Neurogenesis in the central olfactory pathway of adult decapod crustaceans: development of the neurogenic niche in the brains of procambarid crayfish

<p>Abstract</p> <p>Background</p> <p>In the decapod crustacean brain, neurogenesis persists throughout the animal's life. After embryogenesis, the central olfactory pathway integrates newborn olfactory local and projection interneurons that replace old neurons or expand the existing population. In crayfish, these neurons are the descendants of precursor cells residing in a neurogenic niche. In this paper, the development of the niche was documented by monitoring proliferating cells with S-phase-specific markers combined with immunohistochemical, dye-injection and pulse-chase experiments.</p> <p>Results</p> <p>Between the end of embryogenesis and throughout the first post-embryonic stage (POI), a defined transverse band of mitotically active cells (which we will term 'the deutocerebral proliferative system' (DPS) appears. Just prior to hatching and in parallel with the formation of the DPS, the anlagen of the niche appears, closely associated with the vasculature. When the hatchling molts to the second post-embryonic stage (POII), the DPS differentiates into the lateral (LPZ) and medial (MPZ) proliferative zones. The LPZ and MPZ are characterized by a high number of mitotically active cells from the beginning of post-embryonic life; in contrast, the developing niche contains only very few dividing cells, a characteristic that persists in the adult organism.</p> <p>Conclusions</p> <p>Our data suggest that the LPZ and MPZ are largely responsible for the production of new neurons in the early post-embryonic stages, and that the neurogenic niche in the beginning plays a subordinate role. However, as the neuroblasts in the proliferation zones disappear during early post-embryonic life, the neuronal precursors in the niche gradually become the dominant and only mechanism for the generation of new neurons in the adult brain.</p

Adult Neurogenesis: Ultrastructure of a Neurogenic Niche and Neurovascular Relationships

The first-generation precursors producing adult-born neurons in the crayfish (Procambarus clarkii) brain reside in a specialized niche located on the ventral surface of the brain. In the present work, we have explored the organization and ultrastructure of this neurogenic niche, using light-level, confocal and electron microscopic approaches. Our goals were to define characteristics of the niche microenvironment, examine the morphological relationships between the niche and the vasculature and observe specializations at the boundary between the vascular cavity located centrally in the niche. Our results show that the niche is almost fully encapsulated by blood vessels, and that cells in the vasculature come into contact with the niche. This analysis also characterizes the ultrastructure of the cell types in the niche. The Type I niche cells are by far the most numerous, and are the only cell type present superficially in the most ventral cell layers of the niche. More dorsally, Type I cells are intermingled with Types II, III and IV cells, which are observed far less frequently. Type I cells have microvilli on their apical cell surfaces facing the vascular cavity, as well as junctional complexes between adjacent cells, suggesting a role in regulating transport from the blood into the niche cells. These studies demonstrate a close relationship between the neurogenic niche and vascular system in P. clarkii. Furthermore, the specializations of niche cells contacting the vascular cavity are also typical of the interface between the blood/cerebrospinal fluid (CSF)-brain barriers of vertebrates, including cells of the subventricular zone (SVZ) producing new olfactory interneurons in mammals. These data indicate that tissues involved in producing adult-born neurons in the crayfish brain use strategies that may reflect fundamental mechanisms preserved in an evolutionarily broad range of species, as proposed previously. The studies described here extend our understanding of neurovascular relationships in the brain of P. clarkii by characterizing the organization and ultrastructure of the neurogenic niche and associated vascular tissues

Histone Deacetylase (HDAC) Inhibitors as Potential Drugs to Target Memory and Adult Hippocampal Neurogenesis

Epigenetic mechanisms have been recognized to be important for the physiologic regulation of cognitive functions and their pathologic alterations contribute to many neurologic and neuropsychiatric diseases. We survey here an important mechanism of epigenetic regulation of brain function, the histone acetylation state modulated by histone deacetylases (HDACs), and its impact on cognitive behaviour as well as on hippocampal adult neurogenesis, which is presently recognized as an essential process for learning and memory. A potent way to modulate histone acetylation state is through HDAC inhibitors, which are currently tested as potential drugs for treatment of major diseases including cancer and neurologic/neuropsychiatric disorders. Various HDAC inhibitor molecules and their impact on brain function are examined with particular reference to neuroprotective action of some of these substances. The core of the review deals with the current status of the literature on the use of some of these inhibitors as memory enhancers and dementia-fighting agents as well as on their possible role in regulation of adult neurogenesis in the hippocampal dentate gyrus, a process linked to the ability of acquiring new memories. Possible reasons for the many controversial results arising from the literature are discussed in view of establishing a more reliable ground for the future use of HDAC inhibitors to improve memory process in brain health and disease

Chronic valproic acid administration impairs contextual memory and dysregulates hippocampal GSK-3\u3b2 in rats.

Valproic acid (VPA), a long-standing anti-epileptic and anti-manic drug, exerts multiple actions in the nervous system through various molecular mechanisms. Neuroprotective properties have been attributed to VPA in different models of neurodegeneration, but contrasting results on its improvement of learning and memory have been reported in non-pathologic conditions. In the present study, we have tested on a hippocampal-dependent learning test, the contextual fear conditioning, the effect of chronic VPA administration through alimentary supplementation that allows relatively steady concentrations to be reached by a drug otherwise very rapidly eliminated in rodents. Contextual fear memory was significantly impaired in rats chronically treated with VPA for 4. weeks. To understand the cellular and molecular correlates of this amnesic effect with particular regard to hippocampus, we addressed three putatively memory-related targets of VPA action in this brain area, obtaining the following main results: i) chronic VPA promoted an increase of post-translational modifications of histone H3 (acetylation and phosphorylation) known to favor gene transcription; ii) adult neurogenesis in the dentate gyrus, which has been controversially reported to be affected by VPA, was unchanged; and iii) GSK-3\u3b2, a kinase playing a key role in hippocampal plasticity, as well as in learning and memory, was dysregulated by VPA treatment. These results point at GSK-3\u3b2 dysregulation in the hippocampus as an important parameter in the amnesic effect of VPA. The VPA amnesic effect in the animal model here reported is also supported by some observations in patients and, therefore, it should be taken into account and monitored in VPA-based therapies