Demands during maze. learning in limbic epileptic rats: selective damage in the thalamus?

A qualitatively evident enhancement of chromolytic neurons within the lateral posterior thalamus of rats in which limbic seizures had been induced by lithium and pilocarpine and who were later trained for spatial memory was assessed quantitatively. The significant increase in the numbers of chromolytic neurons and the decrease in the numbers of normal neurons for these rats compared to the reference brains suggested these morphological changes were recent. The hypothesis that excessive stimulation of the lateral posterior nucleus by daily training in a radial maze may have facilitated the necrosis was supported by the inverse relationship between a linear combination of the numbers of normal neurons and oligodendroglia and the rate of learning during the earlier but not the later sessions. An implication for iatrogenic effects from rehabilitation of humans following brain injury was suggested.     

Postictal nose wiping: a lateralizing sign in temporal lobe complex partial seizures

We report postictal nose wiping as a postictal symptom of localizing and lateralizing significance in focal epilepsy. We reviewed videotapes of 444 focal seizures in 101 patients who underwent prolonged video and EEG monitoring during presurgical epilepsy evaluation, and observed postictal nose wiping in 51.3% of 76 patients with temporal lobe epilepsy. The hand used to perform postictal nose wiping was ipsilateral to the side of seizure origin in 86.5% of all seizures and in 97.3% of all patients. We conclude that postictal nose wiping is a common, easily assessed symptom after focal seizures of temporal lobe origin that provides reliable lateralizing information on the side of seizure onset.     

Heat shock induces rapid dephosphorylation of tau in both female and male rats followed by hyperphosphorylation only in female rats: implications for Alzheimer's disease

Female and male 2-3-month-old Sprague-Dawley rats were heat shocked at 42 degrees C for 15 min. At 0, 3, 6, 12 and 24 h after heat shock, qualitative and quantitative immunoblot analysis of cerebral extracts and immunohistochemistry were performed using monoclonal anti-tau antibodies that recognize nonphosphorylated (Tau-1), phosphorylated (PHF-1), and phosphate-independent (Tau-5 and Tau-46) epitopes. At 0 h after heat shock, there was dephosphorylation of tau in both female and male rats as evidenced by (1) accentuation and attenuation of tau isoforms recognized by Tau-1 and PHF-1, respectively, and recognition of additional tau polypeptides by Tau-1, Tau-5, and Tau-46 but not PHF-1; (2) significant increase in the nonphosphorylated Tau-1 epitope with resultant decrease in the ratio of total (phosphorylated plus nonphosphorylated) tau to nonphosphorylated tau; and (3) dephosphorylation of the Tau-1 epitope in the somatodendritic compartment. By 6 h after heat shock, there was progressive hyperphosphorylation of tau in female but not male rats exemplified by (1) upward gel mobility shift recognized by PHF-1, Tau-5, and Tau-46, and by Tau-1 after dephosphorylation; (2) significant increase in the ratio of total tau to nonphosphorylated tau; and (3) rephosphorylation of the Tau-1 epitope in the somatodendritic compartment. Two-dimensional electrophoresis showed shifts to basic and acidic tau polypeptides at 0 and 6 h after heat shock, respectively. Hyperphosphorylation of tau also occurred after multiple heat-shock episodes. Microtubules were present at 6 h after heat shock. There were no differences between control and heat-shocked rats in extracts from peripheral nerves. Thus, we now have a simple rat model to study within 6 h the processes of dephosphorylation and hyperphosphorylation of tau, which are altered in Alzheimer's disease.     

The effect of hypothalamic peptide YY on hippocampal acetylcholine release in vivo: implications for limbic function in binge-eating behavior

Central injection of peptide YY (PYY) in sated rats produces the most powerful stimulating effect of food intake known to date. The neural mechanisms by which PYY regulates appetite are not clear but may be important because abnormal levels of PYY have been implicated in the neurobiology of bulimia nervosa. Interactions between brain acetylcholine (ACh) and PYY had not been studied. Therefore, the present experiments were designed to explore the in vivo release of ACh from the hippocampus (HPC) of rats in response to hypothalamic infusion of PYY. Hippocampal ACh release was found to increase 400% in response to 10 microg PYY. In a separate experiment, blockade of the same area of the HPC with bilateral intracerebral injections of 3.5 microg scopolamine did not affect intake stimulated by intrahypothalamic injection of 4 microg PYY. Furthermore, a third experiment showed, for the first time, that PYY (2.5-10.0 microg) can elicit robust feeding when infused directly into the HPC. The significance of these findings to the activation of limbic functions such as memory, reinforcement, and obsessional processes that accompany human binge-eating syndromes is discussed.     

