Neurodevelopmental Disorder Traits in Taijin-Kyofu-sho and Social Anxiety Disorder: A Cross-Sectional Study among University Students.

Taijin-Kyofu-sho is an East Asian culture-bound anxiety disorder with similarities to social anxiety disorder. However, few studies have examined these two disorders from the perspective of neurodevelopmental disorders. This study is aimed at examining the association of Taijin-Kyofu-sho and social anxiety disorder with the attention-deficit/hyperactivity disorder (ADHD) trait and autism spectrum disorder (ASD) trait. The Liebowitz Social Anxiety, Taijin-Kyofu-sho, and Adult Attention-Deficit/Hyperactivity Disorder Self-Report scales and the 16-item Autism-Spectrum Quotient were administered to 818 university students. Participants were divided into four groups: control (neither Taijin-Kyofu-sho nor social anxiety disorder), pure Taijin-Kyofu-sho (Taijin-Kyofu-sho alone), pure social anxiety disorder (social anxiety disorder alone), and mixed Taijin-Kyofu-sho-social anxiety disorder (both Taijin-Kyofu-sho and social anxiety disorder). We used logistic regression analysis to examine whether the ADHD trait and ASD trait were associated with Taijin-Kyofu-sho and social anxiety disorder. ASD trait was significantly associated with pure Taijin-Kyofu-sho (p = 0.006, odds ratio: 3.99). Female sex and ADHD trait were significantly associated with pure social anxiety disorder (sex: p = 0.013, odds ratio: 2.61; ADHD trait: p = 0.012, odds ratio: 2.46). Female sex, ADHD trait, and ASD trait were significantly associated with mixed Taijin-Kyofu-sho-social anxiety disorder (sex: p = 0.043, odds ratio: 2.16; ADHD trait: p = 0.003, odds ratio: 2.75; ASD trait: p < 0.001, odds ratio: 16.93). Neurodevelopmental disorder traits differed between individuals with Taijin-Kyofu-sho and those with social anxiety disorder. Overall, our study reveals that Japanese individuals with the ADHD or ASD traits are at a heightened risk of developing Taijin-Kyofu-sho or social anxiety disorder.

Short-term effect of a smartphone application on the mental health of university students: A pilot study using a user-centered design self-monitoring application for mental health.

BACKGROUND: Despite the widespread recognition of the importance of mental health in young people, only a small proportion of young people with a mental disorder, including university students, receive mental health care. OBJECTIVE: We developed a smartphone application (Mental App) for the university students and examined the effects of the app on their mental health. METHODS: The app was designed according to a questionnaire survey conducted before this study. The Mental App was installed on the students' smartphone and the psychological tests (the Link Stigma Scale, the Center for Epidemiologic Studies Depression Scale, and the 12-item General Health Questionnaire) were performed on the same day. After using the App for two weeks, the students completed a questionnaire survey and underwent the same psychological tests. We compared the results between the app user and non-user group. RESULTS: A total of 68 students participated, of which 57 students completed the study (app user group, n = 28; control group, n = 29). The mean number of days spent using the app was 5.66 ± 3.16 (mean ± SD). The mean total screen time of the app was 9:03 ± 06:41(min:sec). The mean number of total actions (screen taps or swipes) was 161.91 ± 107.34. There were no significant between-group differences in the ΔLink Stigma Scale score (-0.11 ± 4.28 vs. -0.59 ± 3.30, p = 0.496) or the ΔCenter for Epidemiologic Studies Depression Scale score (-4.39 ± 7.13 vs. -2.07 ± 8.78, p = 0.143). There was a significant between-group difference in the ΔGeneral Health Questionnaire score (-2.21± 2.23 vs. -0.17 ± 2.69, p = 0.007). CONCLUSIONS: This non-randomized controlled pilot study indicates that the app we developed, may provide effective mental health care for university students, even in the short-term. Trial registration: UMIN000040332.

Contributions of Anthropometrics and Lifestyle to Blood Pressure in Japanese University Students†:†Investigation by Annual Health Screening.

