An Unexpected Complication Resulting from Radiofrequency Ablation for Treating Facet Joint Syndrome: A Case Report.

Lumbar facet joints have been identified as a potential source of chronic low back pain (LBP) in 15% to 45% of patients, with the prevalence of such pain varying based on specific populations and settings examined. Lumbar facet joint interventions are useful in the diagnosis as well as the therapeutic management of chronic LBP. Radiofrequency ablation (RFA) of medial branch nerves is recognized as a safe and effective therapy for chronic facet joint pain in the lumbosacral spine, and its efficacy has already been established. The use of RFA is currently widespread in the management of spinal pain, but it is noteworthy that there have been works in the literature reporting complications, albeit at a very low frequency. We present a case of third-degree skin burns following radiofrequency ablation (RFA) for the management of facet joint syndrome. Postoperatively, the patient's skin encircling the needle displayed a pallor and exhibited deterioration in conjunction with the anatomical anomaly. The affected area required approximately 5 months to heal completely. During RFA, heat can induce burns not only at the point of contact with the RF electrode but also along the length of the needle. Vigilant attention is necessary to ensure patient safety and to address any potential complications that may arise during the procedure, including the possibility of minor technical errors.

Distribution patterns of the cutaneous nerves on the dorsum of the foot and their clinical significance.

The aim of this study was to clarify the distribution patterns of the cutaneous nerves on the dorsum of the foot. This study investigated 130 feet of 77 cadavers. The distribution patterns of the sural (SN) and deep fibular nerves (DFN) were classified into five and four types, respectively. In Type A, the SN was only distributed to the lateral side of the fifth toe. In Type B, the nerve was distributed to the medial side of the fourth toe and both sides of the fifth toe. In Type C, the nerve was mainly distributed to the lateral side of the fifth toe. In Type D, the nerve was distributed to the lateral side of the third toe and both sides of the fourth and fifth toes. In Type E, no SN was found. In Type α, the DFN was simultaneously distributed to the lateral side of the first toe and the medial side of the second toe. In Type ß, the nerve was distributed like in Type α and additionally to the medial side of the first toe. In Type γ, the nerve was distributed like in Type α and additionally to the lateral side of the second toe and the medial side of the third toe. In Type δ, no DFN was found. The results of this study will help physicians to reduce the incidence of iatrogenic nerve injury and improve the quality of diagnoses of relevant nerves in this body region. Clin. Anat. 33:592-597, 2020. © 2019 Wiley Periodicals, Inc.

Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation.

Mental health and cognitive functions are influenced by both genetic and environmental factors. Although having active lifestyle with physical exercise improves learning and memory, how it interacts with the specific key molecular regulators of synaptic plasticity is largely unknown. Here, we examined the effects of voluntary running on long-term potentiation (LTP) and memory formation in mice lacking type 1 adenylyl cyclase (AC1), a neurospecific synaptic enzyme that contributes to Ca(2+)-stimulated cAMP production. Following 1 mo of voluntary running-wheel exercise, the impaired LTP and object recognition memory in AC1 knockout (KO) mice were significantly attenuated. Running up-regulated exon II mRNA level of BDNF (brain-derived neurotrophic factor), though it failed to increase exon I and IV mRNAs in the hippocampus of AC1 KO mice. Intrahippocampal infusion of recombinant BDNF was sufficient to rescue LTP and object recognition memory defects in AC1 KO mice. Therefore, voluntary running and exogenous BDNF application overcome the defective Ca(2+)-stimulated cAMP signaling. Our results also demonstrate that alteration in Ca(2+)-stimulated cAMP can affect the molecular outcome of physical exercise.

Experience-Dependent Induction of Hippocampal ΔFosB Controls Learning.

