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PubMed1997

Striatal synaptophysin levels are not indicative of dopaminergic supersensitivity.

Recent evidence suggests that behavioral supersensitivity to dopamine (DA) agonists observed in chronic neuroleptic-treated animals might be related to changes in synaptic morphology and density. The aim of this study was to test this hypothesis using Western blotting to determine the striatal synaptophysin levels in rats chronically treated with haloperidol followed by sub-acute administration of a DA agonist. Chronic haloperidol treatment (1 mg/kg/day for 21 days) produced an 88% increase in striatal synaptophysin levels and a 73% increase in apomorphine-induced stereotypes. Sub-acute administration of the DA D-1 receptor agonist SKF38393 (10 mg/kg/day for 5 days) or the DA D-2 receptor agonist quinpirole (1 mg/kg/day for 5 days) did not modify the haloperidol-induced increase in striatal synaptophysin levels. However, sub-acute administration of SKF38393 attenuated (62%) haloperidol-induced stereotypies. We conclude that there is no direct relationship between stereotyped behavior and synaptophysin levels indicating that striatal synaptophysin levels are not a good marker of dopaminergic supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2004

[Synaptophysin expression abnormalities in Hirschsprung's disease].

Hirschsprung's disease is defined by the congenital absence of ganglion cells in enteric plexuses. Immunostaining of synaptophysin after formalin fixation may be used to identify hyperplasia of nerve fibers and rarefaction of neuromuscular junctions in Hirschsprung's disease. The aim of the study was to evaluate semi-quantitatively the expression of synaptophysin in Hirschsprung's disease, in correlation with morphologic features. This retrospective study included 3 controls, 42 surgical rectal biopsies performed for suspicion of Hirschsprung's disease in children presenting with lower digestive occlusion or severe chronic constipation, including 18 Hirschsprung's disease, and 23 surgical specimens of Hirschsprung's disease. In the absence of Hirschsprung's disease, synaptophysin-positive fibers were numerous but thin in the muscularis mucosae, thin and scarce in the mucosa and submucosa. Neuromuscular junctions were thin and numerous in the muscularis propria. In Hirschsprung's disease, synaptophysin-positive fibers were coarse, and increased in number on each side of the muscularis mucosae. Plexuses were enlarged, weakly stained, and associated in the connective tissue of the muscularis propria with coarse and intensely stained fibers. In conclusion, staining for synaptophysin could be useful to demonstrate abnormalities of enteric innervation in rectal biopsies performed for suspected Hirschsprung's disease in the absence of acetylcholinesterase staining on frozen sections, in transmural biopsies performed for guiding surgery in Hirschsprung's disease, and in cases of extensive Hirschsprung's disease.

Acetylcholinesterase↗
PubMed2002

Altered synaptophysin expression in the rat spinal cord after chronic constriction injury of sciatic nerve.

Injury to the peripheral nervous system can lead to spontaneous pain, hyperalgesia and allodynia. Previous studies have shown sprouting of Abeta-fibres into lamina II of the spinal cord dorsal horn after nerve injury and the formation of new synapses by these sprouts. Synaptophysin is a presynaptic vesicle protein, useful in the identification of synaptogenesis. Here we investigated whether synaptogenesis as measured by the expression of synaptophysin protein correlates with symptoms of neuropathic pain in rats with a chronic constriction injury (CCI) of the sciatic nerve. We used immunohistochemistry, Western immunoblotting and densitometry to study the distribution of synaptophysin and to quantify relative protein. Synaptophysin was increased in the ipsilateral dorsal horn with a peak level on day 14 and returned to baseline on day 21 post-CCI. Synaptophysin levels temporally correlated with thermal hyperalgesia but not with tactile allodynia. Our results indicate that thermal hyperalgesia in CCI significantly correlates with synaptogenesis within the superficial layers of the dorsal horn.

Animals↗
PubMed2002

Activity-dependent changes in synaptophysin immunoreactivity in hippocampus, piriform cortex, and entorhinal cortex of the rat.

