Somatosensory and Visual Deprivation Each Decrease the Density of Parvalbumin Neurons and Their Synapse Terminals in the Prefrontal Cortex and Hippocampus of Mice

In the phenomenon known as cross-modal plasticity, the loss of one sensory system is followed by improved functioning of other intact sensory systems. MRI and functional MRI studies suggested a role of the prefrontal cortex and the temporal lobe in cross-modal plasticity. We used a mouse model to examine the effects of sensory deprivation achieved by whisker trimming and visual deprivation achieved by dark rearing in neonatal mice on the appearance of parvalbumin (PV) neurons and the formation of glutamic acid decarboxylase 67 (GAD67)-positive puncta around pyramidal neurons in the prefrontal cortex and hippocampus. Whisker trimming, but not dark rearing, decreased the density of PV neurons in the hippocampus at postnatal day 28 (P28). In the prefrontal cortex, whisker trimming and dark rearing decreased the density of PV neurons in layer 5/6 (L5/6) at P28 and in L2/3 at P56, respectively, whereas dark rearing increased the density of PV neurons in L5/6 at P56. Whisker trimming decreased the density of GAD67-positive puncta in CA1 of the hippocampus at both P28 and P56 and in L5/6 of the prefrontal cortex at P28. Dark rearing decreased the density of GAD67-positive puncta in CA1 of the hippocampus and in both L2/3 and L5/6 of the prefrontal cortex at P28, and in L2/3 of the prefrontal cortex at P56. These results demonstrate that somatosensory or visual deprivation causes changes in the PV-interneuronal network in the mouse prefrontal cortex and hippocampus. The results also suggest that the alteration of the PV-interneuronal network, especially in the prefrontal cortex, may contribute to cross-modal plasticity

Helping-Like Behaviour in Mice Towards Conspecifics Constrained Inside Tubes

Prosocial behaviour, including helping behaviour, benefits others. Recently, helping-like behaviour has been observed in rats, but whether it is oriented towards rescue, social contact with others, or other goals remains unclear. Therefore, we investigated whether helping-like behaviour could be observed in mice similar to that in rats. Because mice are social animals widely used in neuroscience, the discovery of helping-like behaviour in mice would be valuable in clarifying the psychological and biological mechanisms underlying pro-sociability. We constrained mice inside tubes. Subject mice were allowed to move freely in cages with tubes containing constrained conspecifics. The subject mice released both cagemates and stranger mice but did not engage in opening empty tubes. Furthermore, the same behaviour was observed under aversive conditions and with anesthetised conspecifics. Interestingly, hungry mice opened the tubes containing food before engaging in tube-opening behaviour to free constrained conspecifics. Mice showed equal preferences for constrained and freely moving conspecifics. We demonstrated for the first time that mice show tube-opening behaviour. Furthermore, we partly clarified the purpose and motivation of this behaviour. An effective mouse model for helping-like behaviour would facilitate research on the mechanisms underlying prosocial behaviour

Attenuated Sensory Deprivation-induced Changes of Parvalbumin Neuron Density in the Barrel Cortex of FcγRllB-deficient Mice

Recent studies have demonstrated the important role of immune molecules in the development of neuronal circuitry and synaptic plasticity. We have detected the presence of FcγRllB protein in parvalbumin- containing inhibitory interneurons (PV neurons). In the present study, we examined the appearance of PV neurons in the barrel cortex and the effect of sensory deprivation in FcγRllB-deficient mice (FcγRllB-/-) and wild-type mice. There was no substantial difference in the appearance of PV neurons in the developing barrel cortex between FcγRllB-/- and wild-type mice. Sensory deprivation from immediately after birth (P0) or P7 to P12-P14 induced an increase in PV neurons. In contrast, sensory deprivation from P7 or P14 to P28, but not from P21 to P28, decreased PV neurons in wild-type mice. However, sensory deprivation from P0 or P7 to P12-P14 did not increase PV neurons and sensory deprivation from P7 or P14 to P28 did not decrease or only modestly decreased PV neurons in FcγRllB-/- mice. The results indicate that expression of PV is regulated by sensory experience and the second and third postnatal weeks are a sensitive period for sensory deprivation, and suggest that FcγRllB contributes to sensory experience-regulated expression of PV