The hippocampus (HPC) is known to play an important role in learning, a process dependent on synaptic plasticity; however, the molecular mechanisms underlying this are poorly understood. ΔFosB is a transcription factor that is induced throughout the brain by chronic exposure to drugs, stress, and variety of other stimuli and regulates synaptic plasticity and behavior in other brain regions, including the nucleus accumbens. We show here that ΔFosB is also induced in HPC CA1 and DG subfields by spatial learning and novel environmental exposure. The goal of the current study was to examine the role of ΔFosB in hippocampal-dependent learning and memory and the structural plasticity of HPC synapses. Using viral-mediated gene transfer to silence ΔFosB transcriptional activity by expressing ΔJunD (a negative modulator of ΔFosB transcriptional function) or to overexpress ΔFosB, we demonstrate that HPC ΔFosB regulates learning and memory. Specifically, ΔJunD expression in HPC impaired learning and memory on a battery of hippocampal-dependent tasks in mice. Similarly, general ΔFosB overexpression also impaired learning. ΔJunD expression in HPC did not affect anxiety or natural reward, but ΔFosB overexpression induced anxiogenic behaviors, suggesting that ΔFosB may mediate attentional gating in addition to learning. Finally, we found that overexpression of ΔFosB increases immature dendritic spines on CA1 pyramidal cells, whereas ΔJunD reduced the number of immature and mature spine types, indicating that ΔFosB may exert its behavioral effects through modulation of HPC synaptic function. Together, these results suggest collectively that ΔFosB plays a significant role in HPC cellular morphology and HPC-dependent learning and memory. SIGNIFICANCE STATEMENT: Consolidation of our explicit memories occurs within the hippocampus, and it is in this brain region that the molecular and cellular processes of learning have been most closely studied. We know that connections between hippocampal neurons are formed, eliminated, enhanced, and weakened during learning, and we know that some stages of this process involve alterations in the transcription of specific genes. However, the specific transcription factors involved in this process are not fully understood. Here, we demonstrate that the transcription factor ΔFosB is induced in the hippocampus by learning, regulates the shape of hippocampal synapses, and is required for memory formation, opening up a host of new possibilities for hippocampal transcriptional regulation.

Possible involvement of hippocampal immediate-early genes in contextual fear memory deficit induced by cranial irradiation.

Cranial irradiation can trigger adverse effects on brain functions, including cognitive ability. However, the cellular and molecular mechanisms underlying radiation-induced cognitive impairments remain still unknown. Immediate-early genes (IEGs) are implicated in neuronal plasticity and the related functions (i.e., memory formation) in the hippocampus. The present study quantitatively assessed changes in the mRNA and protein levels of the learning-induced IEGs, including Arc, c-fos, and zif268, in the mouse hippocampus after cranial irradiation using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. Mice (male, 8-week-old C57BL/6) received whole-brain irradiation with 0 or 10Gy of gamma-ray and, 2weeks later, contextual fear conditioning (CFC) was used to induce IEGs. In the CFC task, mice evaluated 2weeks after irradiation exhibited significant memory deficits compared with sham (0Gy)-irradiated controls. The levels of mRNA encoding IEGs were significantly upregulated in the hippocampus 10 and 30min after CFC training. The mRNA levels in the irradiated hippocampi were significantly lower than those in the sham-irradiated controls. The IEG protein levels were significantly increased in all hippocampal regions, including the hippocampal dentate gyrus, cornu ammonis (CA)1, and CA3, after CFC training. The CFC-induced upregulation of Arc and c-fos in 10Gy-irradiated hippocampi was significantly lower than that in sham-irradiated controls, although there were no significant differences in the protein levels of the learning-induced zif268 between sham-irradiated and 10Gy-irradiated hippocampi. Thus, cranial irradiation with 10Gy of gamma-ray impairs the induction of hippocampal IEGs (particularly Arc and c-fos) via behavioral contextual fear memory, and this disturbance may be associated with the memory deficits evident in mice after cranial irradiation, possibly through the dysregulation of neuronal plasticity during memory formation.

Ethanolic extract of Schizonepeta tenuifolia attenuates osteoclast formation and activation in vitro and protects against lipopolysaccharide-induced bone loss in vivo.

