Caloric restriction and aging but not overexpression of SOD1 affect hippocampal volumes in mice

Caloric restriction (CR) and antioxidants have been proposed as strategies to attenuate age-related brain changes. The hippocampus and its subregions dentate gyrus (DG), CA3 and CA1-2 show vulnerability to aging, with hippocampal volume alterations as a measurable sign. Using design-based stereological techniques, we investigated the volumes of the hippocampus and its subregions in six 12-month-old and six 24-month-old mice that were randomly selected from four aging cohorts of 60 male mice each: (1) wild-type mice (WT) fed with control diet (CD), (2) transgenic mice oxerexpressing normal human SOD1 fed with CD, (3) WT mice fed with CR diet, and (4) SOD1 mice fed with CR diet. Aging reduced the mean volume of the entire hippocampus (−9.5%), grey (−8.7%) and white matter (−9.7%), and CA3 subregion (−13.6%), but not DG or CA1-2 subregion. CR reduced the mean volumes of every hippocampal region investigated (on average −11%) in both 12-month-old, and 24-month-old mice. Overexpression of SOD1 was not associated with any volume alteration. These findings indicate that although aging and CR in mice are both associated with hippocampal volume reductions, the patterns of the volume reductions differ. These morphometric alterations may have impact on the function of the hippocampus during aging and CR.     

Limitations in transplantation of astroglia-biomatrix bridges to stimulate corticospinal axon regrowth across large spinal lesion gaps

Regrowth of injured axons across rather small spinal cord lesion gaps and subsequent functional recovery has been obtained after many interventions. Long-distance regeneration of injured axons across clinically relevant large spinal lesion gaps is relatively unexplored. Here, we aimed at stimulating long-distance regrowth of the injured corticospinal (CS) tract. During development, an oriented framework of immature astrocytes is important for correct CS axon outgrowth. Furthermore, a continuous growth promoting substrate may be needed to maintain a CS axon regrowth response across relatively large spinal lesion gaps. Hence, we acutely transplanted poly(d,l)-lactide matrices, which after seeded with immature astrocytes render aligned astrocyte-biomatrix complexes (R. Deumens, et al. Alignment of glial cells stimulates directional neurite growth of CNS neurons in vitro. Neuroscience 125 (3) (2004) 591–604), into 2-mm long dorsal hemisection lesion gaps. In order to create a growth promoting continuum, astrocyte suspensions were also injected rostral and caudal to the lesion gap. During 2 months, locomotion was continuously monitored. Histological analysis showed that astrocytes injected into host spinal tissue survived, but did not migrate. None of the astrocytes on the biomatrices survived within the lesion gap. BDA-labeled CS axons did not penetrate the graft. However, directly rostral to the lesion gap, 120.9 ± 38.5% of the BDA-labeled CS axons were present in contrast to 12.8 ± 3.9% in untreated control animals. The observed anatomical changes were not accompanied by locomotor improvements as analyzed with the BBB and CatWalk. We conclude that although multifactorial strategies may be needed to stimulate long-distance CS axon regrowth, future studies should focus on enhancing the viability of cell/biomatrix complexes within large spinal lesion gaps.     

The PDE5 inhibitor vardenafil does not affect auditory sensory gating in rats and humans

Rationale

Sensory gating is an adaptive mechanism of the brain to prevent overstimulation. Patients suffering from clinical disorders such as Alzheimer’s disease or schizophrenia exhibit a deficit in gating, which indicates not only an impairment in basic information processing that might contribute to the cognitive problems seen in these patients. Phosphodiesterase type 5 inhibitors (PDE5-Is) have been shown to improve cognition in rodents in various behavioural tasks and might consequently be an interesting target for cognition enhancement. However, the effects of PDE5-Is on sensory gating are not known yet.

Objectives

This work aims to study the effects of PDE5 inhibition on auditory sensory gating in rats and humans.

Methods

In the rat study, vehicle or 0.3–3 mg/kg of the PDE5-I vardenafil was given orally 30 min before testing and electrode locations were the vertex, hippocampus and the striatum. The human subjects received placebo, 10–20 mg vardenafil 85 min before testing and sensory gating was measured at the cortex (Fz, Fcz and Cz) electrodes.

Results

Significant gating was only found for the N1 component in rats while all three peaks P1, N1 and P2 showed gating in humans, i.e. the response to the second sound click was decreased as compared with the first for these deflections. Administration of vardenafil did neither have an effect on sensory gating in rats nor in humans.

Conclusions

These findings imply that positive effects of PDE5 inhibition on cognition are not mediated by more early phases of information processing.     

急性重度有机磷农药中毒32例的救治

0引言在急性重度有机磷农药中毒(AOPP)救治过程中,早期的内科常规处理,结合抗胆碱药及复能剂的应用,并积极进行肠道水疗,血液灌流,后期营养支持等综合救治,能提高AOPP在基层医院的抢救成功率、存活率.我院2000-3/2005-03收治32例重度AOPP患者,获得满意治疗效果.     

Object recognition testing: statistical considerations

In Parkinson's disease both limb and cranial sensorimotor functions are impaired, leading to a profound diminished quality of life for many patients. Toxin and genetic animal models of Parkinson's disease are likely essential for understanding the pathology associated with these impairments as well as for the development and testing of potential therapeutics. Here we describe useful novel and established behavioral outcome measures for assessing limb and cranial sensorimotor functions in toxin and genetic models of parkinsonism in rats and mice.     

