ALBERT

Description:    Immunohistochemistry for transient receptor potential melastatin-8 (TRPM8), the cold and menthol receptor, was performed on the rat soft palate, epiglottis and pharynx. TRPM8-immunoreactive (IR) nerve fibers were located beneath the mucous epithelium, and occasionally penetrated the epithelium. These nerve fibers were abundant in the posterior portion of the soft palate and at the border region of naso-oral and laryngeal parts of the pharynx. The epiglottis was free from such nerve fibers. The double immunofluorescence method demonstrated that TRPM8-IR nerve fibers in the pharynx and soft palate were mostly devoid of calcitonin gene-related peptide-immunoreactivity (CGRP-IR). The retrograde tracing method also demonstrated that 30.1 and 8.7 % of sensory neurons in the jugular and petrosal ganglia innervating the pharynx contained TRPM8-IR, respectively. Among these neurons, the co-expression of TRPM8 and CGRP-IR was very rare. In the nodose ganglion, however, pharyngeal neurons were devoid of TRPM8-IR. Taste bud-like structures in the soft palate and pharynx contained 4–9 TRPM8-IR cells. In the epiglottis, the mucous epithelium on the laryngeal side had numerous TRPM8-IR cells. The present study suggests that TRPM8 can respond to cold stimulation when food and drinks pass through oral and pharyngeal cavities. Content Type Journal Article Category Short Communication Pages 1-5 DOI 10.1007/s10571-012-9888-1 Authors Tadasu Sato, Division of Oral and Craniofacial Anatomy, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Sendai, 980-8575 Japan Masatoshi Fujita, Division of Oral and Craniofacial Anatomy, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Sendai, 980-8575 Japan Mitsuhiro Kano, Division of Oral and Craniofacial Anatomy, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Sendai, 980-8575 Japan Hiroshi Hosokawa, Division of Biological Information, Department of Intelligence Science and Technology, Graduate School of Informatics, Kyoto University, Yoshida-honmachi, Sakyo-ku, Kyoto, 606-8501 Japan Teruyoshi Kondo, Department of Clinical Engineering, Kyushu University of Health and Welfare School of Health Science, Yoshinomachi 1714.1, Nobeoka, Japan Toshihiko Suzuki, Division of Oral and Craniofacial Anatomy, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Sendai, 980-8575 Japan Eriko Kasahara, Division of Oral Diagnosis, Graduate School of Dentistry, Tohoku University, Sendai, 980-8575 Japan Noriaki Shoji, Division of Oral Diagnosis, Graduate School of Dentistry, Tohoku University, Sendai, 980-8575 Japan Takashi Sasano, Division of Oral Diagnosis, Graduate School of Dentistry, Tohoku University, Sendai, 980-8575 Japan Hiroyuki Ichikawa, Division of Oral and Craniofacial Anatomy, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Sendai, 980-8575 Japan Journal Cellular and Molecular Neurobiology Online ISSN 1573-6830 Print ISSN 0272-4340

Description:    p300 and its homolog cyclic AMP response element binding protein (CBP) are coactivators that were identified to participate in many biological processes including neural development and cognition. Their roles within the rodent spinal cord have not been reported systematically; in this study, their spatiotemporal distribution in the spinal cord of adult rat following chronic constriction injury (CCI) was studied. p300 and CBP expressed predominantly in nuclei in the gray matter of rat spinal cord. Rats undergoing CCI surgery showed increased p300/CBP immunoreactivity (IR) compared with normal control and sham-operated rats. The number of IR cells reached the peak at day 14 following CCI compared with those on day 3, 7, and 21, accompanied with significant behavioral changes of neuropathic pain. Cell-type determination by immunofluorescence at day 14 following CCI revealed that p300 and CBP expressed in neurons, but not in astrocytes or microglial cells. These results suggest that p300 and CBP are probably involved in the maintenance of neuropathic pain on spinal cord level. Furthermore, p300 and CBP may serve as a sensor only in neurons but not in astrocytes or microglia cells in the adult rat spinal cord. Content Type Journal Article Category Original Research Pages 1-8 DOI 10.1007/s10571-012-9885-4 Authors Xiao-Yan Zhu, Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008 Hunan, China Chang-Sheng Huang, Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008 Hunan, China Qian Li, Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008 Hunan, China Qu-Lian Guo, Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008 Hunan, China Ying Wang, Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008 Hunan, China Xin He, Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008 Hunan, China Juan Liao, Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008 Hunan, China Journal Cellular and Molecular Neurobiology Online ISSN 1573-6830 Print ISSN 0272-4340