BACKGROUND: Excessive osteoclast activity is a major cause of metabolic bone disorders, such as osteopenia, rheumatoid arthritis, and osteoporosis. Thus, discovery of agents targeting osteoclast differentiation and bone resorption is important for development of novel treatments for bone diseases. It has been demonstrated that ethanolic extract of schizonepeta tenuifolia (EEST) has potent anti-oxidant and anti-inflammatory activities. However, the beneficial effects of EEST on bone metabolism have not been studied. Therefore, we intend to investigate the effects of EEST on osteoclast differentiation. METHODS: We examined the effects and mechanisms of action of the EEST on osteoclastogenesis in vitro in bone marrow macrophages (BMMs) stimulated with receptor activator of nuclear factor kappa-B ligand (RANKL) and in vivo using a mouse model of lipopolysaccharide (LPS)-induced bone destruction. RESULTS: We found that EEST inhibited phosphorylation of Akt and IkB at early stages of RANKL-induced osteoclastogenesis. Furthermore, EEST negatively controlled the transcription and translation levels of nuclear factor of activated T cells c1 (NFATc1) and the translation level of c-Fos at the final stage of osteoclast differentiation. Reflecting these effects, EEST blocked both filamentous actin (F-actin) ring formation and bone resorbing activity of mature osteoclasts in vitro. The inhibitory effects of EEST on osteoclast formation and activity were observed in an LPS-mediated bone erosion mouse model using micro-CT and histological analysis. CONCLUSIONS: EEST is a potential agent that is able to treat osteoclast-related bone diseases, such as osteoporosis.

Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo.

Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects of DM on bone diseases such as osteoporosis. Thus, we investigated the relationship between DM and osteoclasts, cells that function in bone resorption. We found that DM significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation; DM directly induced the down-regulation of c-Fos and nuclear factor of activated T cells c1 (NFATc1) without affecting other RANKL-dependent transduction pathways. In the later stages of osteoclast maturation, DM negatively regulated the organization of filamentous actin (F-actin), resulting in impaired bone-resorbing activity by the mature osteoclasts. In addition, micro-computed tomography (µ-CT) analysis of the murine model revealed that DM had a beneficial effect on lipopolysaccharide (LPS)-mediated bone erosion. Histological analysis showed that DM attenuated the degradation of trabecular bone matrix and formation of TRAP-positive osteoclasts in bone tissues. These results suggest that DM is a potential candidate for the treatment of metabolic bone disorders such as osteoporosis.

Cranial irradiation regulates CREB-BDNF signaling and variant BDNF transcript levels in the mouse hippocampus.

The brain can be exposed to ionizing radiation in various ways, and such irradiation can trigger adverse effects, particularly on learning and memory. However, the precise mechanisms of cognitive impairments induced by cranial irradiation remain unknown. In the hippocampus, brain-derived neurotrophic factor (BDNF) plays roles in neurogenesis, neuronal survival, neuronal differentiation, and synaptic plasticity. The significance of BDNF transcript variants in these contexts is becoming clearer. In the present study, both object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice were assessed 1 month after a single exposure to cranial irradiation (10 Gy) to evaluate hippocampus-related behavioral dysfunction following such irradiation. Furthermore, changes in the levels of BDNF, the cAMP-response element binding protein (CREB) phosphorylation, and BDNF transcript variants were measured in the hippocampus 1 month after cranial irradiation. On object recognition memory and contextual fear conditioning tasks, mice evaluated 1 month after irradiation exhibited significant memory deficits compared to sham-irradiated controls, but no apparent change was evident in locomotor activity. Both phosphorylated CREB and BDNF protein levels were significantly downregulated after irradiation of the hippocampus. Moreover, the levels of mRNAs encoding common BDNF transcripts, and exons IIC, III, IV, VII, VIII, and IXA, were significantly downregulated after irradiation. The reductions in CREB phosphorylation and BDNF expression induced by differential regulation of BDNF hippocampal exon transcripts may be associated with the memory deficits evident in mice after cranial irradiation.

