ABSTRACT
The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are important mediators of brain and neuronal development, the maintenance of homeostatic conditions in the adult nervous system, and the complex interplay of central and peripheral physiological and pathophysiological factors. To date there are few studies examining blood concentrations of neurotrophic factors in large samples of healthy and diseased individuals and no published study specifically addresses peripheral BDNF and NGF levels in late life. Using improved highly sensitive and specific fluorometric two-site enzyme-linked immunosorbent assays we examined BDNF (n=465) and NGF (n=175) serum levels in a large cohort of elderly individuals (age range: 70-103 years). Neither BDNF nor NGF serum levels proved to be normally distributed, indicating that previously published studies with small sample sizes using parametric testing may be misleading. A significant correlation was found between BDNF and platelet count (r=0.344, p<0.01), age and BDNF protein (r=-0.101, p=0.029) and BDNF and NGF serum levels (r=0.152, p=0.04). No other major influencing factors were found including gender, depression, and dementia.
Subject(s)
Blood Platelets/metabolism , Brain-Derived Neurotrophic Factor/blood , Geriatric Assessment , Nerve Growth Factor/blood , Age Factors , Aged , Aged, 80 and over , Humans , Sex Characteristics , Statistics as Topic , Statistics, Nonparametric , Time FactorsABSTRACT
Previous studies found an elevation of the dopamine D3 receptor (DRD3) mRNA as determined in peripheral lymphocytes in schizophrenic patients. The aim of this study was to test the hypothesis of elevated DRD3 mRNA in schizophrenia compared to bipolar disorder. Twenty-four patients, 13 schizophrenic and 11 bipolar, were included according to DSM-IV criteria. Psychometric measures were conducted using the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, Montgomery-Asberg Depression Rating Scale and Young Mania Rating Scale. mRNA was isolated from lymphocytes of venous blood samples and DRD3 mRNA was quantified using real-time reverse transcription PCR. We found a decrease in DRD3 mRNA in 13 schizophrenic (p = 0.009) and 11 bipolar (p = 0.023) patients as compared to controls. Medication history and severity of positive symptoms did not significantly influence DRD3 expression. Higher levels of DRD3 mRNA were correlated with negative schizophrenic symptoms. Interestingly, after treatment of patients with antipsychotics, DRD3 mRNA levels increased to similar levels as those of healthy controls. Bipolar patients, however, showed a slower increase in DRD3 mRNA levels after 3 weeks of therapy. Our findings suggest that the expression of DRD3 mRNA is reduced in schizophrenia and bipolar disorder, supporting the hypothesis of distorted homeostasis of dopamine receptor subtypes in psychotic disorder. The observed diminution was not specific for schizophrenia but also for bipolar disorder requiring further analysis of the regulatory factors involved in dopamine receptor subtype expression.
Subject(s)
Bipolar Disorder/metabolism , Receptors, Dopamine D2/metabolism , Schizophrenia/metabolism , Adolescent , Adult , Antipsychotic Agents/therapeutic use , Bipolar Disorder/classification , Bipolar Disorder/drug therapy , Bipolar Disorder/genetics , Cloning, Molecular/methods , Female , Gene Expression Regulation/drug effects , Humans , Male , Middle Aged , RNA, Messenger/metabolism , Receptors, Dopamine D2/genetics , Receptors, Dopamine D3 , Reverse Transcriptase Polymerase Chain Reaction/methods , Schizophrenia/classification , Schizophrenia/drug therapy , Schizophrenia/genetics , Sequence Analysis, DNA/methods , Statistics, NonparametricABSTRACT
OBJECTIVE: Nerve growth factor is important for the development and function of the cholinergic basal forebrain. The authors examined the hypothesis that the concentration of nerve growth factor is lower than normal in the preclinical phase of neurodegenerative dementia, especially Alzheimer's disease. METHOD: The serum nerve growth factor concentration of subjects from the Berlin Aging Study and the Berlin Memory Clinic who later developed Alzheimer's disease were compared with those of subjects who were free of dementia and subjects who were already suffering from Alzheimer's disease. RESULTS: There were 17 subjects in each group, matched for age and sex. The three groups differed in log-10-transformed mean nerve growth factor concentrations: 1.62 (SD=0.59) for the healthy comparison subjects, 0.92 (SD=0.30) for the subjects with preclinical dementia, and 1.44 (SD=0.61) for the subjects with Alzheimer's disease. CONCLUSIONS: These results support the hypothesis of disturbed nerve growth factor regulation in the serum of patients with preclinical Alzheimer's disease. Mechanisms by which these disturbances appear are unclear, but they may reflect the situation in the preclinical Alzheimer's disease brain.