Retrograde amnesia for spatial information: a dissociation between intra and extramaze cues following hippocampus lesions in rats

Several recent studies have shown a flat retrograde amnesia for spatial information following lesions to the hippocampus in rats and mice. However, the results of the present investigation demonstrate that in rats that presurgically learned a spatial reference memory task based on extramaze cues, a temporally graded retrograde amnesia is evident following lesions to the hippocampus (1, 16, 32 or 64 days after learning) if two conditions are met. First, that a wide range of retention intervals is used, and second, that independent groups of rats are tested, not a single group that learns different spatial discrimination tasks at different times (expt 1). The results of expt 2 show that the hippocampus does not serve as a consolidating mechanism when the spatial task learned presurgically is based on intramaze cues. Taken together, these results indicate that the hippocampus is critical for the storage and/or retrieval of spatial reference information that was learned up to 1 month before hippocampus damage; however, in the absence of the hippocampus, efficient retention can still occur provided that the spatial knowledge was learned in a simple associative manner.     

Functional morphology and homology in the odontocete nasal complex: implications for sound generation

The site and physiologic mechanism(s) responsible for the generation of odontocete biosonar signals have eluded investigators for decades. To address these issues we subjected postmortem toothed whale heads to interrogation using medical imaging techniques. Most of the 40 specimens (from 19 species) were examined using x-ray computed tomography (CT) and/or magnetic resonance imaging (MR). Interpretation of scan images was aided by subsequent dissection of the specimens or, in one case, by cryosectioning. In all specimens we described a similar tissue complex and identified it as the hypothetical biosonar signal generator. This complex includes a small pair of fatty bursae embedded in a pair of connective tissue lips, a cartilaginous blade, a stout ligament, and an array of soft tissue air sacs. Comparing and contrasting the morphologic patterns of nasal structures across species representing every extant odontocete superfamily reveals probable homologous relationships, which suggests that all toothed whales may be making their biosonar signals by a similar mechanism.     

Refractory hypothalamic adenylate cyclase in anorectic tumor-bearing rats: implications for NPY-induced feeding

Entorhinal-dentate evoked potentials were measured in rats before and after: (1) eight electroconvulsive shock (ECS) seizures, or (2) matched handling. In animals that received ECS, evoked potentials were significantly enhanced, as evidenced by a long-lasting increase in the amplitude of the population spike. This increase in population-spike amplitude lasted for at least 3 months after the last ECS trial. No evoked-potential changes were observed in the subjects that received matched handling. These data suggest that ECS seizures produce long-lasting, perhaps permanent, changes in the brain.     

Maternal behavior in male rats: critical times for the suppressive action of androgens

The immediate and carry-over effects of scopolamine and d-amphetamine were evaluated in a free running Y-maze spontaneous alternation task. The immediate effect of scopolamine (1.0 mg/kg) or d-amphetamine (5.0 mg/kg) was to reduce alternation to chance or to levels significantly below chance (perseveration), respectively. On a second, non-drug test day alteration decreased in saline treated animals, but increased among mice which received scopolamine on Day 1. In contrast, upon retesting in the non-drug state, the performance of animals initially treated with d-amphetamine resembled that of saline treated mice. Subsequent experiments revealed that these effects could not be attributed to drug effects on peripheral mechanisms, consolidation, residual drug action or drug dissociated learning. It was concluded that the behavioral effects of scopolamine and d-amphetamine are qualitatively different. Whereas scopolamine disrupts habituation, d-amphetamine induces perseveration independently of any effects on habituation.     

Progressive neurodegeneration after intracerebroventricular kainic acid administration in rats: implications for schizophrenia?

