Neurochemical and cellular specializations in the mammalian neocortex reflect phylogenetic relationships: evidence from primates, cetaceans, and artiodactyls

Most of the available data on the cytoarchitecture of the cerebral cortex in mammals rely on Nissl, Golgi, and myelin stains and few studies have explored the differential morphologic and neurochemical phenotypes of neuronal populations. In addition, the majority of studies addressing the distribution and morphology of identified neuronal subtypes have been performed in common laboratory animals such as the rat, mouse, cat, and macaque monkey, as well as in postmortem analyses in humans. Several neuronal markers, such as neurotransmitters or structural proteins, display a restricted cellular distribution in the mammalian brain, and recently, certain cytoskeletal proteins and calcium-binding proteins have emerged as reliable markers for morphologically distinct subpopulations of neurons in a large number of mammalian species. In this article, we review the morphologic characteristics and distribution of three calcium-binding proteins, parvalbumin, calbindin, and calretinin, and of the neurofilament protein triplet, a component of the neuronal cytoskeleton, to provide an overview of the presence and cellular typology of these proteins in the neocortex of various mammalian taxa. Considering the remarkable diversity in gross morphological patterns and neuronal organization that occurred during the evolution of mammalian neocortex, the distribution of these neurochemical markers may help define taxon-specific patterns. In turn, such patterns can be used as reliable phylogenetic traits to assess the degree to which neurochemical specialization of neurons, as well as their regional and laminar distribution in the neocortex, represent derived or ancestral features, and differ in certain taxa from the laboratory species that are most commonly studied.     

Nodal and paranodal structural changes in mouse and rat optic nerve during Wallerian degeneration

Ultrastructural changes in nodal and paranodal regions of myelinated mouse and rat optic nerve fibers were followed between 4 h and 28 days during the course of Wallerian degeneration. In the mouse, axoplasmic changes, including accumulation of organelles and segregation of microtubules, were detectable 4 h after transection, and progressed to a maximum level on day 4, at which time many axons were markedly swollen. Dense axoplasm was seen as early as 16 h and was a common feature of degenerating axoplasm at later times. Paranodal changes, which first appeared as early as 16 h after injury, included detachment of terminal loops of myelin from the axolemma, disconnection of terminal loops from compact myelin lamellae and broadening of terminal loops, or separation of the loops from each other, resulting in paranodal elongation. In freeze-fracture replicas, the E-face of the axolemma showed the normal particle distribution as late as days 3-5. By day 8, however, the nodal particles were patchy and the overall nodal particle density was reduced to approximately half normal. Some normal-looking fibers were present at all stages examined, but their number had declined to about half the total population on day 5 and to less than 10% on day 11. In the rat, the overall sequence of events and time course were comparable to those in the mouse. Thus, the morphological changes found follow approximately the same sequence as that described previously in frog nerves, but progress more rapidly in the mouse and rat.     

Distribution of substance P and neurokinin-1 receptor immunoreactivity in the suprachiasmatic nuclei and intergeniculate leaflet of hamster, mouse, and rat

The circadian pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) receives photic information directly via the retinohypothalamic tract (RHT) and indirectly from retinally innervated cells in the thalamic intergeniculate leaflet (IGL) that project to the SCN. Using standard immunohistochemical methods, we examined the presence and distribution of substance P (SP) and the neurokinin-1 receptor (NK-1) in the SCN and IGL of rat and determined whether the patterns of immunostaining generalized to the SCN and IGL of Syrian hamster, Siberian hamster, and mouse. Terminals immunoreactive for SP were sparse within the SCN of Siberian and Syrian hamsters and mouse but were intense in the ventral, retinally innervated portion of the rat SCN. Immunostaining for the NK-1 receptor was mainly absent from the SCN of hamster and mouse. In contrast, a plexus of NK-1-ir cells and processes that was in close proximity to SP-ir terminals was found in the ventral SCN of the rat. Substance P-ir terminals were observed in the IGL of all four species, as were NK-1-ir cells and fibres. Double-labelled IGL sections of hamster or rat revealed SP-ir terminals in close apposition to NK-1-immunostained cells and/or fibres. These data indicate that SP could be a neurotransmitter of the RHT in rat, but not in hamster or in mouse, and they highlight potential species differences in the role of SP within the SCN circadian pacemaker. Such species differences do not appear to exist at the level of the IGL, where SP-ir and NK-1-ir were similar in all species studied.     

