the immunoreactive sites with an image analysis program. Dose-response curves from immunoblots and immunocytochemical preparations showed almost identical dynamics, validating the immunocytochemical approach, which minimizes the amount of biological material needed for such studies, allows combined quantification and localization of biomolecules, and may even be more sensitive than immunoblotting.