BACKGROUND: Intracerebroventricular (ICV) administration of kainic acid to rats produces limbic-cortical neuronal damage that has been compared to the neuropathology of schizophrenia. METHODS: Groups of adult rats were administered ICV kainic acid and then assessed for neuronal loss and the expression of proteins relevant to mechanisms of neuronal damage after one and fourteen days. Neuronal loss was assessed by two-dimensional cell counting and protein expression was assessed by immunohistochemistry. RESULTS: ICV kainic acid administration was associated with both immediate (day 1) and delayed (day 14) neuronal loss in the dorsal hippocampus. The immediate injury was largely limited to the CA3 hippocampal subfield, while the delayed injury included the CA1 subfield. Multiple mechanisms of cell death appeared to be involved in the delayed neuronal loss, as evidenced by changes in the expression of glutamate receptor subunits, heat shock protein and jun protein. CONCLUSIONS: ICV kainic acid administration to adult rats produces progressive damage to limbic-cortical neurons, involving both fast and slow mechanisms of cell death. Given the evidence for clinical deterioration, cognitive deficits and hippocampal neuropathy in some cases of schizophrenia, this animal model may be relevant for hypotheses regarding mechanisms of neurodegeneration in that disorder.     

Postejaculatory quiescence in female and male rats: Consequences for sperm transport during group mating.

Studied the pattern of postejaculatory mating in the social context of a multimale–multifemale group of Sprague-Dawley rats (N?=?21), analyzing its timing and sequence from the females' as well as the males' perspective. During mating, females had a quiescent period following each ejaculation, which was comparable with the males' (a postejaculatory interval, PEI). The PEIs of both sexes were characterized by 3 behaviorally distinguishable phases: a stationary, an interactive, and a sexual phase. There was no significant sex difference in the total length of the PEI. Nonetheless, females began active sexual behavior and entered the sexual phase more quickly than males. The time course of each phase of the PEI is compared with the time course of sperm transport in the female, and the similarities and differences between the two sexes' reproductive strategies following an ejaculation are emphasized. (45 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Loss of inhibitory synapses on the soma and axon initial segment of pyramidal cells in human epileptic peritumoural neocortex: implications for epilepsy

The peritumoural neocortex removed from epileptic patients represents an important region for research because of its possible relationship to the generation, maintenance, and propagation of seizures. The peritumoural neocortex removed from an epileptic patient showing a regrowth of an anaplastic astrocytoma was examined in detail using immunocytochemistry for gamma-aminobutyric acid, glutamic acid decarboxylase, parvalbumin, nonphosphorylated neurofilament protein, glial fibrillary acidic protein, and histocompatibility antigen HLA-DR. The patterns of immunostaining were compared with the cytoarchitecture and myeloarchitecture in adjacent sections, and with the patterns of immunostaining observed in normal control neocortex. Furthermore, quantitative electron microscopy was used to compare the synaptic densities of presumptive excitatory and inhibitory synapses between regions showing different grades of cytoarchitectural and neurochemical alterations in the peritumoural neocortex, and to compare these regions with normal neocortex. A variety of changes in synaptic circuits in the peritumoural neocortex was found, but it appears that neurons within the less abnormal-looking regions were involved in altered synaptic circuits that might contribute to epileptic activity. In these regions, the most prominent change was the loss of inhibitory synapses on the soma and axon initial segment of pyramidal cells, but numerous excitatory synapses were present on their dendrites that would make these neurons hyperexcitable. However, the most abnormal regions histologically were likely a primary zone for progression of the tumour, with many surviving neurones, but which received and formed very few synapses; thus, they were probably unrelated to the initiation, maintenance, or propagation of seizures.     

Mitochondrial membrane potential and DNA stainability in human sperm cells: a flow cytometry analysis with implications for male infertility

Sperm cells from control donors of proven fertility and men from barren couples were studied by conventional procedures, i.e., light microscopy as well as flow cytometry. Light microscopy analysis of semen included the measurement of spermatozoa concentration, morphology, and motility. All the men from barren couples were asthenozoospermic at the conventional analysis of semen samples. Flow cytometry was applied to study two important parameters of sperm cells: mitochondrial membrane potential (MMP) assessed by the cationic dye JC-1 and DNA stainability with propidium iodide (PI). JC-1 staining was more reliable than the classical procedure used for this purpose, i.e., rhodamine 123 (Rh123) staining, and allowed us to show a positive correlation between MMP and spermatozoa motility. Regarding DNA analysis, a higher relative percentage of immature spermatozoa, showing a high accessibility of DNA to the intercalating PI fluorochrome, was found in men from barren couples compared to donors of proven fertility. The relative percentage of immature spermatozoa was significantly higher in semen from oligoasthenozoospermic subjects. Moreover, a positive correlation was found between immature spermatozoa, as evaluated by PI staining, and cells with depolarized mitochondria, as evaluated by JC-1 staining, suggesting that spermatozoa defective for nuclear maturity could be functionally defective cells. No correlation between immature spermatozoa determined by FCM and immature spermatozoa determined by light microscopy was found, suggesting that these two techniques assess sperm cell maturity at different levels.     