Description:    As a novel cell cycle protein, Spy1 enhances cell proliferation, promotes the G1/S transition as well as inhibits apoptosis in response to UV irradiation. Spy1 levels are tightly regulated during mammary development, and overexpression of Spy1 accelerates tumorigenesis in vivo. But little is known about the role of Spy1 in the pathological process of damage and regeneration of the peripheral nervous system. Here we established a rat sciatic nerve crush (SNC) model to examine the spatiotemporal expression of Spy1. Spy1 expression was elevated gradually after sciatic nerve crush and peaked at day 3. The alteration was due to the increased expression of Spy1 in axons and Schwann cells after SNC. Spy1 expression correlated closely with Schwann cells proliferation in sciatic nerve post injury. Furthermore, Spy1 largely localized in axons in the crushed segment, but rarely co-localized with GAP43. These findings suggested that Spy1 participated in the pathological process response to sciatic nerve injury and may be associated with Schwann cells proliferation and axons regeneration. Content Type Journal Article Category Original Research Pages 1-9 DOI 10.1007/s10571-012-9887-2 Authors Jianhua Cao, Department of Orthopaedics, Affiliated Mental Health Center of Nantong University, Nantong, 226001 People’s Republic of China Jiao Yang, Department of Immunology, Medical College, Nantong University, Nantong, 226001 Jiangsu, People’s Republic of China Youhua Wang, Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001 People’s Republic of China Jian Xu, Department of Orthopaedics, Affiliated Mental Health Center of Nantong University, Nantong, 226001 People’s Republic of China Zhengming Zhou, Department of Immunology, Medical College, Nantong University, Nantong, 226001 Jiangsu, People’s Republic of China Chun Cheng, Department of Immunology, Medical College, Nantong University, Nantong, 226001 Jiangsu, People’s Republic of China Xiaojuan Liu, Department of Pathogenbiology, Medical College, Nantong University, Nantong, 226001 Jiangsu, People’s Republic of China Xinghai Cheng, Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001 People’s Republic of China Long Long, Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001 People’s Republic of China Xingxing Gu, The Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, 19 Qi-Xiu Road, Nantong, 226001 Jiangsu, People’s Republic of China Journal Cellular and Molecular Neurobiology Online ISSN 1573-6830 Print ISSN 0272-4340

Description:    To evaluate the function of rat mesenchymal stem cells (rMSCs) on denervated gastrocnemius muscles and to address the role of ciliary neurotrophic factor (CNTF) in rMSCs, denervated Wistar rats were separately injected with culture media (sham control), CNTF protein, 2.5 × 10 5 siCNTF-treated rMSCs, 2.5 × 10 5 GFP-transfected rMSCs, or 2.5 × 10 5 untreated rMSCs. Muscle function was assessed at different time points post-surgery. Tibial nerve and gastrocnemius muscle samples were taken at 4, 8, and 12 weeks for histochemistry, and neuromuscular junction repair was also examined by electron microscopy. Fluorescence immunocytochemistry on tissue sections confirmed neurotrophin expression in rMSCs but with little evidence of neuronal differentiation. The engraftment of rMSCs significantly preserved the function of denervated gastrocnemius muscle based both on evaluation of muscle function and direct examination of muscle tissue. Further, the density and depth of the junctional folds were visibly reduced 12 weeks after surgery and transplantation, especially in control group. Knockdown of CNTF expression in rMSCs failed to block muscle preservation, although administration of CNTF protein alone inhibited muscle atrophy, which indicating that delivery of rMSCs could preserve gastrocnemius muscle function following denervation and post-junctional mechanisms involved in the repairing capability of rMSCs. Content Type Journal Article Category Original Research Pages 1-12 DOI 10.1007/s10571-012-9853-z Authors Junjian Jiang, Department of Hand Surgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040 China Ping Yao, Department of Hand Surgery, Hang Zhou Plastic Surgery Hospital, Hangzhou, 310014 China Yudong Gu, Department of Hand Surgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040 China Lei Xu, Department of Hand Surgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040 China Jianguang Xu, Department of Hand Surgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040 China Haitao Tan, Orthopedics Department, The Eight Affiliated Hospital of Guangxi Medical University, No. 1 Zhongshan Middle Road, Guigang, 537100 China Journal Cellular and Molecular Neurobiology Online ISSN 1573-6830 Print ISSN 0272-4340