Layer-specific expression of extracellular matrix molecules in the mouse somatosensory and piriform cortices

In the developing central nervous system (CNS), extracellular matrix (ECM) molecules have regulating roles such as in brain development, neural-circuit maturation, and synaptic-function control. However, excluding the perineuronal net (PNN) area, the distribution, constituent elements, and expression level of granular ECM molecules (diffuse ECM) present in the mature CNS remain unclear. Diffuse ECM molecules in the CNS share the components of PNNs and are likely functional. As cortical functions are greatly region-dependent, we hypothesized that ECM molecules would differ in distribution, expression level, and components in a region- and layer-dependent manner. We examined the layer-specific expression of several chondroitin sulfate proteoglycans (aggrecan, neurocan, and brevican), tenascin-R, Wisteria floribunda agglutinin (WFA)-positive molecules, hyaluronic acid, and link protein in the somatosensory and piriform cortices of mature mice. Furthermore, we investigated expression changes in WFA-positive molecules due to aging. In the somatosensory cortex, PNN density was particularly high at layer 4 (L4), but not all diffuse ECM molecules were highly expressed at L4 compared to the other layers. There was almost no change in tenascin-R and hyaluronic acid in any somatosensory-cortex layer. Neurocan showed high expression in L1 of the somatosensory cortex. In the piriform cortex, many ECM molecules showed higher expression in L1 than in the other layers. However, hyaluronic acid showed high expression in deep layers. Here, we clarified that ECM molecules differ in constituent elements and expression in a region- and layer-dependent manner. Region-specific expression of ECM molecules is possibly related to functions such as region-specific plasticity and vulnerability

Expression and localization of connective tissue growth factor (CTGF/Hcs24/CCN2) in osteoarthritic cartilage

AbstractObjectiveThe investigation of the expression and localization of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24/CCN family member 2 (CTGF/Hcs24/CCN2) in normal and osteoarthritic (OA) cartilage, and quantification of CTGF/Hcs24-positive cells.MethodsCartilage samples of patients (n=20) with late stage OA were obtained at total joint replacement surgery. Morphologically normal cartilage was harvested for comparison purposes from the femoral heads of 6 other patients with femoral neck fracture. Paraffin-embedded sections were stained by Safranin O. The severity of the OA lesions was divided into four stages (normal, early, moderate, and severe). The localization of protein and mRNA for CTGF/Hcs24 was investigated by immunohistochemistry and in situ hybridization, respectively. The population of CTGF/Hcs24-positive chondrocytes in OA cartilage and chondro-osteophyte was quantified by counting the number of the cells under light microscopy.ResultsSignals for CTGF/Hcs24 were detected in a small percentage of chondrocytes throughout the layers of normal cartilage. In early stage OA cartilage, the CTGF/Hcs24-positive chondrocytes were localized mainly in the superficial layer. In moderate to severe OA cartilage, intense staining for CTGF/Hcs24 was observed in proliferating chondrocytes forming cell clusters next to the cartilage surface. In chondro-osteophyte, strong signals were found in the chondrocytes of the proliferative and hypertrophic zones.ConclusionCTGF/Hcs24 expression was detected in both normal and OA chondrocytes of human samples. The results of the current study suggested that expression of CTGF/Hcs24 was concomitant with development of OA lesions and chondrocyte differentiation in chondro-osteophyte

Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy

Understanding the molecular and cellular mechanisms involved during the onset of epilepsy is crucial for elucidating the overall mechanism of epileptogenesis and therapeutic strategies. Previous studies, using a pentylenetetrazole (PTZ)-induced kindling mouse model, showed that astrocyte activation and an increase in perineuronal nets (PNNs) and extracellular matrix (ECM) molecules occurred within the hippocampus. However, the mechanisms of initiation and suppression of these changes, remain unclear. Herein, we analyzed the attenuation of astrocyte activation caused by dizocilpine (MK-801) administration, as well as the anticonvulsant effect of α-pinene on seizures and production of ECM molecules. Our results showed that MK-801 significantly reduced kindling acquisition, while α-pinene treatment prevented an increase in seizures incidences. Both MK-801 and α-pinene administration attenuated astrocyte activation by PTZ and significantly attenuated the increase in ECM molecules. Our results indicate that astrocyte activation and an increase in ECM may contribute to epileptogenesis and suggest that MK-801 and α-pinene may prevent epileptic seizures by suppressing astrocyte activation and ECM molecule production