Vitamin E attenuates the development of haloperidol-induced dopaminergic hypersensitivity in rats: possible implications for tardive dyskinesia

Chronic haloperidol treatment in rats results in behavioural supersensitivity to dopamine agonists. This mechanism has been suggested as a possible animal model for tardive dyskinesia. In the present study the simultaneous administration of vitamin E to chronic haloperidol treatment in rats prevented the development of behavioural supersensitivity to apomorphine. This finding suggest that the concomitant administration of vitamin E to neuroleptics might prevent the development of tardive dyskinesia in humans.     

Testosterone has rewarding affective properties in male rats: Implications for the biological basis of sexual motivation.

Evidence from mammalian species, including humans, suggests that testosterone (TST) enhances motivational aspects of sexual behavior, although the mechanism by which TST exerts this effect is unknown. The hypothesis that increases in plasma TST have rewarding affective properties was examined. Acute elevations of plasma TST were induced in intact male rats by systemic administration of a recently developed testosterone-hydroxypropyl-β-cyclodextrin inclusion complex that mimics pulsatile release of the hormone. In a conditioned-place-preference paradigm, rats displayed a preference for an environment previously paired with TST administration (800 μg/kg and 1,200 μg/kg) as opposed to an environment paired with saline administration, indicating that TST has rewarding affective properties. The findings suggest that TST may enhance motivational aspects of mammalian sexual behavior by facilitating acquisition or expression of learned associations between environmental stimuli and sexual activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Endogenous hematopoietic reconstitution induced by human umbilical cord blood cells in immunocompromised mice: implications for adoptive therapy

Cross-linking the heterotrimeric (alpha beta gamma 2) IgE receptor, Fc epsilon RI, of mast cells activates two tyrosine kinases: Lyn, which phosphorylates beta and gamma subunit immunoreceptor tyrosine-based activation motifs, and Syk, which binds gamma-phospho-immunoreceptor tyrosine-based activation motifs and initiates cellular responses. We studied three Fc epsilon RI-dimerizing mAbs that maintain similar dispersed distributions over the surface of RBL-2H3 mast cells but elicit very different signaling responses. Specifically, mAb H10 receptor dimers induce very little inositol 1,4,5-trisphosphate synthesis, Ca2+ mobilization, secretion, spreading, ruffling, and actin plaque assembly, whereas dimers generated with the other anti-Fc epsilon RI mAbs induce responses that are only modestly lower than that to multivalent Ag. H10 receptor dimers activate Lyn and support Fc epsilon RI beta and gamma subunit phosphorylation but are poor Syk activators compared with Ag and the other anti-Fc epsilon RI mAbs. H10 receptor dimers have two other distinguishing features. First, they induce stable complexes between activated Lyn and receptor subunits. Second, the predominant Lyn-binding phospho-beta isoform found in mAb H10-treated cells is a less tyrosine phosphorylated, more electrophoretically mobile species than the predominant isoform in Ag-treated cells that does not coprecipitate with Lyn. These studies implicate Lyn dissociation from highly phosphorylated receptor subunits as a new regulatory step in the Fc epsilon RI signaling cascade required for Syk activation and signal progression.     

Minimum structural requirements for peptide presentation by major histocompatibility complex class II molecules: implications in induction of autoimmunity

The precise mechanisms of failure of immunological tolerance to self proteins are not known. Major histocompatibility complex (MHC) susceptibility alleles, the target peptides, and T cells with anti-self reactivity must be present to cause autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a murine model of a human autoimmune disease, multiple sclerosis. In EAE, residues 1-11 of myelin basic protein (MBP) are the dominant disease-inducing determinants in PL/J and (PL/J x SJL/J)F1 mice. Here we report that a six-residue peptide (five of them native) of MBP can induce EAE. Using peptide analogues of the MBP-(1-11) peptide, we demonstrate that only four native MBP residues are required to stimulate MBP-specific T cells. Therefore, this study demonstrates lower minimum structural requirements for effective antigen presentation by MHC class II molecules. Many viral and bacterial proteins share short runs of amino acid similarity with host self proteins, a phenomenon known as molecular mimicry. Since a six-residue peptide can sensitize MBP-specific T cells to cause EAE, these results define a minimum sequence identity for molecular mimicry in autoimmunity.