Hippocampal dysfunctions caused by cranial irradiation: a review of the experimental evidence.

Cranial irradiation (IR) is commonly used for the treatment of brain tumors but may cause disastrous brain injury, especially in the hippocampus, which has important cognition and emotional regulation functions. Several preclinical studies have investigated the mechanisms associated with cranial IR-induced hippocampal dysfunction such as memory defects and depression-like behavior. However, current research on hippocampal dysfunction and its associated mechanisms, with the ultimate goal of overcoming the side effects of cranial radiation therapy in the hippocampus, is still very much in progress. This article reviews several in vivo studies on the possible mechanisms of radiation-induced hippocampal dysfunction, which may be associated with hippocampal neurogenesis, neurotrophin and neuroinflammation. Thus, this review may be helpful to gain new mechanistic insights into hippocampal dysfunction following cranial IR and provide effective strategies for potential therapeutic approaches for cancer patients receiving radiation therapy.

Hippocampal dysfunctions in tumor-bearing mice.

Individuals with cancer are particularly susceptible to depression and cognitive impairment. However, the precise mechanisms underlying cancer-induced hippocampal dysfunction are poorly understood. We investigated the effects of a peripheral tumor on emotional behavior, hippocampus-dependent memory and associated molecular and cellular features using an experimental animal model. Behavioral alterations were examined; stress-related parameters measured; hippocampal neurogenesis evaluated; and the levels of pro-inflammatory cytokines, brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2) assayed, 2 weeks after inoculation of adult BALB/c mice with cells of a colon carcinoma cell line (CT26). As the tumors developed, CT26-inoculated mice showed significant increases in the depression-like behavior (measured using the tail suspension test) and memory impairment (in terms of object recognition) compared with vehicle-inoculated controls. The presence of a peripheral tumor significantly elevated the hippocampal levels of mRNAs encoding interleukin-6 (IL-6) and tumor necrosis factor-α, as well as plasma IL-6 and corticosterone levels. Additionally, the adrenal glands became enlarged, and the numbers of Ki-67-positive proliferating hippocampal cells and doublecortin-positive immature progenitor neurons, as well as the constitutive levels of mRNAs encoding BDNF and COX-2 were significantly reduced. Therefore, a peripheral tumor alone may be sufficient to induce hippocampal dysfunction, possibly by reducing the rate of neurogenesis and the levels of BDNF and COX-2 in that tissue and also by increasing stress-related parameters and the circulating levels of pro-inflammatory cytokines.

Comparison of international medical costs for interventional pain treatment: a focus on Korea and Japan.

Background: The rise in national health care costs has emerged as a global problem given the ever-aging population and rapid development of medical technology. The utilization of interventional pain management has, similarly, shown a continued rise worldwide. This study evaluates the differences in the medical costs in the field of interventional pain treatment (IPT) between two countries: Korea and Japan. Methods: Korean medical insurance costs for 2019 related to pain management focused on IPT were compared to those of Japan. Purchasing power parity (PPP) was used to adjust the exchange rate differences and to compare prices in consideration of the respective societies' economic power. Results: The cost of trigger point injections in Japan was 1.06 times higher than that of Korea, whereas the perineural and intraarticular injection prices were lower in Japan. The cost of epidural blocks was higher in Japan compared to Korea in both cervical/thoracic and lumbar regions. As for blocks of peripheral branches of spinal nerves, the cost of scapular nerve blocks in Japan was lower than that in Korea, given a PPP ratio 0.09. For nerve blocks in which fluoroscopy guidance is mandatory, the costs of epidurography in Japan were greater than those in Korea, given a PPP ratio 1.04. Conclusions: This is the first comparative study focusing on the medical costs related to IPT between Korea and Japan, which reveals that the costs differed along various categories. Further comparisons reflecting more diverse countries and socio-economic aspects will be required.

New insight into the vasto-adductor membrane for safer adductor canal blockade.

