Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets

Author(s):

Ji-chun Zhang, Wei Yao and Kenji HashimotoPages 1-10 (10)

Abstract:

Depression is the most prevalent and among the most debilitating of psychiatric disorders. The precise neurobiology of this illness is unknown. Several lines of evidence suggest that peripheral and central inflammation plays a role in depressive symptoms, and that anti-inflammatory drugs canimprove depressive symptoms in patients with inflammation-related depression. Signaling via brain-derived neurotrophic factor (BDNF) and its receptor, tropomycin receptor kinase B (TrkB) plays a key role in the pathophysiology of depression and in the therapeutic mechanisms of antidepressants. A recent paper showed that lipopolysaccharide (LPS)-induced inflammation gave rise to depression-like phenotype by altering BDNF-TrkB signaling in the prefrontal cortex, hippocampus, and nucleus accumbens, areas thought to be involved in the antidepressant effects of TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF) and TrkB antagonist, ANA-12.Here we provide an overview of the tryptophan-kynurenine pathway and BDNF-TrkB signaling in the pathophysiology of inflammation-induced depression, and propose mechanistic actions for potential therapeutic agents.Additionally, the authors discuss the putative role ofTrkB agonists and antagonists as novel therapeutic drugs for inflammation-related depression.

Keywords:

Brain-derived neurotrophic factor (BDNF); Depression;Hippocampus, Inflammation;Nucleus accumbens; Prefrontal cortex; TrkB

Affiliation:

Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan

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Animal Models of Maternal Immune Activation in Depression Research

Author(s):

Marianne Ronovsky, Stefanie Berger, Barbara Molz, Angelika Berger and Daniela D. PollakPages 1-16 (16)

Abstract:

Background: Depression and schizophrenia are debilitating mental illnesses with significant socio-economic impact. The high degree of comorbidity between the two disorders, shared symptoms and risk factors, suggest partly common pathogenic mechanisms. Supported by human and animal studies, maternal immune activation (MIA) has been intimately associated with the development of schizophrenia. However, the link between MIA and depression has remained less clear, in part due to the lack of appropriate animal models. Objective: Here we aim to summarize findings obtained from studies using MIA animal models and discuss their relevance for preclinical depression research. Methods: Results on molecular, cellular and behavioral phenotypes in MIA animal models were collected by literature search (PubMed) and evaluated for their significance for depression. Results: Several reports on offspring depression-related behavioral alterations indicate an involvement of MIA in the development of depression later in life. Depression-related behavioral phenotypes were frequently paralleled by neurogenic and neurotrophic deficits and modulated by several genetic and environmental factors. Conclusion: Literature evidence analyzed in this review supports a relevance of MIA as animal model for a specific early life adversity, which may prime an individual for the development of distinct psychopathologies later life. MIA animal models may present a unique tool for the identification of additional exogenous and endogenous factors, which are required for the determination of a specific neuropsychiatric disorder, such as depression, later in life. Hereby, novel insights into the molecular mechanism involved in the pathophysiology of depression may be obtained, supporting the identification of alternative therapeutic strategies.

Affiliation:

Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria

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Freezing of Gait in Parkinsonism and its Potential Drug Treatment

Author(s):

Li-Li Zhang, S. Duff Canning and Xiao-Ping WangPages 302-306 (5)

Abstract:

Freezing of gait (FOG) is a heterogeneous symptom. Studies of treatment for FOG are scarce. Levodopa and monoamine oxidase inhibitors (rasagiline and selegiline) have shown effective improvement for FOG. Other drugs, such as L-threo-3, 4-dihydroxyphenylserine, amantadine, and botulinum toxin have exhibited some beneficial effects. The present review summarizes the potential drug treatment for FOG in Parkinsonism.

Keywords:

Drug treatment, freezing of gait, Levodopa, Parkinson’s disease, Parkinsonism.

Affiliation:

Department of Neurology, Shanghai First People’s Hospital, Shanghai Jiao-Tong University, China. 200080.

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Drug Therapy for Behavioral and Psychological Symptoms of Dementia

Author(s):

Feng Wang, Ting-Yi Feng, Shilin Yang, Maurice Preter, Jiang-Ning Zhou and Xiao-Ping WangPages 307-313 (7)

Abstract:

Dementia, which can be induced by diverse factors, is a clinical syndrome characterized by the decline of cognitive function. Behavioral and psychological symptoms of dementia (BPSD) include depression, agitation, and aggression. Dementia causes a heavy burden on patients and their caregivers. Patients with BPSD should be assessed comprehensively by practitioners and offered appropriate non-pharmacologic and pharmacologic therapy. Nonpharmacologic therapy has been recommended as the basal treatment for BPSD; however, pharmacologic therapy is required under many situations. Medications, including antipsychotic agents, antidepressants, sedative and hypnotic agents, mood stabilizers, cholinesterase inhibitors, and amantadine, are extensively used in clinical practice. We have reviewed the progression of pharmacologic therapy for BPSD.

Keywords:

Alzheimer’s disease, antipsychotic, behavioral and psychological symptoms of dementia, dementia, drug, psychiatric symptoms.

Affiliation:

Department of Neurology, Shanghai First People’s Hospital, Shanghai Jiao-Tong University, China, 200080.

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Current Therapy of Drugs in Amyotrophic Lateral Sclerosis

Author(s):

Haiyan Lu, Wei Dong Le, Ya-Ying Xie and Xiao-Ping WangPages 314-321 (8)

Abstract:

Amyotrophic lateral sclerosis (ALS), commonly termed as motor neuron disease (MND) in UK, is a chronically lethal disorder among the neurodegenerative diseases, meanwhile. ALS is basically irreversible and progressive deterioration of upper and lower motor neurons in the motor cortex, brain stem and medulla spinalis. Riluzole, used for the treatment of ALS, was demonstrated to slightly delay the initiation of respiratory dysfunction and extend the median survival of patients by a few months. In this study, the key biochemical defects were discussed, such as: mutant Cu/Zn superoxide dismutase, mitochondrial protectants, and anti-excitotoxic/ anti-oxidative / antiinflammatory/ anti-apoptotic agents, so the related drug candidates that have been studied in ALS models would possibly be further used in ALS patients.

Keywords:

Amyotrophic lateral sclerosis, motor neuron disease, neurodegenerative disease, SOD1 mutations, riluzole, edaravone, pyrimethamine.

Affiliation:

Department of Neurology, Shanghai First People’s Hospital , Shanghai Jiao-Tong University, China, 200080.

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