Background : High blood pressure (BP) is a healthcare problem in young persons. There are racial differences in anthropometrics, dietary habit and lifestyle relating to BP. Therefore, this study investigated the relationship between anthropometrics, lifestyle and BP obtained in the Japanese university students. Materials and Methods : Participants were recruited in annual health screening including questionnaire, measurements of BP and anthropometrics calculating body mass index (BMI). Totally, 14,280 students (10,273 males and 4,007 females) were eligible. Multiple regression analyses were applied to predict contributors to high BP. Results : BMI was the most powerful contributor to high BP in many subgroups divided by gender and graduation (p < 0.001). In lifestyle, contribution of lack of exercise to high BPs was observed in the undergraduates. Smoking, drinking and breakfast skipping had no significant impact on high BP. However, smoking and drinking permeated and exercise habit declined after graduation. Prevalence of obesity (BMI ≥ 25 kg / m2) and hypertension ( ≥ 140 / 90 mmHg) increased in subgroups with advanced age (p < 0.001). Conclusion: BMI was found to be the most powerful contributor to high BPs. Health literacy to modify lifestyle is important to prevent hypertension for university students who are exposed to social trends of unhealthy lifestyle. J. Med. Invest. 67 : 174-181, February, 2020.

Relevance of hoarding behavior and the traits of developmental disorders among university students: a self-reported assessment study.

BACKGROUND: Previous studies have shown that hoarding behavior usually starts at a subclinical level in early adolescence and gradually worsens; however, a limited number of studies have examined the prevalence of hoarding behavior and its association with developmental disorders in young adults. The aims of this study were to estimate the prevalence of hoarding behavior and to identify correlations between hoarding behavior and developmental disorder traits in university students. METHODS: The study participants included 801 university students (616 men, 185 women) who completed questionnaires (ASRS: Adult ADHD Self-Report Scale version 1.1, AQ16: Autism-Spectrum Quotient with 16 items, and CIR: Clutter Image Rating). RESULTS: Among 801 participants, 27 (3.4%) exceeded the CIR cut-off score. Moreover, the participants with hoarding behavior had a significantly higher percentage of ADHD traits compared to participants without hoarding behavior (HB(+) vs HB(-), 40.7% vs 21.7%). In addition, 7.4% of HB(+) participants had autism spectrum disorder (ASD) traits, compared to 4.1% of HB(-) participants. A correlation analysis revealed that the CIR composite score had a stronger correlation with the ASRS inattentive score than with the hyperactivity/impulsivity score (CIR composite vs ASRS IA, r = 0.283; CIR composite vs ASRS H/I, r = 0.147). CONCLUSIONS: The results showed a high prevalence of ADHD traits in the university students with hoarding behavior. Moreover, we found that the hoarding behavior was more strongly correlated with inattentive symptoms rather than with hyperactivity/impulsivity symptoms. Our results support the concept of a common pathophysiology behind hoarding behavior and ADHD in young adults.

Correlation between Taijin-Kyofu-sho and Attention Deficit Hyperactivity Disorder among University Students: A Self-Reported Assessment Study.

Taijin-Kyofu-sho (TK) is regarded as a culture-bound anxiety disorder in East Asian counties. Despite its earlier discovery in Japan, fewer studies have focused on TK than on social anxiety disorder (SAD) and even fewer on TK comorbidity with developmental disorders. Thus, we examined the association between TK and attention deficit hyperactivity disorder (ADHD) among Japanese university students. A total of 673 students (500 male, 173 female) were assessed on the Japanese version of Liebowitz Social Anxiety Scale (LSAS-J), TK scale, and adult ADHD Self-Report Scale (ASRS; version 1.1). On the TK scale and LSAS-J, 17.4 and 10.3 percent of students, respectively, exceeded the cut-off value. Furthermore, ASRS scores more strongly correlated with TK scale than LSAS-J scores (TK scale: r = 0.427; LSAS-J: r = 0.330). To evaluate how TK or SAD with ADHD affects those scores, we divided subjects into four groups: healthy subjects, subjects with TK, those with SAD, and those with both disorders. The total ASRS score was significantly higher in TK-only subjects than in healthy subjects (p < 0.0001). However, there was no significant difference between scores of healthy and SAD-only subjects (p = 0.281). Our results indicate a possible link between ADHD and later development of TK in Japan.

Chronic atypical antipsychotics, but not haloperidol, increase neurogenesis in the hippocampus of adult mouse.

It is suggested that altered neuroplasticity contributes to the pathophysiology of schizophrenia and antipsychotics may exhibit some of their therapeutic efficacies by improving neurogenesis and/or proliferation of neural progenitors. The aim of this study is to investigate whether chronic antipsychotics treatment affect neurogenesis in adult mouse hippocampus. Animals were administered olanzapine, quetiapine, clozapine, risperidone, aripiprazole, or haloperidol via the osmotic minipump for 21days and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. BrdU-positive cells in the hippocampus were quantified by stereology. Aripiprazole, quetiapine, clozapine, and olanzapine significantly increased density of BrdU-positive cells in the hippocampus. Interestingly, other antipsychotic drugs had tendency to increasing BrdU-positive cells, whereas haloperidol had propensity to decrease with a marginal significance. These results suggest that differences of neurogenesis among these drugs may, at least in part, account for their pharmacological profiles.

Serum galectin-3, but not galectin-1, levels are elevated in schizophrenia: implications for the role of inflammation.

BACKGROUND: Previous studies have reported that galectin-3 is involved in inflammatory processes in the central nervous system and that neuroinflammation may play a role in the pathogenesis of schizophrenia. However, the link between schizophrenia and various galectins is unclear. OBJECTIVE: The objective of the present study is to determine whether galectin, a well-known lectin protein that binds to µ-galactoside, is associated with chronic schizophrenia. METHODS: Thirty-six patients with schizophrenia and 36 healthy controls participated in this study. Schizophrenia symptoms were assessed using the Brief Psychiatry Rating Scale (BPRS). Serum galectin-1 and galectin-3 levels were evaluated using ELISA and compared between the participant groups. Correlation analyses were also performed to examine the relationship between BPRS scores and each galectin level. RESULTS: Serum galectin-3 levels were significantly higher in patients with schizophrenia than they were in controls (p = 0.009, d = 0.640); however, serum galectin-1 levels were not significantly different between the groups (p = 0.513). No significant correlation was identified between serum galectin-3 level and the total BPRS score; however, a significant positive correlation was found between the serum galectin-3 level and the positive symptom score of the BPRS (ρ = 0.355; p = 0.033). Additionally, a significant negative correlation was identified between serum galectin-3 levels and the negative symptom score of the BPRS (ρ = -0.387; p = 0.020). CONCLUSIONS: Given the high serum levels of galectin-3 found in patients with schizophrenia compared with that in controls, these findings may support the inflammation hypothesis of schizophrenia.

PKCη deficiency improves lipid metabolism and atherosclerosis in apolipoprotein E-deficient mice.

Genomewide association studies have shown that a nonsynonymous single nucleotide polymorphism in PRKCH is associated with cerebral infarction and atherosclerosis-related complications. We examined the role of PKCη in lipid metabolism and atherosclerosis using apolipoprotein E-deficient (Apoe-/- ) mice. PKCη expression was augmented in the aortas of mice with atherosclerosis and exclusively detected in MOMA2-positive macrophages within atherosclerotic lesions. Prkch+/+ Apoe-/- and Prkch-/- Apoe-/- mice were fed a high-fat diet (HFD), and the dyslipidemia observed in Prkch+/+ Apoe-/- mice was improved in Prkch-/- Apoe-/- mice, with a particular reduction in serum LDL cholesterol and phospholipids. Liver steatosis, which developed in Prkch+/+ Apoe-/- mice, was improved in Prkch-/- Apoe-/- mice, but glucose tolerance, adipose tissue and body weight, and blood pressure were unchanged. Consistent with improvements in LDL cholesterol, atherosclerotic lesions were decreased in HFD-fed Prkch-/- Apoe-/- mice. Immunoreactivity against 3-nitrotyrosine in atherosclerotic lesions was dramatically decreased in Prkch-/- Apoe-/- mice, accompanied by decreased necrosis and apoptosis in the lesions. ARG2 mRNA and protein levels were significantly increased in Prkch-/- Apoe-/- macrophages. These data show that PKCη deficiency improves dyslipidemia and reduces susceptibility to atherosclerosis in Apoe-/- mice, showing that PKCη plays a role in atherosclerosis development.

Galectin-1 deficiency improves axonal swelling of motor neurones in SOD1(G93A) transgenic mice.

AIMS: Galectin-1, a member of the ß-galactoside-binding lectin family, accumulates in neurofilamentous lesions in the spinal cords of both sporadic and familial amyotrophic lateral sclerosis (ALS) patients with a superoxide dismutase 1 gene (SOD1) mutation (A4V). The aim of this study was to evaluate the roles of endogenous galectin-1 in the pathogenesis of ALS. METHODS: Expression of galectin-1 in the spinal cord of mutant SOD1 transgenic (SOD1(G93A) ) mice was examined by pathological analysis, real-time RT-PCR and Western blotting. The effects of galectin-1 deficiency were evaluated by cross-breeding SOD1(G93A) mice with galectin-1 null (Lgals1(-/-) ) mice. RESULTS: Before ALS-like symptoms developed in SOD1(G93A) /Lgals1(+/+) mice, strong galectin-1 immunoreactivity was observed in swollen motor axons and colocalized with aggregated neurofilaments. Electron microscopic observations revealed that the diameters of swollen motor axons in the spinal cord were significantly smaller in SOD1(G93A) /Lgals1(-/-) mice, and there was less accumulation of vacuoles compared with SOD1(G93A) /Lgals1(+/+) mice. In symptomatic SOD1(G93A) /Lgals1(+/+) mice, astrocytes surrounding motor axons expressed a high level of galectin-1. CONCLUSIONS: Galectin-1 accumulates in neurofilamentous lesions in SOD1(G93A) mice, as previously reported in humans with ALS. Galectin-1 accumulation in motor axons occurs before the development of ALS-like symptoms and is associated with early processes of axonal degeneration in SOD1(G93A) mice. In contrast, galectin-1 expressed in astrocytes may be involved in axonal degeneration during symptom presentation.

Fosb gene products contribute to excitotoxic microglial activation by regulating the expression of complement C5a receptors in microglia.

The Fosb gene encodes subunits of the activator protein-1 transcription factor complex. Two mature mRNAs, Fosb and ΔFosb, encoding full-length FOSB and ΔFOSB proteins respectively, are formed by alternative splicing of Fosb mRNA. Fosb products are expressed in several brain regions. Moreover, Fosb-null mice exhibit depressive-like behaviors and adult-onset spontaneous epilepsy, demonstrating important roles in neurological and psychiatric disorders. Study of Fosb products has focused almost exclusively on neurons; their function in glial cells remains to be explored. In this study, we found that microglia express equivalent levels of Fosb and ΔFosb mRNAs to hippocampal neurons and, using microarray analysis, we identified six microglial genes whose expression is dependent on Fosb products. Of these genes, we focused on C5ar1 and C5ar2, which encode receptors for complement C5a. In isolated Fosb-null microglia, chemotactic responsiveness toward the truncated form of C5a was significantly lower than that in wild-type cells. Fosb-null mice were significantly resistant to kainate-induced seizures compared with wild-type mice. C5ar1 mRNA levels and C5aR1 immunoreactivity were increased in wild-type hippocampus 24 hours after kainate administration; however, such induction was significantly reduced in Fosb-null hippocampus. Furthermore, microglial activation after kainate administration was significantly diminished in Fosb-null hippocampus, as shown by significant reductions in CD68 immunoreactivity, morphological change and reduced levels of Il6 and Tnf mRNAs, although no change in the number of Iba-1-positive cells was observed. These findings demonstrate that, under excitotoxicity, Fosb products contribute to a neuroinflammatory response in the hippocampus through regulation of microglial C5ar1 and C5ar2 expression.

Characterization of galectin-1-positive cells in the mouse hippocampus.

Galectin-1 (gal-1) is one of several well-studied proteins from the galectin families. It is a 14.5 kDa glycoprotein with a single carbohydrate-binding domain. To examine the distribution and properties of gal-1 in the mouse hippocampus, we performed immunohistochemistry using an anti-gal-1 antibody. We found that most gal-1-positive cells showed both NeuN and ß-tubulin III (Tuj-1) immunoreactivity (NeuN: 93%, ß-tubulin III: 88%). Furthermore, we clarified that 77% of gal-1-positive cells expressed somatostatin, 79% of gal-1-positive cells expressed GAD67, 34% of gal-1-positive cells expressed parvalbumin, 5% of gal-1-positive cells expressed calretinin, 2% of gal-1-positive cells expressed calbindin, and 31% of gal-1-positive cells expressed neuropeptide Y in the mouse hippocampus. These results indicate that gal-1 is expressed in interneurons that also express ß-tubulin III and gal-1 may be a novel marker for interneuron subpopulations in the hippocampus.

fosB-null mice display impaired adult hippocampal neurogenesis and spontaneous epilepsy with depressive behavior.

Patients with epilepsy are at high risk for major depression relative to the general population, and both disorders are associated with changes in adult hippocampal neurogenesis, although the mechanisms underlying disease onset remain unknown. The expression of fosB, an immediate early gene encoding FosB and ΔFosB/Δ2ΔFosB by alternative splicing and translation initiation, is known to be induced in neural progenitor cells within the subventricular zone of the lateral ventricles and subgranular zone of the hippocampus, following transient forebrain ischemia in the rat brain. Moreover, adenovirus-mediated expression of fosB gene products can promote neural stem cell proliferation. We recently found that fosB-null mice show increased depressive behavior, suggesting impaired neurogenesis in fosB-null mice. In the current study, we analyzed neurogenesis in the hippocampal dentate gyrus of fosB-null and fosB(d/d) mice that express ΔFosB/Δ2ΔFosB but not FosB, in comparison with wild-type mice, alongside neuropathology, behaviors, and gene expression profiles. fosB-null but not fosB(d/d) mice displayed impaired neurogenesis in the adult hippocampus and spontaneous epilepsy. Microarray analysis revealed that genes related to neurogenesis, depression, and epilepsy were altered in the hippocampus of fosB-null mice. Thus, we conclude that the fosB-null mouse is the first animal model to provide a genetic and molecular basis for the comorbidity between depression and epilepsy with abnormal neurogenesis, all of which are caused by loss of a single gene, fosB.

Developmental expression of the cyclin D2 splice variant in postnatal Purkinje cells of the mouse cerebellum.

In the present study, we compared the expression of cyclin D2 and D2SV, the cyclin D2 splice variant, in mouse cerebellum at postnatal day 1 (P1), P7, P14 and P28. Western blotting revealed that cyclin D2 levels (34kDa) peaked at P7 and then decreased to levels near the limit of detection at P28. To detect D2SV, we generated a rabbit polyclonal antibody directed against a C-terminal motif unique to this protein that recognizes two D2SV immunoreactive bands at 20 and 25kDa. Western blotting indicated that levels of the 20kDa band remained constant from P1 to P28 while the intensity of the 25kDa band decreased gradually over this period of time. At P7, cyclin D2 immunoreactivity was evident throughout the cerebellum where it was located in nestin-positive cells. By contrast, at P28, cyclin D2 immunoreactivity was restricted to Bergmann glia whose cell bodies are located in the Purkinje cell layer and processes extend into the molecular layer. Unlike cyclin D2, D2SV immunoreactivity was restricted to Purkinje cells at both P7 and P28. Our observations that D2SV immunoreactivity is localized to Purkinje cells and reflects changing levels of at least two D2SV immunoreactive proteins suggests that this splice variant may play an important role in the postnatal development of these neurons.

Nitric oxide synthase mediates the ability of darbepoetin alpha to improve the cognitive performance of STOP null mice.

STOP (stable tubule only polypeptide) null mice display neurochemical and behavioral abnormalities that resemble several well-recognized features of schizophrenia. Recent evidence suggests that the hematopoietic growth factor erythropoietin improves the cognitive performance of schizophrenics. The mechanism, however, by which erythropoietin is able to improve the cognition of schizophrenics is unclear. To address this question, we first determined whether acute administration of the erythropoietin analog known as darbepoetin alpha (D. alpha) improved performance deficits of STOP null mice in the novel objective recognition task (NORT). NORT performance of STOP null mice, but not wild-type littermates, was enhanced 3 h after a single injection of D. alpha (25 microg/kg, i.p.). Improved NORT performance was accompanied by elevated NADPH diaphorase staining in the ventral hippocampus as well as medial and cortical aspects of the amygdala, indicative of increased nitric oxide synthase (NOS) activity in these structures. NOS generates the intracellular messenger nitric oxide (NO) implicated in learning and memory. In keeping with this hypothesis, D. alpha significantly increased NO metabolite levels (nitrate and nitrite, NOx) in the hippocampus of both wild-type and STOP null mice. The NOS inhibitor, N (G)-nitro-L- arginine methyl ester (L-NAME; 25 mg/kg, i.p.), completely reversed the increase in hippocampal NOx levels produced by D. alpha. Moreover, L-NAME also inhibited the ability of D. alpha to improve the NORT performance of STOP null mice. Taken together, these observations suggest D. alpha enhances the NORT performance of STOP null mice by increasing production of NO.

Nitric-oxide synthase mediates the ability of darbepoetin alfa to attenuate pre-existing spatial working memory deficits in rats subjected to transient global ischemia.

Erythropoietin has been reported to improve the behavioral performance of healthy mice in tests thought to depend on synaptic plasticity in the CA1 region of the hippocampus. We show here for the first time that a single injection of the erythropoietin analog darbepoetin alfa reverses pre-existing cognitive deficits in adult rats that had been subjected to transient global ischemia produced by four-vessel occlusion (4-VO). Quantification of neuronal density demonstrated that 12 min of 4-VO selectively killed more than 90% of CA1 neurons in the dorsal hippocampus. Rats that had sustained a bilateral loss of hippocampal CA1 neurons in this range (4-VO rats) displayed more errors and longer escape latencies in the Barnes maze compared with sham-operated controls. A single injection of darbepoetin alfa (5000 U/kg i.p.) 4 h before behavioral testing decreased deficits in escape latency for 4-VO rats but not sham-operated controls. This improvement in spatial working memory performance was correlated with increased levels of nitric-oxide metabolites in the ventral hippocampus. Systemic administration of the nitric-oxide synthase inhibitor N(G)-nitro-L-nitro-arginine methyl ester reversed the increase in nitric-oxide metabolites and improvements in spatial working memory produced by darbepoetin alfa (5000 U/kg, i.p.) at a dose (10 mg/kg, i.p.) that did not impair the spatial working memory performance of intact rats. Taken together, these findings suggest that darbepoetin alfa reverses pre-existing spatial working memory deficits resulting from transient global ischemia by increasing the activity of nitric-oxide synthase, an enzyme implicated in synaptic plasticity.

MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and neurotoxicity of oxidized purine nucleotides.

In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase, efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2'-deoxy-8-oxoguanosine triphosphate (8-oxo-dGTP) and 2'-deoxy-2-hydroxyadenosine triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation into DNA or RNA. MTH1 is expressed in postmitotic neurons as well as in proliferative tissues, and it is localized both in the mitochondria and nucleus, thus suggesting that MTH1 plays an important role in the prevention of the mutagenicity and cytotoxicity of such oxidized purines as 8-oxoG which are known to accumulate in the cellular genome. Our recent studies with MTH1-deficient mice or cells revealed that MTH1 efficiently minimizes accumulation of 8-oxoG in both nuclear and mitochondrial DNA in the mouse brain as well as in cultured cells, thus contributing to the protection of the brain from oxidative stress.

MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity.

Enhanced oxidative stress has been implicated in the excitotoxicity of the CNS, and 8-oxo-7,8-dihydro-guanine (8-oxoG), a major type of oxidative damage in nucleic acids, was reported to be accumulated in the rat hippocampus after kainate administration. We herein showed that the 8-oxoG levels in mitochondrial DNA and cellular RNA increased significantly in the CA3 subregion of the mouse hippocampus 6-12 h after kainate administration but returned to basal levels within a few days. Laser-scanning confocal microscopy revealed the 8-oxoG accumulation in mitochondrial DNA to be remarkable in CA3 microglia, whereas that in nuclear DNA or cellular RNA was also detected in the CA3 pyramidal cells and astrocytes. 8-oxoG accumulation in cellular DNA or RNA should be suppressed by MutT homolog 1 (MTH1) with 8-oxo-dGTPase (8-oxo-7,8-dihydro-2'-deoxyguanosine triphosphatase) activity and 8-oxoG-DNA glycosylase 1 (OGG1) with 8-oxoG DNA glycosylase activity. We thus examined the expression level of MTH1 and OGG1 in the mouse hippocampus after kainate administration. The Mth1 mRNA level decreased soon after kainate administration and then quickly recovered beyond the basal level, and a continuously increased MTH1 protein level was observed, whereas the Ogg1 mRNA level remained constant. MTH1-null and wild-type mice exhibited a similar degree of CA3 neuron loss after kainate administration; however, the 8-oxoG levels that accumulated in mitochondrial DNA and cellular RNA in the CA3 microglia significantly increased in the MTH1-null mice in comparison with wild-type mice, thus demonstrating that MTH1 efficiently suppresses the accumulation of 8-oxoG in both cellular DNA and RNA in the hippocampus, especially in microglia, caused by excitotoxicity.