Background: : This study aimed to identify exact anatomical landmarks and ideal injection volumes for safe adductor canal blocks (ACB). Methods: : Fifty thighs from 25 embalmed adult Korean cadavers were used. The measurement baseline was the line connecting the anterior superior iliac spine (ASIS) to the midpoint of the patellar base. All target points were measured perpendicular to the baseline. The relevant cadaveric structures were observed using ultrasound (US) and confirmed in living individuals. US-guided dye injection was performed to determine the ideal volume. Results: : The apex of the femoral triangle was 25.3 ± 2.2 cm distal to the ASIS on the baseline and 5.3 ± 1.0 cm perpendicular to that point. The midpoint of the superior border of the vasto-adductor membrane (VAM) was 27.4 ± 2.0 cm distal to the ASIS on the baseline and 5.0 ± 1.1 cm perpendicular to that point. The VAM had a trapezoidal shape and was connected as an aponeurosis between the medial edge of the vastus medialis muscle and lateral edge of the adductor magnus muscle. The nerve to the vastus medialis penetrated the muscle proximal to the superior border of the VAM in 70% of specimens. The VAM appeared on US as a hyperechoic area connecting the vastus medialis and adductor magnus muscles between the sartorius muscle and femoral artery. Conclusions: : Confirming the crucial landmark, the VAM, is beneficial when performing ACB. It is advisable to insert the needle obliquely below the superior VAM border, and a 5 mL injection is considered sufficient.

Coccydynia: anatomic origin and considerations regarding the effectiveness of injections for pain management.

Coccydynia is a debilitating pain disorder. However, its pathophysiology is not well understood. When approaching coccydynia, the exact underlying cause of pain must be identified to develop an appropriate treatment plan. The specific approach to coccydynia can vary depending on an individual's condition and the underlying cause. Thorough evaluation by a pain physician is essential to determine the most appropriate course of treatment. The purpose of this review is to examine the various causes contributing to coccygeal pain and specifically focus on the exact anatomical neurostructures, such as the anococcygeal nerve, perforating cutaneous nerve, and ganglion impar. We also reviewed the relevant clinical outcomes and suggested recommendations for each anatomical structure.

The current status of fibromyalgia in Korea: an electronic population health data study in Korea.

Background: Fibromyalgia (FM) is a complex disorder characterized by widespread chronic pain and tenderness in the muscles, ligaments, and soft tissues. It is a chronic pain condition often accompanied by other symptoms and comorbidities. To effectively manage FM, it is crucial to obtain fundamental epidemiological data pertaining to the target population. Therefore, this study was conducted to elucidate the epidemiological characteristics of FM in the Korean population. Methods: Population-based medical data of 51,276,314 subscribers to the National Health Insurance Service of Korea from 2014 to 2018 were used in this study. Results: The overall incidence of FM ranged from 441 (2014) to 541 (2018) cases per 100,000 person-years, with a higher prevalence observed among female patients compared to male patients. The incidence gradually increased until middle age, followed by a decrease. The highest incidence rates were observed in the fifth decade of life for females and the sixth decade of life for males. When categorizing the affected parts of the body, the shoulder region was observed to be the most frequently affected. A comparison of the drug prescriptions based on medical specialty showed that antidepressants were the most commonly prescribed medications. The management of FM leads to consistent increases in medical expenses, regional disparities, and variations in prescription patterns across different medical specialties. Conclusions: The findings of this study will not only contribute to the understanding of FM characteristics but also provide a vital foundation for efficient management of FM in Korea.

New insight into the mandibular nerve at the foramen ovale level for percutaneous radiofrequency thermocoagulation.

