Recent findings with animal models have suggested a possible role for brain-derived neurotrophic factor (BDNF) in depression. We have therefore hypothesized that depression could be characterized by low levels of serum BDNF. Major depressed patients (15F + 15M) diagnosed according to DSM-IV criteria and healthy controls (15F + 15M) participated in the study. Serum BDNF was assayed with the ELISA method and the severity of depression was evaluated with Montgomery-Asberg-Depression Rating Scale (MADRS). BDNF levels were significantly lower in patients than in controls: 22.6 +/- 3 and 26.5 +/- 7 ng/ml (t-test = 2.7; d.f. = 58; P < 0.01). They were negatively correlated to the MADRS scores (r = -0.55; P < 0.02). Female patients were more depressed and released less BDNF than men. Analysis of covariance (MADRS and gender as independent variable vs. BDNF as dependent variable) indicated that depression severity mainly accounted for the negative correlation. These results suggest that major depression is characterized by low serum BDNF levels and support the hypothesis of neurotrophic factor involvement in affective disorders.

Decreased serum brain-derived neurotrophic factor levels in major depressed patients.

It is widely accepted that neuronal activity plays a pivotal role in synaptic plasticity. Neurotrophins have emerged recently as potent factors for synaptic modulation. The relationship between the activity and neurotrophic regulation of synapse development and plasticity, however, remains unclear. A prevailing hypothesis is that activity-dependent synaptic modulation is mediated by neurotrophins. An important but unresolved issue is how diffusible molecules such as neurotrophins achieve local and synapse-specific modulation. In this review, I discuss several potential mechanisms with which neuronal activity could control the synapse-specificity of neurotrophin regulation, with particular emphasis on BDNF. Data accumulated in recent years suggest that neuronal activity regulates the transcription of BDNF gene, the transport of BDNF mRNA and protein into dendrites, and the secretion of BDNF protein. There is also evidence for activity-dependent regulation of the trafficking of the BDNF receptor, TrkB, including its cell surface expression and ligand-induced endocytosis. Further study of these mechanisms will help us better understand how neurotrophins could mediate activity-dependent plasticity in a local and synapse-specific manner.

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BDNF and activity-dependent synaptic modulation.

Profound neuronal dysfunction in the entorhinal cortex contributes to early loss of short-term memory in Alzheimer's disease. Here we show broad neuroprotective effects of entorhinal brain-derived neurotrophic factor (BDNF) administration in several animal models of Alzheimer's disease, with extension of therapeutic benefits into the degenerating hippocampus. In amyloid-transgenic mice, BDNF gene delivery, when administered after disease onset, reverses synapse loss, partially normalizes aberrant gene expression, improves cell signaling and restores learning and memory. These outcomes occur independently of effects on amyloid plaque load. In aged rats, BDNF infusion reverses cognitive decline, improves age-related perturbations in gene expression and restores cell signaling. In adult rats and primates, BDNF prevents lesion-induced death of entorhinal cortical neurons. In aged primates, BDNF reverses neuronal atrophy and ameliorates age-related cognitive impairment. Collectively, these findings indicate that BDNF exerts substantial protective effects on crucial neuronal circuitry involved in Alzheimer's disease, acting through amyloid-independent mechanisms. BDNF therapeutic delivery merits exploration as a potential therapy for Alzheimer's disease.

/pdf/neuroprotective-effects-of-brain-derived-neurotrophic-factor-wkzrc23dcb.pdf

Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease

Brain-derived neurotrophic factor in the control human brain, and in Alzheimer's disease and Parkinson's disease.

Kindling and status epilepticus models of epilepsy: rewiring the brain.

Brain-derived neurotrophic factor is reduced in Alzheimer's disease.

Differential regulation by MK801 of immediate-early genes, brain-derived neurotrophic factor and trk receptor mRNA induced by a kindling after-discharge.

The aim of the present study was to investigate the expression of the neurotrophin, brain-derived neurotrophic factor (BDNF), in the vestibular nucleus complex (VNC) following unilateral vestibular deafferentation (UVD) Using immunohistochemistry, BDNF expression was analyzed in the bilateral VNC of the guinea pig in sham animals, and immediately, 10 h, and 50 h post-UVD No BDNF expression was seen in the VNC in sham animals or immediately or 10 h post-UVD However, at 50 h post-UVD, clear BDNF expression was seen in the bilateral lateral vestibular nuclei (LVN) and in the bilateral abducens nuclei, but not in the medial vestibular nuclei (MVN) The significance of this late BDNF expression is nuclear

Unilateral Vestibular Deafferentation Induces Brain-Derived Neurotrophic Factor (BDNF) Protein Expression in the Guinea Pig Lateral but not Medial Vestibular Nuclei

Qiao Yan

Papers

Brain-derived neurotrophic factor is reduced in Alzheimer's disease.

Differential regulation by MK801 of immediate-early genes, brain-derived neurotrophic factor and trk receptor mRNA induced by a kindling after-discharge.

Unilateral Vestibular Deafferentation Induces Brain-Derived Neurotrophic Factor (BDNF) Protein Expression in the Guinea Pig Lateral but not Medial Vestibular Nuclei