Synaptophysin, an integral membrane glycoprotein of synaptic vesicles, has been widely used to investigate synaptogenesis in both animal models and human patients. Kindling is an experimental model of complex partial seizures with secondary generalization, and a useful model for studying activation-induced neural growth in adult systems. Many studies using Timm staining have shown that kindling promotes sprouting in the mossy fiber pathway of the dentate gyrus. In the present study, we used synaptophysin immunohistochemistry to demonstrate activation-induced neural sprouting in non-mossy fiber cortical pathways in the adult rat. We found a significant kindling-induced increase in synaptophysin immunoreactivity in the stratum radiatum of CA1 and stratum lucidum/radiatum of CA3, the hilus, the inner molecular layer of the dentate gyrus, and layer II/III of the piriform cortex, but no significant change in layer II/III of the entorhinal cortex, 4 weeks after the last kindling stimulation. We also found that synaptophysin immunoreactivity was lowest in CA3 near the hilus and increased with increasing distance from the hilus, a reverse pattern to that seen with Timm stains in stratum oriens following kindling. Furthermore, synaptophysin immunoreactivity was lowest in dorsal and greatest in ventral sections of both CA3 and dentate gyrus in both kindled and non-kindled animals. This demonstrates that different populations of sprouting axons are labeled by these two techniques, and suggests that activation-induced sprouting extends well beyond the hippocampal mossy fiber system.

Animals↗
PubMed2000

Synaptophysin immunoreactivity in spinal white matter of young adult rats.

Patterns of synaptophysin immunoreactivity were examined in the ventral and lateral funiculi of rat lumbosacral spinal cords. In normal young adults, dendrites from neurons in the spinal gray matter extended into the ventral and lateral white matter as finger-like projections, immunopositive for synaptophysin. These projections appeared to diminish in size as they extended peripherally and, in general, did not reach the surface of the spinal cord, so that the outer one-third to one-fourth of the funiculi contained little or no immunoreactivity. The spinal cords of some of the animals studied were X-irradiated on the third postnatal day. When examined 6 weeks to 5 months later, the pattern of synaptophysin immunoreactivity was found to be markedly altered in these animals. In general, the synaptophysin immunoreactivity in the white matter was less organized than in the non-irradiated rat. As a result, the finger-like projections, particularly into the lateral funiculi, were not as distinct, and the immunoreactivity appeared to be more diffusely distributed in the white matter. Further, the immunoreactivity was present throughout the thickness of the white matter in the irradiated animals and subpial concentrations were evident, especially along the lateral aspect of the spinal cord. Ultrastructural evaluation of the synaptic profiles revealed no differences between irradiated and non-irradiated animals. The synapses occurred on both the shafts of the dendrites and on the spines. In general, both dendrites and axon terminals were covered by astrocyte processes except at synaptic sites, and the synaptic complexes were surrounded by astrocyte processes. Although the mechanisms underlying the altered pattern of synaptophysin immunoreactivity are not yet understood, they may be related to radiation-induced effects on the glial populations previously reported by the investigators and/or to radiation-induced alterations in reorganization or maturation of dendritic trees.

Animals↗
PubMed1996

The V0 sector of the V-ATPase, synaptobrevin, and synaptophysin are associated on synaptic vesicles in a Triton X-100-resistant, freeze-thawing sensitive, complex.