Increased Number of Cerebellar Granule Cells and Astrocytes in the Internal Granule Layer in Sheep Following Prenatal Intra-amniotic Injection of Lipopolysaccharide

Chorioamnionitis is an important problem in perinatology today, leading to brain injury and neurological handicaps. However, there are almost no data available regarding chorioamnionitis and a specific damage of the cerebellum. Therefore, this study aimed at determining if chorioamnionitis causes cerebellar morphological alterations. Chorioamnionitis was induced in sheep by the intra-amniotic injection of lipopolysaccharide (LPS) at a gestational age (GA) of 110 days. At a GA of 140 days, we assessed the mean total and layer-specific volume and the mean total granule cell (GCs) and Purkinje cell (PC) number in the cerebelli of LPS-exposed and control animals using high-precision design-based stereology. Astrogliosis was assessed in the gray and white matter (WM) using a glial fibrillary acidic protein staining combined with gray value image analysis. The present study showed an unchanged volume of the total cerebellum as well as the molecular layer, outer and inner granular cell layers (OGL and IGL, respectively), and WM. Interestingly, compared with controls, the LPS-exposed brains showed a statistically significant increase (+20.4%) in the mean total number of GCs, whereas the number of PCs did not show any difference between the two groups. In addition, LPS-exposed animals showed signs of astrogliosis specifically affecting the IGL. Intra-amniotic injection of LPS causes morphological changes in the cerebellum of fetal sheep still detectable at full-term birth. In this study, changes were restricted to the inner granule layer. These cerebellar changes might correspond to some of the motor or non-motor deficits seen in neonates from compromised pregnancies.     

Dopaminergic transmission in the rat retina: evidence for volume transmission

The study was designed to determine whether dopaminergic neurotransmission in the retina can operate via volume transmission. In double immunolabelling experiments, a mismatch as well as a match was demonstrated in the rat retina between tyrosine hydroxylase (TH) and dopamine (DA) immunoreactive (ir) terminals and cell bodies and dopamine D2 receptor-like ir cell bodies and processes. The match regions were located in the inner nuclear and plexiform layers (D2 ir cell bodies plus processes). The mismatch regions were located in the ganglion cell layer, the outer plexiform layer, and the outer segment of the photoreceptor layer, where very few TH ir terminals can be found in relation to the D2 like ir processes. In similar experiments analyzing D1 receptor like ir processes versus TH ir nerve terminals, mainly a mismatch in their distribution could be demonstrated, with the D1 like ir processes present in the outer plexiform layer and the outer segment where a mismatch in D2 like receptors also exists. The demonstration of a mismatch between the localization of the TH terminal plexus and the dopamine D2 and D1 receptor subtypes in the outer plexiform layer, the outer segment and the ganglion cell layer (only D2 immunoreactivity (IR)) suggests that dopamine, mainly from the inner plexiform layer, may reach the D2 and D1 mismatch receptors via diffusion in the extracellular space. After injecting dopamine into the corpus vitreum, dopamine diffuses through the retina, and strong catecholamine (CA) fluorescence appears in the entire inner plexiform layer and the entire outer plexiform layer, representing the match and mismatch DA receptor areas, respectively. The DA is probably bound to D1 and D2 receptors in both plexiform layers, since the DA receptor antagonist chlorpromazine fully blocks the appearance of the DA fluorescence, while only a partial blockade is found after haloperidol treatment which mainly blocks D2 receptors. These results indicate that the amacrine and/or interplexiform DA cells, with sparse branches in the outer plexiform layer, can operate via volume transmission in the rat retina to influence the outer plexiform layer and the outer segment, as well as other layers of the rat retina such as the ganglion cell layer.     

Delivery of normal twins following the intracytoplasmic injection of spermatozoa from a patient with 47,XXY Klinefelter's syndrome

Klinefelter's syndrome is a disorder of gonadal development and typically reveals a 47,XXY karyotype although mosaic forms also occur. Azoospermia is a common feature, but severe oligozoospermia and fertility have been reported. In this study, we have used intracytoplasmic sperm injection (ICSI) to achieve a live twin birth using spermatozoa from a 47,XXY man who has occasional spermatozoa present in the ejaculate. Spermatozoa were obtained from multiple ejaculates and frozen prior to commencing IVF treatment. Nine good quality embryos developed from the injection of 13 oocytes. All nine embryos were frozen. The initial transfer of two frozen-thawed embryos was unsuccessful. In the following cycle, the transfer of two additional frozen-thawed embryos resulted in the delivery of normal, healthy male and female twins. Five embryos remain frozen. It has generally been thought that the germ cells of 47,XXY men are unable to proceed through meiosis. Any spermatozoa produced have been assumed to come from a normal germ cell and therefore likely to have a normal karyotype. However, recent evidence suggests that meiosis of 47,XXY germ cells may be possible. Whether spermatozoa in these men arise from meiosis of 47,XXY germ cells, or from germ cells which have attained a normal karyotype by loss of an X chromosome, is unclear. Any risks in using spermatozoa from these patients have not yet been established. Patients need to be advised accordingly, and preimplantation or prenatal diagnosis should be considered. A cautious approach to the treatment of these patients is therefore warranted.