Description:    Previous studies have suggested that serotonergic neurons in the midbrain raphe complex have a functional topographic organization. Recent studies suggest that stimulation of a bed nucleus of the stria terminalis-dorsal raphe nucleus pathway by stress- and anxiety-related stimuli modulates a subpopulation of serotonergic neurons in the dorsal part of the dorsal raphe nucleus (DRD) and caudal part of the dorsal raphe nucleus (DRC) that participates in facilitation of anxiety-like responses. In contrast, recent studies suggest that activation of a spinoparabrachial pathway by peripheral thermal or immune stimuli excites subpopulations of serotonergic neurons in the ventrolateral part of the dorsal raphe nucleus/ventrolateral periaqueducal gray (DRVL/VLPAG) region and interfascicular part of the dorsal raphe nucleus (DRI). Studies support a role for serotonergic neurons in the DRVL/VLPAG in inhibition of panic-like responses, and serotonergic neurons in the DRI in antidepressant-like effects. Thus, data suggest that while some subpopulations of serotonergic neurons in the dorsal raphe nucleus play a role in facilitation of anxiety-like responses, others play a role in inhibition of anxiety- or panic-like responses, while others play a role in antidepressant-like effects. Understanding the anatomical and functional properties of these distinct serotonergic systems may lead to novel therapeutic strategies for the prevention and/or treatment of affective and anxiety disorders. In this review, we describe the anatomical and functional properties of subpopulations of serotonergic neurons in the dorsal raphe nucleus, with a focus on those implicated in symptoms of anxiety and affective disorders, the DRD/DRC, DRVL/VLPAG, and DRI. Content Type Journal Article Category Original Paper Pages 1-14 DOI 10.1007/s10571-012-9827-1 Authors Matthew W. Hale, School of Psychological Science, La Trobe University, Melbourne, 3086 Australia Anantha Shekhar, Department of Psychiatry and Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA Christopher A. Lowry, Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA Journal Cellular and Molecular Neurobiology Online ISSN 1573-6830 Print ISSN 0272-4340

Description:    Wnt/β-catenin signaling has a well-established role in the development of the central nervous system (CNS), and recent evidence is extending this role to include the regulation of adult hippocampal function, including neurogenesis within the dentate gyrus. While the neuroanatomical expression pattern of many canonical Wnt signaling components have been investigated, the sites of signal integration and functional downstream β-catenin activation remain comparatively less characterized in the adult CNS. Using two independent transgenic β-catenin-activated LacZ reporter mouse lines (BatGal and ins-TopGal), we demonstrate that Wnt/β-catenin signaling is active in discrete regions of the adult mouse CNS. Intriguingly, BatGal mice exhibit a broad pattern of reporter expression in the CNS, while expression in ins-TopGal mice is more restricted. Further investigation of these two lines reveals temporal differences in β-catenin-activated reporter expression during neurogenesis within the adult hippocampus. Ins-TopGal mice display peaks of Wnt/β-catenin-activated reporter expression during early and later stages of neurogenesis suggesting Wnt/β-catenin signaling plays an important role during both progenitor cell amplification as well as neuronal maturation, integration, and/or maintenance; however, results from BatGal mice are not as convincing. Thus our data using ins-TopGal mice are consistent with the idea that Wnt signaling plays diverse roles during adult hippocampal neurogenesis and support the idea that multiple transgenic reporter lines must be rigorously compared during scientific investigations. Content Type Journal Article Category Original Research Pages 1-16 DOI 10.1007/s10571-012-9841-3 Authors David S. Garbe, Pfizer Neuroscience, Pfizer, Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA Robert H. Ring, Pfizer Neuroscience, Pfizer, Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA Journal Cellular and Molecular Neurobiology Online ISSN 1573-6830 Print ISSN 0272-4340