Congenital fiber type disproportion myopathy in Lowe syndrome

Two brothers with the typical clinical features of oculo-cerebro-renal syndrome of Lowe exhibited delays in developmental milestones, muscular weakness and hypotonia, and high serum creatine kinase activity. The biopsied muscle revealed selective type 1 fiber atrophy and mild type 1 fiber predominance, similar to that observed in congenital fiber type disproportion myopathy. The abnormal fiber type distribution may be responsible for the common finding of muscle hypotonia in this syndrome.     

Somatic and behavioral ontogeny in three rat strains: preliminary observations of dopamine-mediated behaviors and brain D-1 receptors.

1. The acquisition of developmental milestones and maturational motor reflexes were compared in three rat strains (culled to 8 pups/litter), F344, Buff and SD. 2. Open field behavior on postnatal day 21 was scored for locomotor activity, rears and center entries. 3. F344 rats, which model ADHD, were the slowest of the three strains in acquiring a number of developmental milestones and in gaining weight; but they were intermediate in their scores for locomotor activity and rearing during open field testing at postnatal day 21. 4. Preliminary autoradiographic data using the D-1 specific ligand [3H]SCH 23390 are included which suggest that D-1 receptors, which display age-dependent changes in concentration and distribution, are relevant to day 21 open field behavior. 5. F344 rats demonstrate developmental "dysmaturation" which is consistent with that observed in children with ADHD in that somatic growth is disproportionately delayed in comparison to neurological and motor maturation.     

A plausible model of schizophrenia must incorporate psychological and social, as well as neuro developmental, risk factors

Subtle alterations in brain development caused by genes or early environmental hazards, such as obstetric complications, play a role in projecting some individuals on a trajectory toward schizophrenia. High-risk and cohort studies demonstrate that children destined to develop schizophrenia tend to have delayed milestones and subtle neuromotor and cognitive impairments (particularly in coordination and language). These neurocognitive problems lead to difficulties in interpersonal relations, and their progressive alienation makes these at-risk children more likely to harbor odd or paranoid ideas. This cascade of increasingly deviant development may then be compounded by brain maturational changes during adolescence with a resultant lability of the dopaminergic response to stress. As a result, the individual is more susceptible to the effects of the abuse of dopamine-releasing drugs, and to other risk factors such as migration or stressful life events; social isolation may be a common pathway underlying several of the social risk factors.     

Clinical milestones in Parkinson's disease: A 7-year population-based incident cohort study

IntroductionClinical staging of Parkinson's disease (PD) is important for patient management and prognosis. The non-motor and functional features visual hallucinations, recurrent falls, dementia and nursing home placement are currently not included in clinical staging schemes, but have been suggested as clinical milestones with important prognostic implications in advanced PD. In this study, we sought to evaluate the potential of these four milestone events for clinical staging and prognosis during the early years of the disease.MethodsWe recruited 185 patients with incident PD and monitored prospectively every six months through seven years for emergence and consequences of four clinical milestones.ResultsOne or more milestones were reached in 53.0%. Of the patients who reached the milestones, visual hallucinations appeared after a median of 3.3 (interquartile range 1.3–4.9) years from diagnosis, recurrent falls after 3.8 (2.8–5.2) years, dementia after 4.0 (2.1–4.8) years and nursing home placement after 5.4 (3.9–6.7) years. Presence of any milestone was associated with occurrence of other milestones (relative risks 1.9–6.3; all p ≤ 0.001). Experiencing two or more milestones increased the risk of death during the study (relative risk 2.7, p = 0.03).ConclusionsIn early PD, visual hallucinations, recurrent falls, dementia and nursing home placement appear closely interrelated, possibly reflecting a shared neuropathological disease stage. All events convey important and sinister information on PD status and prognosis and are relatively easily accessible during routine clinical consultations. Therefore, they appear highly useful as clinical PD milestones and could possibly be incorporated into a novel disease rating scale.     