Anti-synaptobrevin 2 immunoprecipitates obtained from freshly prepared Triton X-100 extracts of rat synaptosomes contained, in addition to synaptophysin, a 10-kDa band, which we identified by peptide sequencing and Western blotting as the c subunit of the vacuolar proton pump (V-ATPase) also called ductin or mediatophore. Ac39 and Ac116, two other transmembrane subunits of the V0 sector of the V-ATPase, were also found by Western blotting to be enriched in the immunoprecipitates. None of these V-ATPase subunits, or synaptophysin, was present in anti-synaptobrevin 2 immunoprecipitates obtained from frozen-thawed Triton X-100 extracts, which were greatly enriched, instead, in SNAP-25 and syntaxin 1. Accordingly, V-ATPase subunit c was found in anti-synaptophysin immunoprecipitates. Thus, the two complexes appear to be mutually exclusive. Subcellular fractionation of rat brain demonstrated that V-ATPase subunit c is localized with synaptobrevin 2 and synaptophysin in synaptic vesicles. The coprecipitation of V-ATPase subunit c with the synaptobrevin-synaptophysin complex suggests that this interaction may play a role in recruiting the proton pump into synaptic vesicles. Freeze-thawing, which involves a mild denaturing step, may produce a conformational change which dissociates the complex and mimics a change which occurs in vivo as a prerequisite to SNARE complex formation.

Amino Acid Sequence↗
PubMed1996

Pantophysin is a ubiquitously expressed synaptophysin homologue and defines constitutive transport vesicles.

Certain properties of the highly specialized synaptic transmitter vesicles are shared by constitutively occurring vesicles. We and others have thus identified a cDNA in various nonneuroendocrine cell types of rat and human that is related to synaptophysin, one of the major synaptic vesicle membrane proteins, which we termed pantophysin. Here we characterize the gene structure, mRNA and protein expression, and intracellular distribution of pantophysin. Its mRNA is detected in murine cell types of nonneuroendocrine as well as of neuroendocrine origin. The intron/exon structure of the murine pantophysin gene is identical to that of synaptophysin except for the last intron that is absent in pantophysin. The encoded polypeptide of calculated mol wt 28,926 shares many sequence features with synaptophysin, most notably the four hydrophobic putative transmembrane domains, although the cytoplasmic end domains are completely different. Using antibodies against the unique carboxy terminus pantophysin can be detected by immunofluorescence microscopy in both exocrine and endocrine cells of human pancreas, and in cultured cells, colocalizing with constitutive secretory and endocytotic vesicle markers in nonneuroendocrine cells and with synaptophysin in cDNA-transfected epithelial cells. By immunoelectron microscopy, the majority of pantophysin reactivity is detected at vesicles with a diameter of < 100 nm that have a smooth surface and an electron-translucent interior. Using cell fractionation in combination with immunoisolation, these vesicles are enriched in a light fraction and shown to contain the cellular vSNARE cellubrevin and the ubiquitous SCAMPs in epithelial cells and synaptophysin in neuroendocrine or cDNA-transfected nonneuroendocrine cells and neuroendocrine tissues. Pantophysin is therefore a broadly distributed marker of small cytoplasmic transport vesicles independent of their content.

3T3 Cells↗
PubMedDate not supplied

Synaptophysin immunohistochemistry during vestibular hair cell recovery after gentamicin treatment.

In the present study, morphometric and immunohistochemical techniques were used to evaluate the degree of synaptic recovery in the chinchilla crista sensory epithelia during various post-gentamicin-treatment periods of hair cell loss and recovery. For this purpose, two groups of animals were treated with Gelfoam pellets impregnated with 50 micro g of gentamicin implanted in the perilymphatic space within the otic capsule of the superior semicircular canal. Animals were sacrificed 1, 2 and 4 weeks after treatment. The degree of synaptic reinnervation was evaluated in the horizontal crista of the first group of animals using immunohistochemical techniques and antibodies against synaptophysin, a marker for synaptic reinnervation and synaptogenesis. Quantification of immunoreactivity in this group was made in the mid-region of the crista using the NIH 'Image' program. The second group of animals was used for quantification of the number of hair cells and supporting cells in the horizontal crista. In the normal sensory epithelium, synaptophysin immunoreactivity was found in the areas corresponding to the known distribution of afferent and efferent nerve terminals. Immunoreactivity was predominantly located within the afferent calyces of type I hair cells. No immunoreactivity was found in the supporting cells. Seven days after treatment there was a significant loss of hair cells and synaptophysin-stained area (SSA). In the mid-region of the crista the loss of synaptophysin immunoreactivity was quantitatively the greatest within the central zone of this region (93%) while the loss of hair cells was the smallest. These results suggest that afferent and efferent nerve terminals were also severely affected by the ototoxic treatment. Four weeks after treatment corresponding to the end of the recovery phase of gentamicin ototoxicity, there was a proportional increase in the number of hair cells and of the degree of SSA in the mid-region of the crista. The number of hair cells recovered to 58% with a recovery of SSA to 54% of normal. These results suggest that a greater fraction of synaptophysin expression within the sensory epithelium depends on the presence of afferent calyceal endings, which are greatly affected by gentamicin. Also, these results demonstrate a significant level of reinnervation of the newly regenerated hair cells, forecasting the potential for functionality of the regenerated hair cells.