Background: Percutaneous radiofrequency thermocoagulation (RFTC) has been widely utilized in the management of trigeminal neuralgia. Despite using image guidance, accurate needle positioning into the target area still remains a critical element for achieving a successful outcome. This study was performed to precisely clarify the anatomical information required to ensure that the electrode tip is placed on the sensory component of the mandibular nerve (MN) at the foramen ovale (FO) level. Methods: The study used 50 hemi-half heads from 26 South Korean adult cadavers. Results: The cross-sectioned anterior and posterior divisions of the MN at the FO level could be distinguished based on an irregular boundary and color difference. The anterior division was clearly brighter than the posterior one. The anterior division of the MN at the FO level was located at the whole anterior (38.0%), anteromedial (6.0%), anterior center (8.0%), and anterolateral (22.0%) parts. The posterior division was often located at the whole posterior or posterolateral parts of the MN at the FO level. The anterior divisions covered the whole MN except for the medial half of the posterolateral part in the overwrapped images of the cross-sectional areas of the MN at the FO level. The cross-sectional areas of the anterior divisions were similar in males and females, whereas those of the posterior divisions were significantly larger in males (P = 0.004). Conclusions: The obtained anatomical information is expected to help physicians reduce unwanted side effects after percutaneous RFTC within the FO for the MN.

Effects of Gestational and Lactational Lead Exposure and High Fat Diet Feeding on Cerebellar Development of Postnatal Rat Offspring.

Obesity and heavy metals, such as lead (Pb), are detrimental to the adult brain because they impair cognitive function and structural plasticity. However, the effects of co-administration of Pb and a high-fat diet (HFD) on the developing cerebellum is not clearly elucidated. We investigated the effects of Pb exposure (0.3% lead acetate) on developing cerebellum in the pups of an HFD-fed obese rat model. One week before mating, we fed a chow diet (CD) or HFD to the rats for one week and additionally administered Pb to HFD-fed female SD rats. Thereafter, treatment with Pb and a HFD was continued during the gestational and lactational periods. On postnatal day 21, the pups were euthanized to sample the brain tissue and blood for further analysis. Blood Pb levels were significantly higher in HFD-fed rats than in CD-fed rats. Histologically, the prominent degeneration of Purkinje cells was induced by the co-administration of Pb and HFD. The calbindin-28Kd-, GAD67-, NMDAR1-, and PSD95-immunopositive Purkinje cells and inhibitory synapse-forming pinceau structures were significantly decreased following Pb and HFD co-administration. MBP-immunoreactive myelinated axonal fibers were also impaired by HFD but were significantly damaged by the co-administration of HFD and Pb. Oxidative stress-related Nrf2-HO1 signaling was activated by HFD feeding, and Pb exposure further aggravated oxidative stress, as demonstrated by the consumption of endogenous anti-oxidant in HFD-Pb rats. The pro-inflammatory response was also increased by the co-administration of HFD and Pb in the cerebellum of the rat offspring. The present results suggest that HFD and Pb treatment during the gestational and lactational periods are harmful to cerebellar development.

Evaluation of the antiosteoporotic potential of Cimicifuga heracleifolia in female mice.

Cimicifugae rhizoma might be protective against osteoporosis. This study investigated the effects of Cimicifuga heracleifolia (CH), an Asian species of Cimicifugae rhizome, on bone loss in ovariectomized (OVX) mice. The C3H/HeN mice were divided into sham and OVX groups. The OVX mice were treated with vehicle, 17ß-estradiol (E(2) ) or CH for 6 weeks. Serum calcium, phosphorus, E(2) concentration and serum alkaline phosphatase (ALP) activity were measured. Tibiae and femora were analysed using microcomputed tomography. The biomechanical property and osteoclast surface level were measured. Treatment with CH (i.p., 50 mg/kg of body weight, every other day) prevented the OVX-induced increase in body weight but did not alter the uterus weight of the OVX mice. Serum ALP levels and osteoclast surface levels in the OVX mice were reduced by treatment with CH. The CH significantly preserved trabecular bone mass, bone volume, trabecular number, trabecular thickness, structure model index and bone mineral density of proximal tibia metaphysis or distal femur metaphysis. However, grip strength, mechanical property and cortical bone architecture did not differ among the experimental groups. The results indicate that the supply of CH can prevent OVX-induced bone loss in mice.

Acute MPTP Treatment Impairs Dendritic Spine Density in the Mouse Hippocampus.