Gonadal Steroids have Paradoxical Effects on Brain Oxytocin Receptors

Specific brain receptors for oxytocin have been described in several mammalian species. The distribution of these receptors differs greatly across species and in the rat, receptor binding in specific brain regions appears to depend upon gonadal steroids. This study used in vitro receptor autoradiography to examine the effects of testosterone on oxytocin receptor binding in the mouse forebrain. Three groups of male mice were compared: castrates treated with blank capsules, castrates treated with testosterone filled capsules, and intact males. Irrespective of steroid treatment, the distribution of oxytocin receptors in mouse forebrain differed markedly from patterns previously described in the rat. In addition to these species differences in receptor distribution, testosterone had effects in the mouse which differed from the induction of receptors previously reported in the rat. In the mouse ventromedial nucleus of the hypothalamus, binding in the untreated castrate males was approximately double that observed in either the intact or the testosterone-treated castrates. In other regions of the mouse brain, such as the intermediate zone of the lateral septum, binding to oxytocin receptors was increased with testosterone treatment. These results suggest that the brain oxytocin receptor varies across species not only in its distribution but also in its regional regulation by gonadal steroids. These apparently paradoxical changes in oxytocin receptor binding may result from either direct or indirect effects of gonadal steroids in mouse brain.     

Basic fibroblast growth factor (bFGF) immunolocalization in the rodent outer retina demonstrated with an anti-rodent bFGF antibody

The distribution of bFGF in mouse and rat retinas was established using an antibody generated against a rat specific bFGF sequence. The patterns established with this antibody were distinctly different in comparison to the immunostaining patterns using antibodies prepared against similar regions of bovine and human bFGF sequences. Using the anti-rat antibody, at postpartum day 5, both species demonstrate bFGF-like labeling in the outer retina, primarily associated with developing photoreceptors. The anti-rat bFGF antibody in the adult mouse produces intense labeling at the level of the photoreceptor outer segment, whereas in the adult rat, Müller's cells and RPE were intensely labeled but the photoreceptors appeared to be unlabeled. In contrast, the bovine and human antibodies consistently label ganglion cells in both mouse and rat retinas, cells in the inner aspect of the inner nuclear layer and developing horizontal cells, whereas no photoreceptor labeling was observed. These results suggest that minor species differences in a short segment of the bFGF molecule used to generate these antibodies may result in major differences in apparent bFGF-like immunolocalization.     

Ultrastructural immunolocalization of rat oxytocin-neurophysin in transgenic mice expressing the rat oxytocin gene.

Cell-specific expression of the rat oxytocin (OT)-neurophysin transgene in mice was achieved using a construct containing both OT and vasopressin genes (Young III, W.S., Reynolds, K., Shepard, E.A., Gainer, H. and Castel, M., Cell-specific expression of the rat oxytocin gene in transgenic mice, J. Neuroendocrinol., 2 (1990) 1-9). The present study describes the distribution of the protein products of these genes in various regions of the cell, and determines whether the transgenic rat and endogenous mouse OT-neurophysins are colocalized within the same neurosecretory granules. Two monoclonal antibodies against OT-neurophysins were used: PS38 which can react with both rat and mouse OT-neurophysin (pan-specific), and PS67 which is specific for rat OT-neurophysin only. Various approaches to double immunolabeling at the ultrastructural level were employed; these included: (1) pre-embedding immunoperoxidase followed by post-embedding immunogold; (2) post-embedding immunolabeling using gold particles of different sizes; and (3) labeling of consecutive ultrathin sections with different antibodies. Results from each of these approaches showed that both in the transgenic mouse and in the rat (used as control), immunocytochemical labeling for both PS38 and PS67 occurred in the same OT-ergic neurosecretory granules. In the control mouse, only PS38 elicited labeling. Hence, it may be concluded that the protein and peptide products of the transgene and the endogenous gene for OT-neurophysin are being processed similarly in the cell and finally concentrated together in the same neurosecretory granules.     