Description:    Adeno-associated virus vector plasmid carrying the expression cassette of brain-derived neurotrophic factor (BDNF), pAAV-BDNF, was constructed and packaged into recombinant adeno-associated virus (rAAV-BDNF). The rAAV-BDNF was intravitreally injected into streptzotocin (STZ)-induced diabetic Sprague–Dawley (SD) Rats. Data showed that over-expression of BDNF could increase alive retinal ganglion cell (RGC) number and improve its function in streptzotocin(STZ)-induced diabetic rats, which might be a new method to treat diabetic neuropathy and retinopathy. Content Type Journal Article Category Original Research Pages 467-475 DOI 10.1007/s10571-011-9779-x Authors Yan Gong, Department of Ophthalmology, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, 100853 Beijing, China Zhan-Ping Chang, Department of Pathology, Aerospace 731 Hospital, Beijing, China Ruo-Tong Ren, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China Shi-hui Wei, Department of Ophthalmology, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, 100853 Beijing, China Huan-Fen Zhou, Department of Ophthalmology, The First Affiliated Hospital of General Hospital of PLA, Beijing, China Xiao-fei Chen, Department of Ophthalmology, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, 100853 Beijing, China Bao-ke Hou, Department of Ophthalmology, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, 100853 Beijing, China Xin Jin, Department of Ophthalmology, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, 100853 Beijing, China Mao-nian Zhang, Department of Ophthalmology, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, 100853 Beijing, China Journal Cellular and Molecular Neurobiology Online ISSN 1573-6830 Print ISSN 0272-4340 Journal Volume Volume 32 Journal Issue Volume 32, Number 3

Description:    Changes in gene expression of the brain serotonin (5-HT) 1A receptors may be important for the development and ameliorating depression, however identification of specific stimuli that activate or reduce the receptor transcriptional activity is far from complete. In the present study, the forced swim test (FST) exposure, the first stress session of which is already sufficient to induce behavioral despair in rats, significantly increased 5-HT1A receptor mRNA levels in the brainstem, frontal cortex, and hippocampus at 24 h. In the brainstem and frontal cortex, the elevation in the receptor gene expression after the second forced swim session was not affected following chronic administration of fluoxetine, while in the cortex, both control and FST values were significantly reduced in fluoxetine-treated rats. In contrast to untreated rats, no increase in hippocampal 5-HT1A receptor mRNA was observed in response to FST in rats chronically treated with fluoxetine. Metabolism of 5-HT (5-HIAA/5-HT) in the brainstem was significantly decreased by fluoxetine and further reduced by swim stress, showing a certain degree of independence of these changes on 5-HT1A receptor gene expression that was increased in this brain region only after the FST, but not after fluoxetine. FST exposure also decreased the brainstem dopamine metabolism, which was unexpectedly positively correlated with 5-HT1A receptor mRNA levels in the frontal cortex. Together, these data suggest that the effects of the forced swim stress as well as fluoxetine involve brain region-dependent alterations in 5-HT1A receptor gene transcription, some of which may be interrelated with concomitant changes in catecholamine metabolism. Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s10571-012-9828-0 Authors G. T. Shishkina, Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Russian Academy of Science, Novosibirsk, Russia 630090 T. S. Kalinina, Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Russian Academy of Science, Novosibirsk, Russia 630090 N. N. Dygalo, Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Russian Academy of Science, Novosibirsk, Russia 630090 Journal Cellular and Molecular Neurobiology Online ISSN 1573-6830 Print ISSN 0272-4340