Among the animal models of Parkinson's disease (PD), the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model has shown both dopaminergic (DA) damage and related motor control defects, as observed in patients with PD. Recent studies have suggested that the DA system interacts with the synaptic plasticity of the hippocampus in PD. However, little is known about how alterations in the hippocampal structural plasticity are affected by the DA damage in MPTP-lesioned models. In the present study, we investigated alterations in dendritic complexity and spine density in the mouse hippocampus following acute MPTP treatment (22 mg/kg, intraperitoneally, four times/day, 2-h intervals). We confirmed that acute MPTP treatment significantly decreased initial motor function and persistently reduced the number of tyrosine hydroxylase-positive DA neurons in the substantia nigra. Golgi staining showed that acute MPTP treatment significantly reduced the spine density of neuronal dendrites in the cornu ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions of the mouse hippocampus at 8 and 16 days after treatment, although it did not affect dendritic complexity (e.g., number of crossing dendrites, total dendritic length, and branch points per neuron) in both CA1 and DG subregions at all time points after treatment. Therefore, the present study provides anatomical evidence that acute MPTP treatment affects synaptic structure in the hippocampus during the late phase after acute MPTP treatment in mice, independent of any changes in the dendritic arborization of hippocampal neurons. These findings offer data for the ability of the acute MPTP-lesioned mouse model to replicate the non-nigrostriatal lesions of clinical PD.

Cyclophosphamide impairs hippocampus-dependent learning and memory in adult mice: Possible involvement of hippocampal neurogenesis in chemotherapy-induced memory deficits.

Cyclophosphamide (CYP) is an anti-neoplastic agent as well as an immunosuppressive agent. In order to elucidate the alteration in adult hippocampal function following acute CYP treatment, hippocampus-related behavioral dysfunction and changes in adult hippocampal neurogenesis in CYP-treated (intraperitoneally, 40 mg/kg) mice (8-10-week-old ICR) were analyzed using hippocampus-dependent learning and memory tasks (passive avoidance and object recognition memory test) and immunohistochemical markers of neurogenesis (Ki-67 and doublecortin (DCX)). Compared to the vehicle-treated controls, mice trained at 12h after CYP injection showed significant memory deficits in passive avoidance and the object recognition memory test. The number of Ki-67- and DCX-positive cells began to decrease significantly at 12h post-injection, reaching the lowest level at 24h after CYP injection; however, this reverted gradually to the vehicle-treated control level between 2 and 10 days. We suggest that the administration of a chemotherapeutic agent in adult mice interrupts hippocampal functions, including learning and memory, possibly through the suppression of hippocampal neurogenesis.

Gamma-ray susceptibility of immature and mature hippocampal cultured cells.

Ionizing radiation suppresses neurogenesis in the mammalian brain. This in vitro study compared the detrimental effect of acute gamma-irradiation on immature hippocampal cells with mature cells. Both rat immature (0.5 day in vitro (DIV)) and mature hippocampal cells (14 DIV) were irradiated with 0-4 Gy gamma-rays. Cell viability was analyzed by using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. DNA fragmentation study was performed by extracting intracellular DNA. Morphological features of apoptosis were characterized by 4',6-diamidine-2'-phenylindole, dihydrochloride (DAPI) staining. MTT assay revealed that the survival rate of immature hippocampal cells declined in a dose-dependent manner within the range of irradiation applied, but was not changed in mature cells. Intranucleosomal DNA fragmentation in a ladder like pattern was dose-dependently increased in immature cells, but not in mature cells. The number of apoptotic nuclei in immature cells increased significantly in a dose-dependent manner within the range of irradiation applied. Active caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) expressions in immature hippocampal cells at 6 hr after 2 Gy exposure were markedly higher than control levels. The significantly greater radiosensitivity of immature hippocampal cells than that of the mature cells, indicates that the susceptibility of such hippocampal cells depends on their maturation. In addition, gamma-irradiation may induce caspase-dependent apoptosis in immature hippocampal cells.