Distinctive responses of brain tumor cells to TLR2 ligands:

Malignant brain tumor mass contains significant numbers of infiltrating glial cells that may intimately interact with tumor cells and influence cancer treatments. Understanding of characteristic discrepancies between normal GLIA and tumor cells would, therefore, be valuable for improving anticancer therapeutics. Here, we report distinct differences in toll‐like receptors (TLR)?2‐mediated responses between normal glia and primary brain tumor cell lines. We found that tyrosine phosphorylation of STAT1 by TLR2 ligands and its downstream events did not occur in mouse, rat, or human brain tumor cell lines, but were markedly induced in normal primary microglia and astrocytes. Using TLR2‐deficient, interferon (IFN)‐γ‐deficient, and IFNγ‐receptor‐1‐deficient mice, we revealed that the impaired phosphorylation of STAT1 might be linked with defective TLR2 system in tumor cells, and that a TLR2‐dependent pathway, not IFNγ‐receptor machinery, might be critical for tyrosine STAT1 phosphorylation by TLR2 ligands. We also found that TLR2 and its heterodimeric partners, TLR1 and 6, on brain tumor cells failed to properly respond to TLR2 ligands, and representative TLR2‐dependent cellular events, such as inflammatory responses and cell death, were not detected in brain tumor cells. Similar results were obtained in in vitro and in vivo experiments using orthotopic mouse and rat brain tumor models. Collectively, these results suggest that primary brain tumor cells may exhibit a distinctive dysfunction of TLR2‐associated responses, resulting in abnormal signaling and cellular events. Careful targeting of this distinctive property could serve as the basis for effective therapeutic approaches against primary brain tumors. GLIA 2015;63:894–905     

Vasoactive intestinal peptide in the brain of a mouse model for Down syndrome

The most common genetic cause of mental retardation is Down syndrome, trisomy of chromosome 21, which is accompanied by small stature, developmental delays, and mental retardation. In the Ts65Dn segmental trisomy mouse model of Down syndrome, the section of mouse chromosome 16 most homologous to human chromosome 21 is trisomic. This model exhibits aspects of Down syndrome including growth restriction, delay in achieving developmental milestones, and cognitive dysfunction. Recent data link vasoactive intestinal peptide malfunction with developmental delays and cognitive deficits. Blockage of vasoactive intestinal peptide during rodent development results in growth and developmental delays, neuronal dystrophy, and, in adults, cognitive dysfunction. Also, vasoactive intestinal peptide is elevated in the blood of newborn children with autism and Down syndrome. In the current experiments, vasoactive intestinal peptide binding sites were significantly increased in several brain areas of the segmental trisomy mouse, including the olfactory bulb, hippocampus, cortex, caudate/putamen, and cerebellum, compared with wild-type littermates. In situ hybridization for VIP mRNA revealed significantly more dense vasoactive intestinal peptide mRNA in the hippocampus, cortex, raphe nuclei, and vestibular nuclei in the segmental trisomy mouse compared with wild-type littermates. In the segmental trisomy mouse cortex and hippocampus, over three times as many vasoactive intestinal peptide-immunopositive cells were visible than in wild-type mouse cortex. These abnormalities in vasoactive intestinal peptide parameters in the segmental trisomy model of Down syndrome suggest that vasoactive intestinal peptide may have a role in the neuropathology of Down-like cognitive dysfunction.     