Animals↗
PubMedDate not supplied

Synaptophysin immunoreactivity is stable 36 h postmortem.

The effects of postmortem time, age and tissue storage time on synaptic density were investigated in the prefrontal cortex of human brains. Thirty normal cases and 10 patients with a variety of neurologic diseases were studied, using quantitative immunohistochemistry with a monoclonal antibody to synaptophysin. Synaptophysin immunoreactivity was stable during the first 36 h after death, showing no significant change at 1, 8, 12, 24 and 36 h postmortem in normals. However, at 48 and 72 h postmortem, synaptophysin immunoreactivity decreased significantly. A similar pattern of postmortem changes was found in the disease group. In 14 normal cases with a wide range of ages, a significant reduction in synaptic density with age was observed while the time of tissue storage as paraffin-embedded blocks had no significant effect on the synaptophysin immunoreactivity. These results support the validity of using synaptophysin immunohistochemistry as a measure of synaptic density in human brain autopsied within 36 h of death and stored as paraffin-embedded blocks for a long time.

Age Factors↗
PubMedDate not supplied

Quantitative assessment of the synaptophysin immuno-reactivity of the cortical neuropil in various neurodegenerative disorders with dementia.

It has remained a matter of debate until now whether amyloid and tangle pathology may be regarded as the main causes of the dementia in Alzheimer's disease (AD) or only as markers of the disease. In the present study we examined the synaptophysin immunoreactivity of the cortical neuropil as a measure of its synapse density, in 17 cases of AD, 1 case with a 10-month episode of dementia and cortical amyloid deposition, 5 cases of Huntington's disease (HD) with dementia, 11 cases of parkinsonism (PD), 5 with dementia (PD-D) and 16 controls. The immunoreactivity was assessed in two layers (molecular, pyramidal) of three regions (frontal, occipital, hippocampus) by means of automated black-and-white image analysis. In AD we found a rather diffuse reduction of the cortical synaptophysin expression of up to 26.5% (mean 11%) of the controls. No correlation was found between synaptophysin expressivity and age either in AD or in the controls. Univariate analyses revealed only a very weak negative correlation between the density of beta A4-immunoreactive cortical plaques and the intensity of the synaptophysin staining, while in a multivariate analysis the plaque density did not show any impact on the latter. In HD a reduction of the synaptophysin immunoreactivity of the cortical neuropil was also found (mean 10.4%), with a predominance in the pyramidal layer of the neocortex. The same was true for PD (5.3%) and PD-D (8.2%). Our results support the view that loss of synapses in the cortical neuropil may be a significant factor for the development of organic dementia, while the amyloid pathology in AD is more likely a marker of the disease.

Adult↗
PubMed1999

Detection of synaptophysin-producing cells in human thymus by immunohistochemistry and nonradioactive in situ hybridization.