Description:    Since gonadal female hormones act on and protect neurons, it is well known that the female brain is less vulnerable to stroke or other brain insults than the male brain. Although glial functions have been shown to affect the vulnerability of the brain, little is known if such a sex difference exists in glia, much less the mechanism that might cause gender-dependent differences in glial functions. In this study, we show that in vitro astrocytes obtained from either female or male pups show a gonadal hormone-independent phenotype that could explain the gender-dependent vulnerability of the brain. Female spinal astrocytes cleared more glutamate by GLAST than male ones. In addition, motoneurons seeded on female spinal astrocytes were less vulnerable to glutamate than those seeded on male ones. It is suggested that female astrocytes uptake more glutamate and reveal a stronger neuroprotective effect against glutamate than male ones. It should be noted that such an effect was independent of gonadal female hormones, suggesting that astrocytes have cell-autonomous regulatory mechanisms by which they transform themselves into appropriate phenotypes. Content Type Journal Article Category Short Communication Pages 1-4 DOI 10.1007/s10571-012-9829-z Authors Yosuke Morizawa, Department of Neuropharmacology, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan Kaoru Sato, Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan Junpei Takaki, Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan Asami Kawasaki, Center for Trans-Disciplinary Research, Niigata University, Niigata, Japan Keisuke Shibata, Department of Neuropharmacology, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan Takeshi Suzuki, Division of Basic Biological Sciences, Keio University, Tokyo, Japan Shigeru Ohta, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Schuichi Koizumi, Department of Neuropharmacology, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan Journal Cellular and Molecular Neurobiology Online ISSN 1573-6830 Print ISSN 0272-4340

Description:    Compelling evidence shows that the offspring subjected to uncontrolled hyperlycemia during gestation display behavioral, neurochemical, and cellular abnormalities during adulthood. However, the molecular mechanisms underlying these defects remain elusive. Previous studies have shown an increased rate of apoptosis and a decreased index of neuronal proliferation associated with diabetic embryopathy. The aim of the present study was to determine whether impairments in apoptotic related proteins also occur in the developing central nervous system from non-malformed embryos exposed to uncontrolled gestational hyperglycemia. Pregnant rats injected with either streptozotocin or vehicle were killed on gestational day 19. Offspring brains were quickly removed to evaluate protein expression by Western blotting. Embryonic brains from diabetic rats exhibited a decrease in the cell survival p-Akt expression (52.83 ± 24.35%) and in the pro-apoptotic protein Bax (56.16 ± 6.47%). Moreover, the anti-apoptotic protein Bcl-2 showed a non-significant increase while there were no changes in Procaspase 3 or cleaved Caspase 3 proteins. The cytoskeleton proteins NF-200 and GFAP were also examined. Neither NF-200 nor GFAP showed differences in embryonic brains from diabetic rats compared to controls. Altogether, these results indicate that both proliferation and apoptotic pathways are decreased in the brain from the developing offspring of diabetic rats. Since selective neuronal apoptosis, as well as selective cell proliferation, are specifically involved in brain organogenesis, it is possible that simultaneous impairments during the perinatal period contribute to the long lasting alterations observed in the adult brain. Content Type Journal Article Category Original Research Pages 1-7 DOI 10.1007/s10571-012-9820-8 Authors María Sol Kruse, Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, Argentina Joaquín Barutta, Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, Argentina María Cristina Vega, Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, Argentina Héctor Coirini, Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, Argentina Journal Cellular and Molecular Neurobiology Online ISSN 1573-6830 Print ISSN 0272-4340