Localization of TREK-1, a two-pore-domain K+ channel in the peripheral vestibular system of mouse and rat

The distribution of two-pore-domain (2P-domain) K(+) channels of the TREK subfamily was studied using immunocytochemistry in the peripheral vestibular system of mouse and rat. Using RT-PCR, the mRNA for TREK-1, but not for TREK-2 or TRAAK, were detected in mouse vestibular endorgans and ganglia. The TREK-1 channel protein was immunodetected in both nerve fibers and nerve cell bodies in the vestibular ganglion, both afferent fibers and nerve calyces innervating type I hair cells in the utricle and cristae. The post-synaptic localization in afferent calyces may suggest a neuroprotective role in glutamatergic excitotoxicity during ischemic conditions. In non-neuronal cells, TREK-1 was immunodetected in the apical membrane of dark cells and transitional cells, both of which are involved in endolymph K(+) secretion and recycling. TREK-1 may subserve some neuroprotective function in afferent nerve fibers as well as play a role in endolymph potassium homeostasis.     

Differential expression of secretagogin immunostaining in the hippocampal formation and the entorhinal and perirhinal cortices of humans,rats, and mice

Secretagogin (SCGN) is a recently discovered calcium-binding protein belonging to the group of EF-hand calcium-binding proteins. SCGN immunostaining has been described in various regions of the human, rat and mouse brain. In these studies, it has been reported that, in general, the patterns of SCGN staining differ between rodents and human brains. These differences have been interpreted as uncovering phylogenetic differences in SCGN expression. Nevertheless, an important aspect that is not usually taken into account is that different methods are used for obtaining and processing brain tissue coming from humans and experimental animals. This is a critical issue since it has been shown that post-mortem time delay and the method of fixation (i.e., perfused vs. nonperfused brains) may influence the results of the immunostaining. Thus, it is not clear whether differences found in comparative studies with the human brain are simply due to technical factors or species-specific differences. In the present study, we analyzed the pattern of SCGN immunostaining in the adult human hippocampal formation (DG, CA1, CA2, CA3, subiculum, presubiculum, and parasubiculum) as well as in the entorhinal and perirhinal cortices. This pattern of immunostaining was compared with rat and mouse that were fixed either by perfusion or immersion and with different post-mortem time delays (up to 5 hr) to mimic the way the human brain tissue is usually processed. We found a number of clear similarities and differences in the pattern of labeling among the human, rat, and mouse in these brain regions as well as between the different brain regions examined within each species. These differences were not due to the fixation.     

The role of vertebrate models in understanding craniosynostosis

BACKGROUND: Craniosynostosis (CS), the premature fusion of cranial sutures, is a relatively common pediatric anomaly, occurring in isolation or as part of a syndrome. A growing number of genes with pathologic mutations have been identified for syndromic and nonsyndromic CS. The study of human sutural material obtained post-operatively is not sufficient to understand the etiology of CS, for which animal models are indispensable. DISCUSSION: The similarity of the human and murine calvarial structure, our knowledge of mouse genetics and biology, and ability to manipulate the mouse genome make the mouse the most valuable model organism for CS research. A variety of mouse mutants are available that model specific human CS mutations or have CS phenotypes. These allow characterization of the biochemical and morphological events, often embryonic, which precede suture fusion. Other vertebrate organisms have less functional genetic utility than mice, but the rat, rabbit, chick, zebrafish, and frog provide alternative systems in which to validate or contrast molecular functions relevant to CS.     

Cellular and subcellular localization of Huntingtin [corrected] aggregates in the brain of a rat transgenic for Huntington disease

Huntington disease (HD) is a progressive neurodegenerative disorder characterized by emotional, cognitive, and motor dysfunctions. Aggregation of huntingtin is a hallmark of HD and, therefore, a crucial parameter for the evaluation of HD animal models. We investigated here the regional, cellular, and subcellular distribution of N-terminal huntingtin aggregates and associated neuropathological changes in the forebrain of a rat transgenic for HD (tgHD). The tgHD rat brain showed enormously enlarged lateral ventricles and a similar atrophy of cortical and subcortical areas as known in HD patients. Huntingtin aggregates of varying size and forms were regionally identified in neuronal nuclei, cytoplasm, dendrites, dendritic spines, axons, and synaptic terminals, closely resembling the results described earlier for human HD brains and in established HD mouse models. Huntingtin aggregates in mitochondria support mitochondrial dysfunction as contributing to the disease pathogenesis. Dark cell degeneration was reminiscent of results in HD individuals and HD mouse models. Interestingly, huntingtin aggregates were especially well accumulated in two interacting limbic forebrain systems, the ventral striatopallidum and the extended amygdala, which may contribute to the early onset of emotional changes observed in the tgHD rat. In conclusion, the tgHD rat model reflects to a remarkable extent the cellular and subcellular neuropathological key features as observed in human HD and HD mouse brains and hints of changes in limbic forebrain systems, which may elucidate the emotional dysfunction in the tgHD rat and affective disturbances in HD patients.     

Through a mother's lens: a qualitative analysis reveals how temporal experience shifts when a boy born preterm has cystic fibrosis

We present a qualitative case study of one woman's experience of bringing up a child with cystic fibrosis (CF), born prematurely, using interpretative phenomenological analysis (IPA). This mother's existential account portrays time sequences for developmental milestones and synchronization of lifecycle events as atypical. Her perception of her child fluctuated radically; illness seemed to displace time, which collapsed with adversity. The temporal relations of CF and preterm birth are blurred at certain points. Although the challenge of compromised health may in some ways have promoted her son's development, his immature self-expression moved this mother towards an insider perspective of his experience. Cystic fibrosis is an ominous presence that demands respect even when the child is well. Anticipating the psychological impact of biomedical interventions can help to minimize trauma and maximize adaptation. Talking and play at transitional time points may assist the way parents and children assimilate temporal disruptions.     

Na,K-ATPase: comparison of the cellular localization of alpha-subunit mRNA and polypeptide in mouse cerebellum, retina, and kidney

A clone encoding mouse brain Na,K-ATPase alpha-subunit was isolated from a mouse brain lambda gt11 cDNA library by using antisera to mouse and bovine brain alpha-subunit. A comparison of the nucleotide sequence of this clone with published sequences of rat brain alpha-subunit isoform clones showed it to be most similar to rat brain alpha 1. An RNA antisense probe prepared from the cDNA insert of the mouse clone detected a single mRNA of approximately 4.5 kb in Northern blots of mouse brain and kidney RNAs. This probe hybridized only to an alpha 1-cDNA insert from rat brain under high stringency conditions on Northern blots. The RNA antisense probe was used for in situ hybridization to sections of mouse kidney, cerebellum, and retina, and the cellular distribution of alpha-subunit mRNA (alpha-mRNA) was compared with that of alpha-subunit polypeptide (alpha-subunit) detected by immunofluorescence in similar sections. In kidney, alpha-mRNA distribution closely paralleled that of the polypeptide with abundant expression in ascending thick limbs and cortical distal tubules and weaker labeling in cortical proximal tubules. The co-distribution of alpha-mRNA and polypeptide in kidney where Na,K-ATPase localization is well established is consistent with the specificity of these probes. In the retina, prominent labeling with both probes was seen in photoreceptor inner segments, inner nuclear layer, and ganglion cell bodies. Plexiform layers and optic fibers expressed abundant alpha-subunit but little mRNA. Light labeling for both was seen in the outer nuclear layer. In cerebellum, alpha-mRNA and alpha-subunit were associated with soma of granule cells, basket cells, and stellate cells. Glomeruli and basket terminals contained abundant alpha-subunit but exhibited little reactivity with the riboprobe. In Purkinje cell bodies, in contrast, the antibody used to identify the cDNA clone did not resolve significant polypeptide in the somal plasmalemma despite abundant somal mRNA expression. Comparison of distribution of the two probes in cerebellum and retina indicates that message accumulation is primarily in cell bodies, while alpha-subunit epitopes may be co-expressed in cell bodies and/or transported to distant sites in cell-specific patterns.     

DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein: regional, tissue, and phylogenetic distribution

Rabbit antisera and mouse monoclonal antibodies have been prepared to bovine DARPP-32 (dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein, Mr = 32,000), and used to study its regional, tissue, and phylogenetic distributions. The antibodies, none of which distinguished between dephospho-DARPP-32 and phospho-DARPP-32, were characterized and used to develop a sensitive and specific radioimmunoassay for DARPP-32. The radioimmunoassay, in conjunction with immunolabeling of SDS/PAGE transfers and immunoprecipitation of phosphorylated tissue extracts, was used to measure immunoreactive DARPP-32 in microdissected regions of rat CNS, in peripheral nervous and non-nervous tissues, and in CNS tissue from various animal species. The distribution of DARPP-32 was generally consistent with the interpretation that it is localized primarily to dopaminoceptive cells that possess dopamine-sensitive adenylate cyclase (D-1 dopamine receptors coupled to adenylate cyclase). Within the rat CNS, DARPP-32 was most highly concentrated in the basal ganglia. DARPP-32 was present in neostriatum from all six mammalian species tested (mouse, rat, guinea pig, rabbit, cow, and rhesus monkey) at concentrations of from 96 to 144 pmol/mg total protein, which constituted from 0.22 to 0.32% of the total protein. DARPP-32 was also identified at low levels in several peripheral tissues, including choroid plexus, parathyroid cells, adrenal chromaffin cells, posterior pituitary gland, pineal gland, and superior cervical sympathetic ganglion. A phylogenetic survey was carried out of proteins immunologically related to DARPP-32 in nervous tissue from nonmammalian species. DARPP-32-like proteins were identified in dopaminoceptive brain regions from representative members of the amniote vertebrate classes (birds and reptiles), while none was identified in dopaminoceptive brain regions from representative members of the anamniote vertebrate classes (bony fishes and amphibians) or in nervous tissue from representative members of several invertebrate classes.     

Attractin/mahogany protein expression in the rodent central nervous system

Attractin/Mahogany protein (Atrn) is known to be involved in a number of physiological and neuropathological events. Although the ubiquitous distribution of atrn mRNA has been described in neurons, lack of detailed information concerning the cellular and subcellular localization of protein product is impeding understanding of the role of Atrn. The present study immunohistochemically examined distributions of Atrn in rat and mouse central nervous systems (CNSs) by using a novel antibody for Atrn. Atrn was intensely expressed in most neurons and dendrites of large neurons, such as cortical pyramidal neurons and cerebellar Purkinje neurons. Intense Atrn expression was also observed in the neuropil of gray matter in many regions of the CNS, such as the main and accessory olfactory bulb, cerebral cortex, caudate putamen, dorsal lateral geniculate nucleus, medial eminence, superior colliculus, hippocampus, dentate gyrus, and layers 1 and 2 of the spinal cord. Furthermore, we found that astrocytes, microglia, and ependymal cells also express Atrn protein. Immunoelectron microscopy showed the subcellular distribution of Atrn in the plasma membrane of cell soma, dendrites, and spines in neurons and in the cytoplasmic membrane of Golgi apparatus, endoplasmic reticulum, and mitochondria in neurons and glial cells. These findings indicate that Atrn is more widely expressed throughout the CNS than previously reported, and expression of Atrn by various cell types suggests that Atrn may serve multiple functions in the CNS.