We investigated human thymic tissue by immunohistochemistry and in situ hybridization for the presence of synaptophysin-producing cells. Our results indicate that anti-synaptophysin antibody detected immunoreactive material in nerve fibers around vessels located in major thymic septa, in a relevant number of cortical epithelial cells, and in scattered epithelial cells in the medulla. The epithelial nature of synaptophysin-positive cells was documented by the co-expression of cytokeratins as revealed by double immunofluorescence. In situ hybridization studies revealed the presence of synaptophysin mRNA in cells mainly located in the cortex, the specific fluorescent signals being localized in the cell cytoplasm. Western blot analysis using an affinity-purified polyclonal antibody revealed an immunoreactive band of about 38 kD in the extracts from unfractionated thymic tissue and from epithelial cell-enriched fractions. No staining was observed in isolated thymocytes. The expression of synaptophysin in epithelial cells of the thymic cortex suggests that this protein may be involved in secretory activities related to T-cell maturation.

Blotting, Western↗
PubMed1992

[Immunohistochemical studies using synaptophysin in intestinal biopsies in Hirschsprung disease].

Rectal biopsies of 5 children with Hirschsprung's disease and biopsies of 41 patients with chronic constipation of other causes, such as neuronal intestinal dysplasia, hypoganglionosis and chronic intestinal pseudo-obstruction (CIPSO), were investigated, using a monoclonal antibody against synaptophysin. Electron microscopy was performed in some cases. Synaptophysin, which stained adrenergic, cholinergic and neuroendocrine structures, as well, consequently, was not a suitable marker for one particular transmitter system. Normo-, hypo- and hyperganglionotic submucous plexuses were reliably stained. Hypertrophic submucosal nerve fibers, characteristic of Hirschsprung's disease, were of poor synaptophysin positivity, whereas acetylcholinesterase-positive mucosal nerve fibers exhibited stronger immunoreactivity. A comparable but regionally varying staining reaction in mucosal nerve fibers was found in CIPSO cases. Mucosal portions of histologically normal biopsies were synaptophysin-negative. Synaptophysin antibodies may support acetylcholinesterase investigation and thus are useful under diagnostic aspects. However, they are practicable neither for better distinction in differential diagnosis of Hirschsprung's disease nor for pathogenetic research.

Acetylcholinesterase↗
PubMed2004

Changes in synapses and axons demonstrated by synaptophysin immunohistochemistry following spinal cord compression trauma in the rat and mouse.

OBJECTIVE AND METHODS: To evaluate synaptic changes using synaptophysin immunohistochemstry in rat and mouse, which spinal cords were subjected to graded compression trauma at the level of Th8-9. RESULTS: Normal animals showed numerous fine dots of synaptophysin immunoreactivity in the gray matter. An increase in synaptophysin immunoreactivity was observed in the neuropil and synapses at the surface of motor neurons of the anterior horns in the Th8-9 segments lost immunoreactivity at 4-hour point after trauma. The immunoreactive synapses reappeared around motor neurons at 9-day point. Unexpected accumulation of synaptophysin immunoreactivity occurred in injured axons of the white matter of the compressed spinal cord. CONCLUSION: Synaptic changes were important components of secondary injuries in spinal cord trauma. Loss of synapses on motor neurons may be one of the factors causing motor dysfunction of hind limbs and formation of new synapses may play an important role in recovery of motor function. Synaptophysin immunohistochemistry is also a good tool for studies of axonal swellings in spinal cord injuries.

Animals↗
PubMed1990

Synaptophysin: structure of the human gene and assignment to the X chromosome in man and mouse.

Synaptophysin is an integral membrane protein of small synaptic vesicles in brain and endocrine cells. We have determined the structure and organization of the human synaptophysin gene and have established the chromosome localizations in man and mouse. Analysis of a cosmid clone containing the human synaptophysin gene (SYP) revealed seven exons distributed over approximately 20 kb, when compared with the previously published cDNA sequence. The exon-intron boundaries have been identified and do not correlate with functional domains. One intron interrupts the 3' untranslated region. Chromosomal localization of the human and murine genes for synaptophysin established the human SYP locus on the X chromosome in subbands Xp11.22-p11.23 and the mouse synaptophysin gene locus (Syp) on the X chromosome in region A-D. In addition, an Eco0109 RFLP has been identified and used in genetic mapping of the human SYP locus and supports the order TIMP-SYP-DXS14 within a span of approximately 4-7 centimorgans.