Anti-stress effects of the hydroalcoholic extract of Rosa gallica officinalis in mice

Rosa gallica, a plant of the Rosa genus, has been used widely since the 13th century and is cultivated in many areas as a medicinal plant for the preparation of herbal medicines. However, details of the neuropsychological effects of R. gallica remain unclear; therefore we aimed to investigate the neuropsychological effects of a water-soluble extract of R. gallica in male C57BL/6N mice under normal conditions and under chronic stress. We administered a water-soluble extract of R. gallica to mice and performed a series of behavioral experiments to compare the treated animals with the untreated controls. No significant differences in activity level, anxiety-like behavior, depression-like behavior, body weight, and body temperature were observed between R. gallica-treated mice and control mice. However, in mice subjected to chronic stress, the observed decrease in activity was smaller in the R. gallica-treated mice than in the control mice. The oral administration of R. gallica did not affect the normal behavior of mice. However, when the mice were subjected to stress, R. gallica exerted an anti-stress effect. Therefore, R. gallica has potential as a medicinal plant for the purpose of stress prevention

Comprehensive behavioral study of the effects of vanillin inhalation in mice

Vanillin is widely used in food and cosmetics, among other substances, for its sweet smell. However, the neuropsychological effects of vanillin inhalation have not been elucidated. In this study, we investigated the effect of vanillin inhalation on mouse behavior. First, we investigated whether the aroma of vanillin was attractive or repulsive for mice. Thereafter, the mice inhaled vanillin for 20 min before each test in a series of behavioral tests (elevated plus maze, open field, Y-maze, tail suspension, cotton bud biting, and Porsolt forced swim tests). In these tests, the mice showed a neutral response to vanillin. Mice that inhaled vanillin had a suppressed pain response in the hot plate test. In addition, the grip strength of the forelimbs of mice that inhaled vanillin was decreased. No significant differences were found between the mice inhaling vanillin and control mice in the open field, Y-maze, tail suspension, forced swimming, and aggression tests. These results show that vanillin inhalation has anti-nociceptive effects, similar to other routes of administration. The results also show that vanillin inhalation does not cause significant behavioral effects

Behavioural effects of inhalation exposure to dizocilpine (MK-801) in mice

The complex pathophysiology of brain disorders and the difficulty of delivering therapeutic agents to the brain remain major obstacles in the research and development of new therapeutic methods for brain disorders. Therefore, delivering existing therapeutic agents to the central nervous system is expected to provide benefits in various diseases. In this study, we investigated whether inhaled central nervous system drugs reached the brain and affected mouse behaviour. Dizocilpine (MK-801), which increases locomotor activity in mice, was mainly used to study this hypothesis. First, we administered MK-801, an N-methyl-d-aspartate receptor antagonist, to mice via inhalation and examined whether it induced excessive activity similar to that observed after intraperitoneal administration. We also examined the time- and dose-dependency of drug induced changes in mouse behaviour after MK-801 inhalation. Next, we investigated whether inhalation of scopolamine, pentobarbital, and imipramine also affected mouse behaviour. Mice that inhaled MK-801 showed MK-801–induced hyperactivity similar to that observed following intraperitoneal administration. Furthermore, the extent of activity changed in a time- and dose-dependent manner after MK-801 inhalation. Inhalation of pentobarbital, scopolamine, and imipramine also changed mouse behaviour. These results demonstrate that inhalation of MK-801 exerts effects similar to those achieved with intraperitoneal and oral administration in mice. Thus, central nervous system agonists can reach the brain efficiently via inhalation. This finding may facilitate the development of improved therapies for brain disorders

Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex

Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC) in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28) or P58 on the density of parvalbumin (PV), calbindin (CB), and calretinin (CR) neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6). Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity