Microglia, major sources of free radicals and inflammatory cytokines, play crucial roles in brain homeostasis and various brain pathologies such as neurodegenerative diseases and neuropathic pain. Recent postmortem and imaging studies have indicated microglial activation in the brain of schizophrenic patients and patients who committed suicide. We have recently demonstrated that some kinds of antipsychotics and antidepressants such as selective serotonin reuptake inhibitors(SSRIs)significantly inhibit the release of nitric oxide and proinflammatory cytokines from activated microglia in vitro. Based on these results, we put forward a novel neuro-immunological hypothesis of psychiatric diseases via microglia. Microglia may play an important role in various psychiatric diseases by modulating inflammatory/immunological environments through moving around dynamically and releasing chemical mediators in the CNS. Our hypothesis shed new light on a novel therapeutic strategy for psychiatric diseases. Furthermore, microglia might be a key player in human mental activities, especially 'unconscious drives', from the standpoint of psychodynamic psychiatry. Microglia research has the potential to bridge the huge gap between biological psychiatry and psychoanalysis.

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Brain-derived neurotrophic factor (BDNF) is involved in neuronal proliferation, differentiation and survival during development. BDNF and its tyrosine kinase receptor (TrkB) are expressed in hypothalamic nuclei associated with eating behaviours. Furthermore, mice heterozygous for the BDNF gene exhibit hyperactivity and higher levels of anxiety in response to stress. The aetiology of eating disorders (ED) is complex and evidence indicates that both biological/genetic and psychosocial factors are involved. We investigated serum brain-derived neurotrophic factor (BDNF) in individuals with current anorexia nervosa (AN), bulimia nervosa (BN) and those recovered from AN. Serum BDNF concentrations in the AN group and those in the BN group were significantly lower compared to the HC group. Serum BDNF concentrations in the AN group were significantly lower compared to the ANRec group. We proposed that serum BDNF may be a biological marker for eating-related psychopathology and of recovery in AN.

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Systemic lupus erythematosus (SLE) is a chronic, multisystemic, autoimmune disease that may involve the central, peripheral, and autonomic nervous systems and can present with a wide variety of neurological and psychiatric manifestations. However, there are few biomarkers which always reflect the severity of the psychiatric symptoms with SLE. In this review, recent advances in the pathogenesis and biomarkers of neuropsychiatric systemic lupus erythematosus (NPSLE) were outlined.

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Since 1985, an accurate cohort study of dementia has been going on in the town of Hisayama, Japan. When compared the results of four cross-sectional examinations of dementia conducted from 1985 to 2005 on Hisayama residents aged 65 years or older, the prevalence of Alzheimer's disease (AD) significantly increased with time. The prevalence of vascular dementia (VaD) decreased in the early period and then increased in the late period. Among subjects developing dementia in a cohort study on the elderly Hisayama residents without dementia, the most frequent type of dementia was AD, followed by VaD and mixed type of dementia in descending order, and 86% of all dementia cases developed were attributable to AD or VaD. We revealed the significant associations between glucose intolerance/diabetes and the risks of both VaD and AD, while hypertension was a significant risk factor for the development of VaD but not for AD. In a pathological study of Hisayama residents, higher levels of 2-hour post-load plasma glucose, fasting insulin, and HOMA-IR were significantly associated with increased risk of neuritic plaques. Clinical and experimental evidence has indicated that glucose intolerance and diabetes induce dementia through various mechanisms such as atherosclerosis, microvascular disease, glucose toxicity, and impaired insulin metabolism.

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Induced pluripotent stem (iPS) cell technology shows great potential for the study of pathogenesis, and drug discovery toward neurodegenerative diseases. This review summarizes the current status on the neurodegenerative disease-specific iPS cell research and describes its potential.

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Visualization of amyloid fibrils by in-vivo imaging techniques accordingly offers diagnostic information at a prodromal stage of the disease, and facilitates therapeutic evaluations during the course of emerging anti-amyloid treatments. By comparing findings in positron emission tomographic (PET) amyloid imaging of AD and model mouse brains, an N-terminally cleaved and modified Aβ termed AβN3 (pE) has been identified as a major constituent of “AD-like” Aβ plaques enriched with binding sites for imaging agents. Clarification of the molecular pathogenesis and development of diagnostic and therapeutic agents can synergistically promote each other with the aid of molecular imaging technologies. Other elements such as tau inclusions and activated microglia in living brains would be of vital significance.

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Frontotemporal lobar degeneration (FTLD) is a clinical syndrome characterized by behavioral and language difficulties, which refers to a clinically, genetically, and neuropathologically heterogeneous group of neurodegenerative disorders. Familial FTLD has been linked to mutations in several genes: the microtubule-associated protein tau (MAPT) , progranulin (GRN) , valosin-containing protein (VCP) and charged multivescicular body protein 2B (CHMP2B) , and genetic locus on chromosome 9p linked to familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The associated neuropathology is characterized by selective degeneration of the frontal and temporal lobes with the neuronal and/or glial inclusions. The current classification of FTLD neuropathology is based on the major constituent protein of them : tau, TAR DNA-binding protein of 43 kD (TDP-43) , and fused in sarcoma (FUS) . Abnormal phosphorylation, ubiquitination, and proteolytic cleavage are the common pathologic signature of tau and TDP-43 accumulated in diseased brains. Recent findings of TDP-43 and FUS reveal that FTLD and ALS share a common mechanism of pathogenesis. This review focuses on the current understanding of the molecular neuropathology of FTLD, and their relevance to the development of the therapeutics.

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