Amino Acid Sequence↗
PubMedDate not supplied

Immunohistochemistry of synapsin I and synaptophysin in human nervous system and neuroendocrine tumors. Applications in diagnostic neuro-oncology.

Synapsin I is a phosphoprotein localized to the cytoplasmic surface of synaptic vesicles and is one of the best characterized neuron-specific proteins. Synaptophysin is an integral membrane glycoprotein, also located on presynaptic vesicles, which has been shown to be a useful immunohistochemical marker for neuroendocrine/neuronal differentiation in tumor diagnosis. The sensitivity and specificity of immunohistochemical staining for these two proteins in formalin-fixed, paraffin-embedded tissues was studied in a series of 67 neuroectodermal, neuroendocrine, and non-neural tumors. Intense immunoreactivity for both synapsin I and synaptophysin was observed in tumors containing well-differentiated neurons (gangliocytoma, ganglioglioma, neurocytoma). In these tumors, immunostaining was primarily concentrated along the outer surface of the cell membrane of the neuronal cells. Primitive neuroectodermal tumors (PNETs) (cerebral PNET, medulloblastoma, neuroblastoma) and most neuroendocrine tumors generally showed less intense and more variable immunoreactivity for these proteins. In most cases, immunostaining for synapsin I was sharper and often more intense than for synaptophysin. Some PNETs and neuroendocrine tumors that were immunoreactive for synapsin I did not stain for synaptophysin. We conclude that synapsin I is a reliable, sensitive immunohistochemical marker for neuronal/neuroendocrine differentiation in human neoplasms and may offer some advantages over synaptophysin when applied to formalin-fixed, paraffin-embedded tissues, particularly in the evaluation of primitive neuroectodermal tumors and neuroendocrine tumors.

Brain Neoplasms↗
PubMed1996

Ultrastructural distribution of synaptophysin and synaptic vesicle recycling at the frog neuromuscular junction.

Synaptic vesicle recycling after intense acetylcholine (ACh) release was studied at the frog neuromuscular junction (NMJ) using the synaptic vesicle transmembrane protein synaptophysin as immunocytochemical marker of the synaptic vesicle membrane during the process of exo-endocytosis. ACh release in cutaneous pectoris nerve-muscle preparations was stimulated by three different means: K+, Cd2+ in Ca(2+)-free medium, and electrical stimulation in the presence of 4-aminopyridine (4-AP). Cd2+ stimulation produced synaptic vesicle depletion and nerve terminal swelling. Electrical stimulation in the presence of 4-AP produced a reduction in the number of synaptic vesicles, deep axolemmal infoldings, coated pits, and coated vesicles. K+ stimulation did not produce any observable ultrastructural changes. Synaptophysin was labeled using silver-intensified immunogold in dissociated muscle fibers. Unstimulated and K(+)-stimulated preparations showed synaptophysin immunolabeling associated only with synaptic vesicles. In contrast, in Cd(2+)-stimulated preparations, synaptophysin appeared along the axolemma, mainly at the active zones, and after electrical stimulation it appeared in both axolemmal infoldings and the remaining synaptic vesicles. The results show that when synaptic vesicle recycling is inhibited by Cd2+ in Ca(2+)-free medium, or when 4-AP is present during electrical stimulation, synaptic vesicle fusion is accompanied by translocation and incorporation of synaptic vesicle membrane proteins into the axolemma. However, during the latter condition, synaptic vesicles are recycled through coated vesicles arising from the axolemmal infoldings. Conversely, during physiological-like stimulation of ACh release by K+ the synaptic vesicles are rapidly recycled at the active zones, by a double and rapid process of exo-endocytosis, without collapse into the axolemma.

Acetylcholine↗
PubMed2002

Synaptophysin in the cochlear nucleus following acoustic trauma.

Chinchillas are notable for a low-frequency hearing range similar to that of humans and a marked sensitivity to loud noise. A single noise exposure that produces cochlear damage may lead to progressive loss of synaptic endings in the cochlear nucleus, followed by new axonal growth. As an index of synaptic regulation during such changes, we have examined the expression of a synaptic vesicle protein, synaptophysin, in the cochlear nucleus following a damaging acoustic stimulus in adult chinchillas. With one ear protected by a plug, following a 3-h exposure to an octave-band noise of 108 dB sound pressure level, centered at 4 kHz, the unprotected cochlea and the cochlear nuclei exhibited degeneration of hair cells and axons over periods of 7, 14, 30, 90, and 150 days. Axonal degeneration, as revealed by a silver degeneration method, was heavy ipsilateral to the cochlear damage, but sparse degeneration also appeared on the contralateral, unexposed side. Synaptophysin immunostaining underwent a major, bilateral decline in the anteroventral and posteroventral cochlear nuclei, interrupted at intervening periods by transient increases in the numbers of stained structures. A distinction in staining between large perisomatic structures and smaller puncta in the neuropil and between the dorsal and the ventral zones of the ventral cochlear nuclei revealed some variations in the response and degree of recovery of synaptophysin staining. These findings could best be explained by degeneration of synaptic endings followed by new growth of terminals and by regulatory changes in the levels of synaptophysin expression and synaptic vesicle accumulation over time.

Acoustic Stimulation↗
PubMed1996

Persistent alterations in regional brain glial fibrillary acidic protein and synaptophysin levels following pre- and postnatal polychlorinated biphenyl exposure.

Pregnant Wistar WU rats were exposed to 0, 5, and 25 mg of the commercial polychlorinated biphenyl (PCB) mixture Aroclor 1254 per kilogram of body weight on Days 10 to 16 of gestation. Pregnant rats were sacrificed on Gestation Day 20 to observe effects on fetal body and brain weights. Male and female offspring were sacrificed on Postnatal Days 21 and 90 (PND21 and PND90, respectively) and examined for treatment-related effects on neurochemical parameters. The concentrations of the neuronal and glial cell markers, synaptophysin and glial fibrillary acidic protein (GFAP), were measured in diverse brain regions from the offspring using immunochemical techniques. The level of calcineurin (a calmodulin-regulated protein phosphatase) activity was measured in cerebellar homogenates. In addition, ethoxyresorufin O-deethylase (EROD) activity was determined in hepatic microsomes as a measure of a well-characterized response to PCB exposure in experimental animals. The major alterations of GFAP levels following maternal PCB treatment were significant increases in the lateral olfactory tract (LOT) and the cerebellum (CB) and significant decreases in the brain stem (BS) of the offspring on PND21 and 90. Synaptophysin levels were significantly decreased relative to controls in the LOT, prefrontal cortex, and striatum of the offspring on PND90. In the BS, synaptophysin levels were significantly decreased relative to controls in male and female weanlings on PND21 and males on PND90; however, significant increases were observed in the BS of females on PND90. No effect of maternal PCB treatment was observed on levels of GFAP and synaptophysin in the dorsal hippocampus on PND21 and 90. Due to analytical restrictions statistical comparisons of GFAP levels were limited to examining the effect of maternal PCB treatment per brain region per sex per time point. Calcineurin activity was decreased in the female CB on PND21, but a significant increase in activity was observed in the female CB on PND90. No effect of maternal PCB treatment was observed on the cerebellar calcineurin activity in male offspring on PND21 and 90. EROD activity was highly induced in maternal microsomes from both PCB treatment groups, but only slightly induced in fetal hepatic microsomes. On PND21 weanling hepatic microsomal EROD activity was highly induced following gestational and lactational PCB exposure; however, on PND90 EROD activity was unaffected by maternal PCB treatment in male offspring and significantly decreased in female offspring. The results of the present study indicate that gestational and lactational exposure to the commercial PCB mixture results in long-term alterations in a neuronal and glial cell markers in specific brain regions of rats. These marker proteins may be useful for determining the structure-activity relationships in PCB-induced developmental neurotoxicity.

Animals↗